Alcohol use disorder

General Information
Description:
 alcohol use disorder may describe alcohol abuse, alcohol dependence, or hazardous drinking
Also called:
 alcoholism
Definitions:
 alcohol misuse - spectrum of behaviors including risky or hazardous use(3)
o risky or hazardous alcohol use
 drinking more than recommended daily, weekly, or per-occasion amount resulting in
increased risk for health consequences
 for men, > 14 drinks per week or > 4 drinks per occasion
 for women, > 7 drinks per week or > 3 drinks per occasion
o alcohol abuse - continued drinking despite adverse consequences
 drinking that leads individual to recurrently fail in major home, work, or school responsibilities
 using alcohol in physically hazardous situations (such as operating heavy machinery)
 having alcohol-related legal or social problems
o alcohol dependence (alcoholism)
 physical cravings and withdrawal symptoms
 frequent consumption of alcohol in larger amounts than intended over longer periods
 need for markedly increased amounts of alcohol to achieve intoxication
 DynaMed commentary -- alcoholism is an imprecise term, the term can make some patients defensive,
and is probably best used only with patients who self-identify as alcoholics
 alcohol dependence subtypes
o 31% young adult -- characterized by periodic heavy drinking and relatively low rates of
comorbidity
o 21% young antisocial -- early onset of drinking and alcohol use disorder, higher rates of
comorbidities (personality disorders, depression, other substance use disorders)
o 19% functional -- more often employed and socially stable than other subtypes
o 19% intermediate familial -- intermediate between functional and chronic severe subtypes
o 9% chronic severe -- likely to fit stereotypical picture of "alcoholic"
o Reference - Drug Alcohol Depend 2007 Dec 1;91(2-3):149 full-text
 alcohol dependence may occur without alcohol abuse
o based on national United States survey with 42,392 face-to-face interviews
o among participants meeting DSM-IV criteria for alcohol dependence, 34% (29% of men, 46% of
women) did not meet criteria for alcohol abuse
o Reference - Arch Gen Psychiatry 2004 Sep;61(9):891 full-text
 "standard drink" or "unit" drink varies by country, sample amounts include
o United Kingdom - 8 g
o United States - 12 to 14 g (12 ounces beer, 4-5 oz glass of wine, 1-1.5 ounces distilled spirits)
o Japan - 19.75 g
o Reference - Alcohol Res Health 2003;27(1):18 EBSCOhost Full Text PDF
o see DynaMed Calculator for Standard Drink Equivalents
Epidemiology
Who is most affected:
 binge drinking in United States most common in
o men
o persons aged 18-34 years
o persons of white race
o those with household income < $25,000 after adjusting for sex and age
o Reference - MMWR Morb Mortal Wkly Rep 2009 Apr 3;58(12):301 EBSCOhost Full Text full-
text
  alcohol use disorder can occur in adolescence
o based on sample of 15,349 high school students (1999 Youth Risk Behavior Survey)
o 50% United States children aged 12-20 years old drink
o Reference - JAMA 2003 Feb 26;289(8):989, correction can be found in JAMA 2003 Apr
9;289(14):1782, editorial can be found in JAMA 2003 Feb 26;289(8):1031
Incidence/Prevalence:
 8.5% prevalence of alcohol use disorder in past year in adults in United States
o national survey with 43,093 face-to-face interviews with representative sample of United States
adults
o 8.5% of United States adults met DSM-IV criteria for current (that is, past year) alcohol use
disorder
 4.7% met criteria for alcohol abuse
 3.8% met criteria for alcohol dependence
o 30.3% of United States adults met DSM-IV criteria for lifetime alcohol use disorder
 17.8% met criteria for alcohol abuse
 12.5% met criteria for alcohol dependence
o only 24.1% with alcohol dependence ever treated
o Reference - Arch Gen Psychiatry 2007 Jul;64(7):830
 15% of United States adults meet the Centers for Disease Control and Prevention (CDC) criterion for
hazardous drinking, > 5 drinks on one occasion in the past 30 days in a population-based survey
(Behavioral Risk Factor Surveillance System Prevalence Data 1999)
 binge drinking very common among United States adults and adolescents
o based on cross-sectional study in 2009
o self-reported binge drinking in adults ranged from 15.2% (those responding by landline phone) to
20.6% (those responding by cellular phone)
o binge drinking most common in men (20.7%), persons aged 18-34 years (25.6%-22.5%), those
of white race (16%), and persons with annual household incomes ≥ $75,000 (19.3%)
o prevalence in high school students 24.2%
o Reference - MMWR Morb Mortal Wkly Rep 2010 Oct 8;59(39):1274 EBSCOhost Full
Text full-text
o estimated mean 7 binge drinking episodes per person/year in annual surveys 1993-2001 (JAMA
2003 Jan 1;289(1):70, commentary can be found in JAMA 2003 Apr 2;289(13):1635
 estimated 51.5% of nonpregnant women and 7.6% of pregnant women report alcohol use
in United States
o based on self-reported data from CDC from 2006 to 2010
o binge drinking reported by 15% of nonpregnant women and 1.4% of pregnant women
o highest rates of alcohol use in pregnant women reported by those aged 35-44 years (14.3%), of
white race (8.3%), college graduates (10%), or employed (9.6%)
o Reference - MMWR Morb Mortal Wkly Rep 2012 Jul 20;61:534 EBSCOhost Full Text full-text
 alcohol use disorder common, harmful or hazardous use even more common
o cross-sectional survey of 300 patients > 18 years old with scheduled appointments at a hospital-
based outpatient clinic that is the primary teaching site for a family practice residency program in
the Northeast United States
o only 300 of 1,021 potentially eligible patients were interviewed so selection bias may alter results
o 17.7% lifetime prevalence of DSM-IV criteria for abuse or dependence
o 49.3% had at least one symptom of harmful or hazardous use during their lifetime
o Reference - Arch Fam Med 2000 Sep-Oct;9(9):814 full-text
 alcohol use and misuse common in Canada
o based on 2005 Canadian Addiction Survey
o 79.3% persons > 15 years old consume alcohol
o 17% current alcohol drinkers engage in hazardous drinking behaviors (8.9% women) in 2005
o 1,631 persons < 69 years old died of chronic disease attributed to alcohol consumption in 2003,
or 2.4% of deaths in this age group
 this does not include deaths due to trauma
o Reference - CMAJ 2007 Feb 27;176(5):621 full-text, Canadian Addiction Survey PDF, commentary
can be found in CMAJ 2007 Jul 3;177(1):65 full-text
 unhealthy drinking patterns common (about 10%) in elderly
 o based on cross-sectional survey of 12,413 community-dwelling Medicare beneficiaries > 65 years
old
o unhealthy drinking pattern defined as any of
 > 30 drinks/month
 > 3 drinks on any day
o prevalence of unhealthy drinking
 16% men
 4% women
o Reference - J Am Geriatr Soc 2008 Feb;56(2):214 EBSCOhost Full Text, commentary can be
found in J Am Geriatr Soc 2008 Sep;56(9):1769 EBSCOhost Full Text
 7.4% prevalence of DSM-IV alcohol use disorders in acute care hospitalizations
o based on study of 2,040 admissions in 90 United States nonfederal short-stay general hospitals
o prevalence 11.1% in men and 4.2% in women
o Reference - Arch Intern Med 2003 Mar 24;163(6):713
 7.4% prevalence of alcoholism in study of hospitalized patients
o based on 1-day study of 795 adult inpatients in 2 Midwestern teaching hospitals
o 667 (84%) responded
o 569 completed self-administered alcoholism screening test of whom 42 (7.4%) has score
identified as alcohol dependent
o Reference - Mayo Clin Proc 2001 May;76(5):460, editorial can be found in Mayo Clin Proc 2001
May;76(5):457
 almost half of United States high school students report drinking alcohol
o 44.9% high school students reported drinking alcohol during past month (28.8% reported binge
drinking) in 2003 National Youth Risk Behavior Survey (Pediatrics 2007 Jan;119(1):76),
commentary can be found in Pediatrics 2007 May;119(5):1035
o adolescents (high school students) in New Hampshire (United States) reported 47% rate of
alcohol use and 30.6% reported binge drinking in 2003; adults in New Hampshire in 2001
reported 15.8% rate of binge drinking and 6.3% rate of heavy drinking (MMWR Morb Mortal Wkly
Rep 2004 Mar 5;53(8):174 EBSCOhost Full Text full-text)
o current alcohol use reported in 38% of high school students in Georgia in 2007
 based on 2007 Georgia Youth Risk Behavior Survey
 binge drinking in past 30 days reported in 19%
 in students reporting current alcohol use
 usual alcohol consumed was liquor in 44%
 usual location of consumption at another's home in 58%
 usual source was someone giving them alcohol in 37%
 Reference - MMWR Morb Mortal Wkly Rep 2009 Aug 21;58(32):885 EBSCOhost Full
Text full-text
 rate of unintentional poisoning mortality attributed to alcohol in United States per 100,000 population
was 0.1 in 1999 and 0.1 in 2004 (MMWR Morb Mortal Wkly Rep 2007 Feb 9;56(5):93 EBSCOhost
Full Text full-text)
 11.7% of all documented deaths in American Indian and Alaska Natives attributable to alcohol in 2001-
2005 (MMWR Morb Mortal Wkly Rep 2008 Aug 29;57(34):938 EBSCOhost Full Text full-text)
 about 75,776 deaths and 2.3 million years of potential life lost attributed to excessive alcohol use in
United States in 2001 (MMWR Morb Mortal Wkly Rep 2004 Sep 24;53(37):866 EBSCOhost Full
Text full-text)
 lifetime risk of alcohol dependence (DSM-IV criteria) estimated to be 28.8% in adult first-
degree relatives of persons with alcohol dependence and 14.4% in controls
o based on study of 8,296 first-degree relatives and 1,654 controls
o corresponding rates were 37% and 20.5% using DSM-III-R criteria
o Reference - Arch Gen Psychiatry 2004 Dec;61(12):1246
 hazardous drinking may account for half of deaths in working age men in Russia
o based on case-control study
o cases were all 2,835 men aged 25-54 years who died while living in Izhevsk, Russia
o 3,078 controls were randomly selected from city population and frequency matched to age of
death
 o interviews with proxy informants living in same household obtained from 62% cases and 57%
controls
o complete information obtained for 1,468 cases and 1,496 controls
o 51% cases vs. 13% controls classed as problem drinkers or drank non-beverage alcohol
(manufactured ethanol-based liquids not intended to be drunk)
o 43% of deaths were attributable to beverage or non-beverage ethanol
o Reference - Lancet 2007 Jun 16;369(9578):2001, editorial can be found in Lancet 2007 Jun
16;369(9578):1975, commentary can be found in Lancet 2007 Aug 18;370(9587):561
Likely risk factors:
 alcohol dependence reported to have substantial heritable basis
o based on classic twin study with 3,372 twin pairs
o Reference - Arch Gen Psychiatry 2004 Sep;61(9):897
 problematic alcohol use during adolescence associated with increased risk for adult
alcohol use disorder, substance use disorder, depression and antisocial personality
disorder symptoms
o based on study of 940 persons interviewed at age 14-18 years and again at age 24 years
o other factors during adolescence that increased risk for adult alcohol use disorder were daily
smoking, conduct/oppositional defiant disorder and father with alcohol use disorder
o Reference - J Am Acad Child Adolesc Psychiatry 2001 Jan;40(1):83 in Pediatric Notes 2001 Feb
15;25(7):25
 starting drinking before age 14 years associated with higher likelihood of alcohol
dependence compared to starting drinking after age 21 years
o based on survey of 43,093 adults
o Reference - Arch Pediatr Adolesc Med 2006 Jul;160(7):739
Possible risk factors:
 bariatric surgery associated with increased risk of alcohol use disorder
o based on prospective cohort study
o 1,945 adults (mean age 47 years, 79% female, 87% white) having bariatric surgery in United
States completed preoperative and postoperative (at 1 year and/or 2 year) assessments
o 72% completed 2-year postoperative assessment
o prevalence of alcohol use disorder symptoms
 7.6% 1 year prior to surgery
 7.3% 1 year after surgery (not significant vs. 1 year prior to surgery)
 9.6% 2 years after surgery (p = 0.01 vs. 1 year prior to surgery)
o preoperative factors associated with increased risk of alcohol use disorder after bariatric surgery
included male gender, younger age, smoking, regular alcohol consumption (≥ 2 drinks/week),
alcohol use disorder, recreational drug use, lower sense of belonging, and having Roux-en-Y
gastric bypass procedure
o Reference - JAMA 2012 Jun 20;307(23):2516
 college students have increased risk of alcohol abuse
o based on cross-sectional study of 6,352 young adults aged 19-21 years in United States 2001
o 18% of United States college students (24% men, 13% women) and 15% of non-college-
attending peers (22% men, 9% women) had clinically significant alcohol-related problems in past
year
o college students more likely to have DSM-IV diagnosis of alcohol abuse but not DSM-IV alcohol
dependence
o Reference - Arch Gen Psychiatry 2005 Mar;62(3):321
 prenatal alcohol exposure associated with increased risk of drinking problems at age 21
years
o based on study of 433 subjects
o Reference - Arch Gen Psychiatry 2003 Apr;60(4):377
 past severe traumatic events associated with alcohol use disorders
o based on interviews of 432 American Indian adolescents and young adults
o number of traumas associated with increased risk in dose-dependent fashion
o Reference - J Trauma Stress 2006 Dec;19(6):937 EBSCOhost Full Text
 working > 48 hours/week associated with small increase in risky alcohol use
o based on pooled analysis of individual patient data from observational studies
 o systematic review of 61 published and nonpublished observational studies with data to assess
association between working hours and alcohol use in 333,693 individuals from 14 countries
o risky alcohol use defined as > 14 drinks/week in women and > 21 drinks/week in men
o compared to standard work week of 35-40 hours in analysis of individual patient data from 18
studies, increased risk of new-onset risky alcohol use associated with
 working ≥ 55 hours/week (adjusted odds ratio 1.13, 95% CI 1.02-1.26)
 working ≥ 49-54 hours/week (adjusted odds ratio 1.12, 95% CI 1.01-1.25)
o Reference - BMJ 2015 Jan 13;350:g7772 full-text
 combat exposure associated with increased risk of alcohol use problems in military
personnel
o based on cohort study of 48,481 active duty, Reserve or National Guard personnel
o military personnel with combat exposure reported increased rates of new-onset heavy weekly
drinking, binge drinking, and alcohol-related problems compared to non-deployed military
personnel
o increased risk also associated with younger age
o Reference - JAMA 2008 Aug 13;300(6):663, commentary can be found in JAMA 2008 Dec
10;300(22):2606
 use of alcohol to fall asleep associated with increased risk of hazardous drinking
o based on cross-sectional study of 1,984 patients answering primary care questionnaire
o Reference - Ann Fam Med 2010 Nov-Dec;8(6):484 EBSCOhost Full Text full-text
 depiction of alcohol use in movies associated with increased risk of adolescent binge
drinking
o based on cross-sectional study of 16,551 youth (mean age 13.4 years) from 6 European countries
o Reference - Pediatrics 2012 Apr;129(4):709
Associated conditions:
 smoking associated with alcohol misuse
o based on cross-sectional study
o 42,374 United States adults were assessed for alcohol and tobacco use in 2001-2002
o hazardous alcohol use defined as consuming more alcohol than is recommended by gender-
specific daily and weekly limits (> 14 drinks per week or > 5 drinks per day in men, and > 7
drinks per week or > 4 drinks per day in women)
o compared to never-smokers, daily, occasional and previous smoking associated with increased risk
of hazardous alcohol use
 daily smokers (odds ratio (OR) 3.23, 95% CI 3.02-3.46)
 occasional smokers (OR 5.33, 95% CI 4.7-6.04)
 previous (ex-smokers) (OR 1.19, 95% CI 1.1-1.28)
o Reference - Arch Intern Med 2007 Apr 9;167(7):716 full-text
 alcohol and drug use disorders strongly associated with personality disorders
o face-to-face interviews of 43,093 adults in national United States survey 2001-2002 which
evaluated DSM-IV criteria for alcohol and drug use disorders and 7 of 10 personality disorders
o 8.5% of United States adults had current alcohol use disorder, 2% had current drug abuse or
dependence, 14.8% had personality disorder
o at least 1 personality disorder was identified in 28.6% of persons with current alcohol use disorder
and 47.7% of persons with current drug use disorder
o among persons with at least 1 personality disorder, 16.4% had current alcohol use disorder and
6.5% had current drug use disorder; most strongly related personality disorders were antisocial,
histrionic and dependent
o Reference - Arch Gen Psychiatry 2004 Apr;61(4):361
 alcohol use disorder associated with increased risk for completed suicide
o based on prospective cohort study
o 18,146 individuals aged 20-93 years old were followed for 26 years
o alcohol use disorder associated with increased rate of completed suicides
 overall (hazard ratio [HR] 7.98, 95% CI 5.27-12.07) in analysis unadjusted for comorbid
psychiatric disorders
 after adjustment for comorbid psychiatric disorders (adjusted HR 3.23, 95% CI 1.96-5.33)
 in subgroup analysis of individuals without comorbid psychiatric disorders (adjusted HR 9.69,
95% CI 4.88-19.25)
 o Reference - Psychiatry Res 2009 May 15;167(1-2):123
 preteen alcohol use may be associated with violent behavior and suicide in adolescents
o based cross-sectional analysis
o 856 adolescents (all in seventh grade) who participated in youth violence survey were assessed
o 35% reported alcohol use initiation before 13 years old
o compared to peer nondrinkers preteen alcohol users were more likely to report
 dating violence (as perpetrators adjusted odds ratio [OR] 3.01 and as victims adjusted OR
2.86, p < 0.05)
 peer violence (as perpetrators adjusted OR 2.19 and as victims adjusted OR 1.9, p < 0.05)
 suicidal ideation (adjusted OR 4.02, p < 0.05)
 suicide attempts (adjusted OR 6.2, p < 0.05)
o Reference - Pediatrics 2008 Feb;121(2):297, commentary can be found in Pediatrics 2008
Jun;121(6):1287
History and Physical
History:
Chief concern (CC):
 screen all patients using one of following
o CAGE questions
o Alcohol Use Disorders Identification Test (AUDIT) questionnaire (see Project
Cork or AlcoholScreening.org for details)
o single question "When was the last time you had more than X drinks in one day?" where X = 4
for women, 5 for men
o see details under Screening below
 ask about pain, vomiting, bleeding
History of present illness (HPI):
 assess type and amount of alcohol, usual drinking pattern, frequency of heavy drinking (> 5 drinks
per occasion)
 other drug use - illicit drugs, tobacco, medications, herbal drugs
 complications of alcohol use
 history of withdrawal symptoms
 history of trauma - fights, motor vehicle crash
Physical:
General physical:
 breath odor, muscle wasting
Skin:
 spider angiomata, jaundice, signs of trauma
HEENT:
 nystagmus
 inspect oral cavity for dental erosion (Clin Oral Investig 2008 Mar;12 Suppl 1:S5 full-text)
Abdomen:
 splenomegaly in portal hypertension
Diagnosis
Making the diagnosis:
 risky or hazardous alcohol use - drinking more than recommended daily, weekly, or per-occasion
amount resulting in increased risk for health consequences(3)
o for men, > 14 drinks per week or > 4 drinks per occasion
o for women, > 7 drinks per week or > 3 drinks per occasion
 Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria
o alcohol abuse
 maladaptive pattern of alcohol use leading to significant impairment or distress
 not meeting criteria for alcohol dependence
 one or more of the following within 12 months
 recurrent drinking resulting in failure to fulfill major role obligations
  recurrent drinking in situations in which it is physically hazardous
 recurrent alcohol-related legal problems
 continued alcohol use despite persistent or recurrent social or interpersonal problems
caused or exacerbated by alcohol
o alcohol dependence
 maladaptive pattern of alcohol use leading to significant impairment or distress
 3 or more of the following within 12 months
 need for significantly increased amounts of alcohol to achieve intoxication or desired
effect, or significantly diminished effect with continued use of the same amount of
alcohol
 alcohol withdrawal syndrome, or use of substances to relieve or avoid withdrawal
symptoms
 persistent desire or unsuccessful efforts to cut down or control drinking
 drinking more or longer than intended
 giving up or reducing activities due to drinking
 considerable time spent in activities to obtain alcohol, drink, or recover from alcohol
effects
 continued drinking despite knowledge of having persistent or recurrent physical or
psychological problems exacerbated by alcohol use
 considered physical dependence (in addition to psychological dependence) if evidence of
tolerance or withdrawal
o Reference - Addiction 2006 Sep;101 Suppl 1:59 EBSCOhost Full Text
Differential diagnosis:
 other substance use disorders
 depression
 anxiety
Testing overview:
 no testing needed to make diagnosis
 if suspecting liver disease(1)
o blood tests
 complete blood count with platelets
 prothrombin time (PT)/international normalized ratio (INR)
 partial thromboplastin time (PTT)
 liver function tests
 aspartate aminotransferase (AST)
 alanine aminotransferase (ALT)
 gamma-glutamyltransferase (GGT)(2)
o imaging studies
 abdominal ultrasound
 computed tomography
Blood tests:
 liver tests
o elevated aspartate aminotransferase (AST) level < 300 units/mL(1)
o aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio > 2(1)
o gamma-glutamyltransferase (GGT)/alkaline phosphatase ratio > 2.5 suggests alcohol-induced liver
damage(2)
o international normalized ratio (INR) may be elevated(1)
 complete blood count with peripheral smear
o anemia (Alcohol Health Res World 1997;21(1):42 EBSCOhost Full Text)
o thrombocytopenia (Alcohol Health Res World 1997;21(1):42 EBSCOhost Full Text)
o macrocytosis - elevated mean corpuscular volume (MCV)
 elevated MCV has low sensitivity and high specificity for alcohol abuse (Ann Intern Med 1984
Dec;101(6):847, Alcohol Clin Exp Res 1984 May-Jun;8(3):253)
 macrocytosis may persist in some alcoholics even after prolonged abstinence, based on study
of 54 patients (JAMA 2001 Dec 19;286(23):2946)
  carbohydrate-deficient transferrin (CDT) does not appear useful as screening test for
detecting heavy drinking in primary care settings (level 2 [mid-level] evidence)
o based on cohort study
o 799 patients aged 30-60 years were interviewed for drinking history and had blood test for CDT
o 18 patients (2.25%) met criteria for heavy drinking (≥ 90 drinks in prior 30 days or ≥ 42 g of
alcohol per day)
o using CDT > 2.5% as cut-off value
 sensitivity 61%
 specificity 85%
 positive predictive value 9%
 negative predictive value 98.95%
o Reference - J Am Board Fam Pract 2004 Jul-Aug;17(4):247 full-text
o DynaMed commentary -- negative predictive value of 98.95% not clearly useful because pretest
probability of not having heavy drinking was 97.75%
Treatment
Treatment overview:
 brief interventions
o brief interventions may reduce mortality in heavy drinkers (level 2 [mid-level] evidence)
o brief primary care physician intervention can decrease alcohol use, problem drinking and
hospitalization in problem drinkers (level 1 [likely reliable] evidence)
o brief interventions in primary care settings may reduce alcohol consumption in hazardous drinkers,
including patients not specifically seeking alcohol-related treatment (level 2 [mid-level] evidence)
 longer-term psychologic interventions with evidence for efficacy include
o cognitive behavioral therapy (level 2 [mid-level] evidence)
o network support (to help patient change social network) (level 2 [mid-level] evidence)
o behavioral couple therapy (for females with alcohol use disorder) (level 2 [mid-level] evidence)
 integrated medical and substance abuse treatment appears to improve abstinence rates at 6 months in
patients with substance-abuse related medical conditions (level 2 [mid-level] evidence)
 pharmacologic therapy may have adjunctive role
o disulfiram (Antabuse) produces unpleasant symptoms with small amounts of alcohol
 500 mg orally once daily, may reduce dose if sedation
 may reduce days of drinking but not improve total abstinence (level 2 [mid-level] evidence)
o naltrexone (Depade, ReVia, generic) is opiate antagonist
 50 mg orally once daily; alternative is naltrexone 380 mg (Vivitrol) intramuscularly every 4
weeks
 naltrexone appears to reduce heavy drinking and relapse rate (level 2 [mid-level] evidence)
o acamprosate (Campral) has different mechanism of action
 666 mg orally 3 times daily with meals
 acamprosate may reduce risk of drinking after completion of detoxification in alcohol
dependent patients (level 2 [mid-level] evidence)
o acamprosate and naltrexone may similarly reduce risk for drinking after detoxification in alcohol
dependent patients (level 2 [mid-level] evidence), evidence for combination therapy limited and
conflicting
o sertraline plus naltrexone may increase abstinence rate and decrease depression symptoms
compared to either sertraline or naltrexone alone for patients with depression and alcohol
dependence (level 2 [mid-level] evidence)
o anticonvulsants may reduce alcohol consumption in adults with alcohol dependence (level 2 [mid-
level] evidence)
 topiramate (Topamax) (off-label use of antiepileptic drug)
 25 mg orally once daily titrated to 150 mg orally twice daily
 topiramate may reduce heavy drinking and may improve quality of life but often not
tolerated (level 2 [mid-level] evidence)
 gabapentin associated with increased abstinence and reduced heavy drinking in adults with
alcohol dependence (level 2 [mid-level] evidence)
o baclofen (Lioresal) may be effective for maintaining alcohol abstinence in patients with alcoholic
cirrhosis, and may reduce alcohol craving and intake (level 2 [mid-level] evidence)
 o ondansetron (Zofran) may be effective in reducing drinking in early-onset alcoholics (level 2 [mid-
level] evidence)
 insufficient evidence from randomized trials regarding effectiveness of 12-step programs, but
observational evidence suggests Alcoholics Anonymous (AA) attendance may reduce alcohol
consumption and depressive symptoms (level 2 [mid-level] evidence)
 combination of smoking cessation intervention plus alcohol intervention may decrease alcohol
consumption and increase long-term abstinence rates (level 2 [mid-level] evidence)
Diet:
 advise nutritional intake to achieve Dietary Reference Intakes (N Engl J Med 2009 Jun
25;360(26):2758)
Counseling:
 behavioral counseling may reduce alcohol consumption in patients with alcohol use
disorder (level 2 [mid-level] evidence)
o based on systematic review limited by clinical heterogeneity
o systematic review of 23 randomized trials (with duration ≥ 6 months) evaluating behavioral
counseling for adolescents and adults with alcohol use disorder
o behavioral counseling interventions varied across studies and included
 brief advice, feedback, or motivational interviews
 cognitive behavioral strategies, such as self-completed action plans, written health education
or self-help materials
 drinking diaries
 problem-solving exercises
o control interventions included usual care, educational materials, and advice from nurse
o compared to control interventions at 12 months, behavioral counseling associated with
 reduced alcohol consumption
 in adults (mean difference 3.6 drinks/week, 95% CI 2.4-4.8 drinks/week) in analysis of
10 trials with 4,332 patients
 in young adults/college students (mean difference 1.7 drinks/week, 95% CI 0.7-2.6
drinks/week) in analysis of 3 trials with 1,421 patients
 reduced heavy drinking episodes (risk difference 12%, 95% CI 7%-16%) in analysis of 7
trials with 2,727 adult patients
 increased number of patients achieving recommended drinking limit (risk difference 11%,
95% CI 8%-13%) in analysis of 9 trials with 5,973 adult patients
o insufficient evidence to draw conclusions about effect of behavioral counseling on accidents,
injuries, or alcohol-related liver problems in adults
o Reference - Ann Intern Med 2012 Nov 6;157(9):645
 motivational interviewing and cognitive behavioral therapy may reduce alcohol misuse in
patients with comorbid depression or anxiety disorders (level 2 [mid-level] evidence)
o based on systematic review limited by clinical heterogeneity
o systematic review of 8 randomized trials comparing different psychological interventions for
alcohol misuse in patients with comorbid depression or anxiety disorders
o meta-analysis precluded by heterogeneity in patient characteristics and treatment regimens
o motivational interviewing and cognitive behavioral interventions associated with significant
reductions in alcohol consumption and depressive and/or anxiety symptoms
o longer interventions generally more effective than brief interventions
o Reference - J Affect Disord 2012 Aug;139(3):217
 psychosocial interventions for decreasing alcohol consumption in adults with problematic
drug and alcohol use have limited evidence to evaluate efficacy and adverse effects
o based on Cochrane review
o systematic review of 4 randomized trials evaluating psychosocial interventions for reducing alcohol
consumption in 594 adults with problematic drug and alcohol use
o meta-analysis precluded by heterogeneity in comparisons and outcome measures
o brief motivational intervention decreased alcohol consumption vs. assessment only in 1 trial with
187 adults
o no significant difference in alcohol consumption comparing
 brief intervention on alcohol use vs. treatment as usual in 1 trial with 110 adults
 cognitive-behavioral coping skills training vs. 12-step facilitation in 1 trial with 41 adults
  hepatitis health promotion vs. individual or group motivational interviewing in 2 trials with
324 adults
o Reference - Cochrane Database Syst Rev 2014 Dec 3;(12):CD009269
 early interventions may reduce frequency and quantity of alcohol use in adolescents (level
2 [mid-level] evidence)
o based on systematic review without assessment of allocation concealment
o systematic review of 9 randomized and quasi-randomized trials comparing early interventions to
usual care for substance use in 1,895 adolescents aged 13-19 years using alcohol or other drugs
but not meeting criteria for abuse or dependence
 interventions included motivational interviewing, life skills training, antiviolence models, and
value clarification procedures
 5 trials evaluated frequency or quantity of alcohol use
o early interventions associated with reduced
 frequency of alcohol use in analysis of 5 trials (p = 0.008), results limited by significant
heterogeneity
 quantity of alcohol use in analysis of 4 trials (p = 0.0004)
 episodes of binge drinking in analysis of 4 trials (p = 0.001)
o Reference - Subst Abuse Treat Prev Policy 2012 Jun 14;7(1):25 PDF
Brief interventions:
 United States Preventive Services Task Force (USPSTF) recommends screening adults ≥ 18 years old
for alcohol misuse and providing persons engaging in risky or hazardous drinking with brief behavioral
counseling to reduce alcohol misuse (USPSTF Grade B)(3)
 brief interventions may include
o motivational interviews of varying length and number
o cognitive behavioral therapy
o self-completed action plans
o written health-education or self-help materials
o requests to keep drinking diaries
o written personalized feedback
o follow-up telephone counseling
o exercises to complete at home
 brief interventions may reduce mortality in heavy drinkers (level 2 [mid-level] evidence)
o based on systematic review with clinical heterogeneity
o systematic review of 4 randomized trials with 1,540 heavy drinkers
o follow-up time frames varied from 1-10 years
o 3 of 4 trials excluded heavy drinkers who were alcohol dependent
o one study was limited to only patients ≥ 65 years old
o brief interventions varied in duration, frequency, and manner of delivery
o pooled relative risk of death for brief intervention 0.47 (95% CI 0.25-0.89)
o Reference - Addiction 2003 Jul;99(7):839 EBSCOhost Full Text
 personalized feedback interventions delivered in person or by computer may have similar
efficacy for decreasing short-term alcohol use and alcohol-related problems in
adolescents and young adults (level 2 [mid-level] evidence)
o based on systematic review without assessment of trial quality
o systematic review of 13 randomized trials comparing in-person vs. computer-delivered
personalized feedback interventions for alcohol misuse in 2,441 adolescents and young adults
 mean participant age ranged from 16.8 to 20.6 years across trials, 9 trials conducted in
college students
 follow-up ranged from 1 to 15 months, short-term follow-up defined as ≤ 4 months
o comparing in-person to computer-delivered personalized feedback interventions
 no significant differences in any alcohol use variables or alcohol related problems at short-
term follow-up
 in-person personalized feedback interventions associated with significantly reduced drinks
per week and alcohol quantity at > 4 months in analyses of 5 trials with 635 participants
o no other differences between groups at > 4 months
o Reference - J Consult Clin Psychol 2015 Apr;83(2):430 full-text
Brief interventions in primary care:
 brief primary care physician intervention can decrease alcohol use, problem drinking and
hospitalization in problem drinkers (level 1 [likely reliable] evidence)
o based on randomized trial
o 774 problem drinkers aged 18-65 years (482 men and 292 women) randomized to receive either
workbook-based intervention during two 15-minute physician visits 1 month apart (and contract
to reduce alcohol intake) vs. booklet on general health
 problem drinkers defined as men who consumed > 14 drinks (168 g)/week and women who
had > 11 drinks (132 g)/week, or > 5 drinks at least 4 times in past month
 intervention consisted of 2 physician visits and 2 nurse follow-up phone calls covering review
of normative drinking, patient-specific alcohol effects, worksheet on drinking cues, drinking
diary cards, and drinking agreement in prescription format
 adults in 17 private community-based primary care practices in Wisconsin completed health
screening survey
 a drink in this study contains 12 g of alcohol
o comparing workbook-based intervention vs. control at 12 months
 women decreased alcohol consumption by 47% vs. 16% (p < 0.001, NNT 4)
 men decreased alcohol consumption by 37% vs. 23% (p < 0.001, NNT 8)
 total days of hospitalization in men 178 vs. 314 (p < 0.01)
 no differences in days of hospitalization in women
 intervention significantly reduced 7-day alcohol use, number of binge drinking episodes,
frequency of excessive drinking; trend toward fewer emergency department visits,
nonsignificant reduction in mortality
o Reference - Project TrEAT - Trial for Early Alcohol Treatment (JAMA 1997 Apr 2;277(13):1039)
o at 4-year follow-up, no significant differences between treatment and control groups in overall
drinking rates, in rates of heavy drinking in men, or in binge drinking rates in women
o significant differences seen between treatment and control groups in female heavy drinkers
(consuming > 13 drinks in previous 7 days) and male binge drinkers (consuming > 5 drinks on
one occasion in previous 30 days)
o Reference - Alcohol Clin Exp Res 2002 Jan;26(1):36
o brief interventions may reduce problem drinking in women of childbearing age (level
2 [mid-level] evidence)
 based on subgroup analysis of randomized trial
 205 women randomized to intervention (two 15-minute physician visits with advice,
education and contracting using scripted workbook) vs. control
 174 (85%) completed 48 months of follow-up
 intervention significantly reduced 7-day alcohol use (p = 0.0039) and binge drinking
episodes (p = 0.0021) throughout 48 months
 Reference - Project TrEAT (Alcohol Clin Exp Res 2000 Oct;24(10):1517)
o net benefit seen when costs analyzed from societal perspective (ACP J Club 2002 Sep-
Oct;137(2):58)
o subgroup analysis of 226 young adults ≤ 30 shows significant difference in heavy drinking rates
between groups sustained at 36 months (Ann Fam Med 2004 Sep-Oct;2(5):474 EBSCOhost
Full Text full-text)
 multifaceted intervention may reduce at-risk drinking at 3 months but not at 12 months
in older adults (level 2 [mid-level] evidence)
o based on randomized trial with high loss to follow-up
o 631 adults ≥ 55 years old considered at-risk drinkers by Comorbidity Alcohol Risk Evaluation Tool
(CARET) were randomized to multifaceted intervention in primary care vs. control
 intervention included personalized report on alcohol associated risk behaviors, educational
booklet on alcohol and aging, drinking diary, discussion with written advice from primary
care provider, and motivational interviewing telephone counseling from health educator to
reduce alcohol consumption at 2, 4, and 8 weeks
 control included booklet outlining recommended behaviors for alcohol use, nutrition,
exercise, medication use, smoking, and encouragement to discuss with primary care
physician
o 21% lost to follow-up at 12 months
o comparing intervention vs. control at 3 months
  proportion of patients considered at-risk drinker 49.6% vs. 61.2% (adjusted odds ratio [OR]
0.41, 95% CI 0.22-0.75)
 ≥ 1 heavy drinking days in previous 7 days in 10.3% vs. 16.9% (adjusted OR 0.46, 95% CI
0.22-0.99)
o no significant differences for either outcome at 12 months
o Reference - Addiction 2011 Jan;106(1):111 EBSCOhost Full Text full-text
 physician advice can decrease excessive alcohol use by older adults (level 1 [likely
reliable] evidence)
o based on randomized trial
o 158 patients > 65 years old randomized to intervention (general health booklet and two 10-15
minute physician-delivered counseling sessions 1 month apart including advice, education and
contracting using scripted workbook) vs. control (general health booklet) and followed every 3
months for 1 year
o nurse contacted patient by phone 2 weeks after each visit
o inclusion criteria
 men consuming > 11 drinks/week or binge drinking (> 4 drinks per occasion 2 or more
times in past 3 months)
 women consuming > 8 drinks/week or binge drinking (> 3 drinks per occasion 2 or more
times in past 3 months)
 2 or more positive responses to CAGE questionnaire
o patients excluded if attended alcohol treatment program or had symptoms of alcohol withdrawal
in previous year, had physician advice to change alcohol use in previous 3 months, drank > 50
drinks/week or had suicidal ideation
o comparing intervention to control at 12 months
 mean number of drinks in previous 7 days 9.9 vs. 16.3 (p < 0.001)
 binge drinking in previous 30 days in 30.8% vs. 49.3% (p < 0.005, NNT 6)
 excessive alcohol use in prior 7 days in 15.4% vs. 34.3% (p < 0.005, NNT 6)
o no significant changes in health status
o Reference - Project GOAL (J Fam Pract 1999 May;48(5):378), commentary can be found in
Evidence-Based Medicine 1999 Nov-Dec;4(6):172
 brief physician intervention may reduce binge drinking (level 2 [mid-level] evidence)
o based on randomized trial without attention control
o 752 binge drinkers randomized to brief physician counseling intervention vs. usual care and
followed for 12 months
o physician intervention was 2 face-to-face counseling sessions (10 to 15 minutes each) during
routine patient care plus nurse contact at 2 weeks and 8 weeks to reinforce
o comparing physician intervention vs. control at 12 months
 binge drinking episodes during previous 30 days in 52.3% vs. 67.2% (p < 0.001, NNT 7)
 mean number of binge drinking episodes during previous 30 days 1.14 vs. 1.56 (p < 0.001)
 mean number of drinks in previous 7 days 19.2 vs. 22.24 (p < 0.001)
o Reference - Am J Med 2010 Jan;123(1):72
 brief interventions in primary care settings may reduce alcohol consumption in hazardous
drinkers, including patients not specifically seeking alcohol-related treatment (level 2
[mid-level] evidence)
o based on 3 systematic reviews with methodologic limitations
o Cochrane review with substantial heterogeneity
 systematic review of 29 randomized trials comparing brief interventions (not exceeding 4
sessions) for reducing alcohol consumption vs. control treatment delivered in general
practice or emergency departments with participants not seeking alcohol treatment
 control treatments included assessment only, standard treatment, nonintervention or
extended psychological intervention
 brief intervention reduced consumption compared to control after ≥ 1-year follow-up (mean
difference -38 grams/week, 95% CI -54 to -23 grams/week) in meta-analysis of 22 trials
with 7,619 patients (mean age 43 years), results limited by significant heterogeneity
 in subgroup analysis of 8 trials with 2,307 participants at 1-year follow-up
 benefit found in men (mean difference -57 grams/week, 95% CI -89 to -25
grams/week)
  benefit not found in women (mean difference -10 grams/week, 95% CI -48 to 29
grams/week)
 nonsignificant trends for greater efficacy with more intervention
 increased reduction in consumption of 1 gram/week (95% CI -0.1 to 2.2 grams/week, p
= 0.09) for each extra minute of treatment exposure
 extended intervention associated with greater reduction in consumption compared to
brief intervention (mean difference -28 grams/week, 95% CI -62 to 6 grams/week)
 Reference - Cochrane Database Syst Rev 2008 Oct 8;(4):CD004148, Cochrane for Clinicians
summary can be found in Am Fam Physician 2009 Mar 1;79(5):370, commentary on earlier
version can be found in Evid Based Med 2007 Dec;12(6):179
o systematic review of 56 randomized trials without evidence of quality assessment
 brief interventions defined as interventions with ≤ 4 sessions
 34 trials involved patients not seeking treatment
 27 (79%) trials excluded any patients who
 drank at high levels or for long period of time
 had alcohol dependence
 had previous treatment for alcohol problems
 brief interventions (compared to no intervention) significantly reduced drinking at 3-12
months, modest benefit after 12 months did not reach statistical significance and results at
> 3-6 months follow-up significant only if trials with heavy drinkers excluded
 20 trials involved patients seeking treatment and compared brief interventions to patients
receiving extended treatment
 brief intervention no less effective than extended treatment in 20 trials of patients
seeking treatment, but trend for reduced drinking at 3-6 months with extended
treatment
 authors question definition of brief interventions in some studies, indicating brief
interventions in treatment seeking individuals may not meet generally accepted ideas of
brief intervention
 Reference - Addiction 2002 Mar;97(3):279 EBSCOhost Full Text in ACP J Club 2002
Sep-Oct;137(2):58
o systematic review of 19 randomized trials of "brief intervention" or "motivational intervention"
with 5,639 outpatients actively attending primary care and not seeking alcohol treatment
 intention-to-treat analysis used with no change assumed for patients with missing data
 15 trials used customary alcohol intake as inclusion criteria, 14 trials excluded alcohol-
dependent patients
 9 trials had follow-up rates > 80% (mean 72%, range 32% to 92%)
 trial quality ranged from 5 to 14 on 18-point scale (mean 9.6)
 high-quality trials (score 10 or higher) were more likely to report statistically significant
positive effects than low-quality trials
 meta-analysis of 12 trials for outcome of change in alcohol consumption found brief alcohol
intervention associated with reduction in alcohol use at 6 or 12 months by 38 g/week (95%
CI 24-51 g/week), or about 3 drinks per week, Project TrEAT accounted for about 40% of
this analysis
 healthcare utilization reported in 3 trials, inconsistent results suggesting benefit or no effect
 mortality reported in 1 trial with significant reduction at 3 years but not 4 years
 Reference - Arch Intern Med 2005 May 9;165(9):986 full-text, commentary can be found
in Am Fam Physician 2006 Jan 1;73(1):150
o similar results can be found in systematic review of 6 meta-analyses and 1 systematic review
(Prev Med 2014 Dec 13 early online)
 motivational interviewing may only slightly reduce quantity and frequency of alcohol
consumption in young adults (level 2 [mid-level] evidence)
o based on Cochrane review of trials with methodologic limitations
o systematic review of 66 randomized trials evaluating motivational interviewing for prevention of
alcohol misuse in 17,901 patients ≤ 25 years old
o all trials had ≥ 1 limitation including
 unclear or no allocation concealment
 lack of blinding
 o features of motivational interviewing included awareness, common beliefs about drinking alcohol,
and problem-solving or decision-making skills (or both)
o comparing motivational interviewing to assessment only or alternative intervention (control) at ≥
4 months, motivational interviewing associated with
 decreased alcohol consumption (equivalent to 1.5 fewer drinks per week vs. control) in
analysis of 28 trials with 6,676 patients
 lower frequency of alcohol consumption (equivalent to 0.17 day reduction in drinking days
per week vs. control) in analysis of 16 trials with 4,390 patients, results limited by significant
heterogeneity
 fewer alcohol problems (equivalent to 0.7 point reduction on 69 point scale) in analysis of 24
trials with 6,742 patients, results limited by significant heterogeneity
 nonsignificant decrease in binge drinking in analysis of 16 trials with 4,028 patients
o Reference - Cochrane Database Syst Rev 2014 Aug 21;(8):CD007025
 trials of screening plus brief intervention for patients who screen positive have inconsistent results
o screening for high-risk drinking and 5-10 minutes of advice and counseling during
primary care visit may reduce high-risk alcohol consumption (level 2 [mid-level]
evidence)
 based on trial with cluster randomization and large loss to follow-up
 3 primary care internal medicine practice sites randomized to intervention site vs. control
with additional control site added 22 months into the trial
 9,772 patients aged 21-70 years attending these practices screened for high-risk drinking,
defined as any of
 men consuming > 12 standard drinks per week (standard drink = 12.8 g of alcohol such
as 5 ounces of wine, 12 ounces of beer, or 1.5 ounces of 80-proof liquor)
 women consuming > 9 standard drinks per week
 binge drinking (5 or more drinks for men, 4 or more drinks for women) in previous
month
 intervention site providers were asked to provide 5-10 minutes of patient-centered alcohol
counseling at next regular patient visit for patients who screened positive for high-risk
drinking
 1,760 patients screened positive of whom 530 came for another regular patient visit and
were included in the study, 447 completed 12-month interview
 gender-adjusted outcomes from baseline to 12 months
 comparing patients at intervention sites vs. control sites
 mean number of drinks per week decreased from 18.3 to 12.6 vs. 16.3 to 13.3
 binge drinking episodes per month decreased from 4.8 to 2.6 vs. 3.8 to 2.4
 Reference - J Gen Intern Med 2005 Jan;20(1):7 full-text, summary can be found in Am Fam
Physician 2005 Nov 1;72(9):1867
o addition of lifestyle counselling and/or brief advice to patient information leaflet may
not reduce hazardous alcohol consumption compared to patient information leaflet
alone in adults with alcohol use disorder (level 2 [mid-level] evidence)
 based on cluster-randomized trial with low compliance
 756 adults (mean age 45 years) who screened positive for alcohol use disorder randomized
by primary care practice to 1 of 3 interventions
 structured brief advice for 5 minutes plus patient information leaflet
 brief lifestyle counselling for 20 minutes plus structured brief advice for 5 minutes plus
patient information leaflet
 patient information leaflet alone
 all patients were not seeking alcohol-related treatment at baseline
 provision of patient leaflet and brief advice occurred directly after screening but brief
lifestyle counselling was provided in subsequent consultation
 57% in brief lifestyle counselling group attended session but 99%-100% in other groups
received allocated intervention
 no significant difference in negative alcohol use disorders identification test at 6 or 12
months comparing either structured brief advice or brief lifestyle counselling to leaflet alone
in intention-to-treat analyses
 Reference - SIPS trial (BMJ 2013 Jan 9;346:e8501 full-text)
 o screening and brief intervention in general practice may be ineffective (level 2 [mid-
level] evidence)
 based on pragmatic controlled trial with low follow-up rate
 39 general practitioners randomized to give brief counseling intervention vs. no intervention
to patients
 906 risky drinkers identified out of 6,897 adults screened
 537 (59%) had research follow-up at 12-14 months
 of 442 patients exposed to brief counseling session, only 79 (17.9%) attended follow-up
consultation offered by general practitioner
 average weekly consumption increased by 0.7 drinks in both groups at 1-year follow-up
 Reference - Alcohol Alcohol 2007 Nov-Dec;42(6):593 full-text
 screening for excessive alcohol use and providing brief intervention "created
more problems than it solved"
 based on qualitative study of 24 generalist physicians who participated in pragmatic
study of screening and brief intervention for excessive alcohol use
 Reference - BMJ 2002 Oct 19;325(7369):870 full-text, commentary can be found in BMJ
2003 Feb 8;326(7384):336, BMJ 2003 Mar 8;326(7388):550
o addition of brief intervention to usual care may not reduce alcohol consumption in
patients with opiate or cocaine dependence and problematic alcohol use (level 2
[mid-level] evidence)
 based on randomized trial with unclear blinding
 112 adult outpatients with opiate or cocaine dependence and problematic alcohol use
randomized to brief intervention plus treatment as usual vs. treatment as usual alone and
followed for 9 months
 brief intervention provided by multidisciplinary team of healthcare professionals to promote
self-observation in consumption of alcohol
 both treatments reduced alcohol consumption from baseline at 3 months (p < 0.05) but not
at 9 months
 no significant differences between treatments in alcohol consumption at any time point
 Reference - Subst Abuse Treat Prev Policy 2011 Aug 17;6:22 full-text
Brief interventions in hospital settings:
 brief interventions in hospital settings for heavy alcohol users might reduce alcohol
consumption and mortality (level 2 [mid-level] evidence)
o based on Cochrane review with heterogeneity and trials with methodologic limitations
o systematic review of 14 randomized or controlled trials comparing brief interventions to reduce
alcohol consumption vs. usual care in 4,041 heavy alcohol users admitted to hospital inpatient
units for treatments not related to alcohol use
o intervention consisted of 1-3 sessions of counseling focused on reducing alcohol consumption
o all but 1 trial had methodologic limitations and this trial did not have full intention-to-treat
analysis
o brief intervention generally associated with reduction in mean alcohol consumption during
subsequent follow-up
 at 4 months no significant difference in 1 trial with 616 patients (511 patients analyzed)
 at 6 months, statistically significant reduction in analysis of 4 trials with 453 patients
analyzed, analysis limited by heterogeneity
 at 9 months, statistically significant reduction in 1 trial with 616 patients (511 patients
analyzed)
 at 1 year, nonsignificant reduction in analysis of 4 trials with 1,073 patients analyzed
o limited data reported for measures of heavy drinking
 significant reduction in heavy drinking episodes in 1 trial with 616 patients (511 patients
analyzed)
 no difference in number of binges in 1 trial with 287 patients
o brief intervention might be associated with lower mortality during subsequent follow-up
 at 3 months no significant difference in 1 trial with 29 patients analyzed
 at 4 months no significant difference in 1 trial with 616 patients (520 patients analyzed)
 at 6 months, statistically significant reduction in analysis of 4 trials with 1,166 patients
analyzed
  risk ratio (RR) 0.42 (95% CI 0.19-0.94)
 NNT 39-528 with 3% mortality in controls
 analysis limited by heterogeneity
 at 9 months no significant difference in 1 trial with 616 patients (495 patients analyzed)
 at 1 year, statistically significant reduction in analysis of 7 trials with 2,396 patients analyzed
 RR 0.6 (95% CI 0.4-0.91)
 NNT 37-246 assuming 5% mortality in controls
 only 1 of the 7 trials was statistically significant individually
o Reference - Cochrane Database Syst Rev 2011 Aug 10;(8):CD005191
 brief motivational intervention associated with reduced alcohol consumption in injured
patients with alcohol dependence (level 2 [mid-level] evidence)
o based on randomized trial with high dropout rate
o 1,336 patients (82% male) in trauma care setting assessed for alcohol dependence randomized
to brief motivational interview vs. treatment as usual (informational handouts provided)
o follow-up assessment completed by
 77% at 6 months
 66% at 12 months
o brief motivational intervention associated with decreased alcohol consumption (compared to
baseline) at
 6 months (p = 0.03)
 12 months (p = 0.02)
o Reference - Drug Alcohol Depend 2010 Sep 1;111(1-2):13
 brief intervention no more effective than scripted discharge instructions for patients with
hazardous/harmful drinking in emergency department (level 1 [likely reliable] evidence)
o based on randomized trial
o 494 persons ≥ 18 years old reporting hazardous/harmful drinking (mean 13.6 drinks per week)
in emergency department randomized to brief (5-10 minute) motivational intervention by
physician (Brief Negotiation Interview) vs. scripted discharge instructions
o 92% completed evaluations at 6 months and 12 months
o no significant differences comparing intervention vs. discharge instructions at 12 months
 mean drinks per week 9.8 vs. 9.8
 binge drinking episodes per month 4 vs. 3.9
o Reference - Ann Emerg Med 2008 Jun;51(6):742, editorial can be found in Ann Emerg Med 2008
Jun;51(6):751
 brief intervention in emergency department may reduce alcohol consumption and driving
after drinking in patients with hazardous/harmful drinking (level 2 [mid-level] evidence)
o based on randomized trial with low adherence
o 889 adults in emergency department with hazardous and harmful drinking randomized to 1 of 4
groups and followed for 12 months
 brief motivational intervention by emergency practitioner (Brief Negotiation Interview)
 Brief Negotiation Interview with 1-month follow-up telephone booster
 standard care with assessments
 standard care with no assessments
o 59% completed interactive voice response assessment at 12 months
Brief Brief Negotiation
Overall at Negotiation Interview with Standard p for
Baseline Interview Telephone Booster Care Trend
p=
Mean drinks per week 19.8-20.9 14.3 13 17.6 0.045

Mean binge drinking

days during past 28 days 7.2-7.5 5.1 4.7 5.8 p = 0.03

Driving after drinking > 3

drinks > 1 time during
past 12 months 38%-43% 29% 31% 42% p = 0.04
Outcomes at 12 Months:
o no significant differences in reduction in drinks per week or in binge drinking days comparing
  Brief Negotiation Interview with vs. without telephone booster
 standard care with vs. without assessment
o no significant differences between treatments in arrests for driving under influence, motor
vehicle crash while intoxicated, contact with legal system, or missing ≥ 1 workday
o Reference - Ann Emerg Med 2012 Aug;60(2):181
 therapist-delivered brief intervention in emergency department for adolescents with
prior alcohol misuse and aggression may reduce alcohol consequences for 6 months and
violence consequences for 1 year (level 2 [mid-level] evidence)
o based on randomized trial without attention control
o 726 patients aged 14-18 years presenting to emergency department (ED) for medical illness or
injury and who self-reported past-year alcohol misuse and aggression randomized to 1 of 3
treatments delivered in ED
 computerized brief intervention for alcohol and violence
 therapist-delivered brief intervention for alcohol and violence
 brochure for alcohol and violence (control)
o all patients completed computerized self-assessment prior to randomization
o alcohol consequences included missed school, trouble getting along with friends because of
drinking, etc.
o patients dropped out of school at baseline (p = 0.02)
 14.4% for computerized intervention
 7.5% for therapist-delivered intervention
 8.5% for control
o therapist-delivered intervention associated with significant reductions in (vs. control)
 peer aggression at 3 months
 experience of peer violence at 3 months
 violence consequences at 3 months
 alcohol consequences at 6 months
o computerized intervention associated with significant reduction in alcohol consequences at 6
months vs. control
o Reference - SafERteens trial (JAMA 2010 Aug 4;304(5):527 full-text), editorial can be found
in JAMA 2010 Aug 4;304(5):575
o DynaMed commentary -- trial was not powered to compare active interventions against each
other
o therapist-delivered brief intervention in ED associated with decrease in violence but
not alcohol misuse at 1-year follow-up
 based on 1-year follow-up of SafERteens trial
 84% from original trial included in follow-up
 therapist-delivered intervention associated with decrease in
 peer aggression (p < 0.01 vs. control)
 peer victimization (p < 0.05 vs. control)
 no significant differences in alcohol misuse
 Reference - Pediatrics 2012 Jun;129(6):1083 full-text
 brief telephone intervention after emergency room visit may reduce risky behavior in
patients with alcohol use disorder (level 2 [mid-level] evidence)
o based on randomized trial without attention control
o 285 motor vehicle crash patients (mean age 29 years) randomized to brief telephone
intervention vs. standard care after emergency room discharge and followed for 3 months
o telephone intervention consisted of 2 brief telephone sessions discussing risky alcohol use
o reduction in self-reported impaired driving was significantly greater in telephone intervention
group vs. control group at (p = 0.04)
o no difference between groups in self-reported risky alcohol use
o Reference - Ann Emerg Med 2008 Jun;51(6):755
 brief motivational intervention during hospitalization with telephone booster session
may reduce alcohol consumption up to 6 months but reduction less compelling by 1 year
in patients with trauma (level 2 [mid-level] evidence)
o based on randomized trial with high dropout rate
 o 596 injured patients in trauma center (57% meeting criteria for moderate-to-severe problem
drinking) were randomized to 1 of 3 clinician-delivered interventions and followed for 1 year
 brief motivational intervention (mean duration 23 minutes) during hospitalization
 brief motivational intervention plus telephone booster session with personalized feedback at
30 days
 brief advice for 5 minutes during hospitalization
o all patients blood alcohol concentration > 0.01 at admission, self-reported drinking within 6
hours of injury, or score ≥ 3 in women or ≥ 4 in men on Alcohol Use Disorders Identification
Test
o 25% did not complete 12-month assessment, but all patients were included in analyses
o compared to brief advice and brief motivational intervention, brief motivational intervention plus
booster associated with reductions in
 number of drinks per week at
 3 months (adjusted mean difference 1.22, p = 0.01)
 6 months (adjusted mean difference 1.42, p = 0.02)
 percent days of heavy drinking at 6 months (adjusted mean difference 5.9, p = 0.04)
 maximum number of drinks per 1 day at
 3 months (adjusted mean difference 1.38, p = 0.003)
 12 months (adjusted mean difference 1.71, p = 0.02)
 number of drinks per drinking day
 3 months (adjusted mean difference 1.49, p = 0.002)
 6 months (adjusted mean difference 1.28, p = 0.01)
o compared to brief advice at 1 year
 brief motivational intervention associated with reduction in days of heavy drinking
(difference about 8%, p < 0.05)
 brief motivational intervention plus booster associated with reduction in maximum number
of drinks per day (mean difference about 2 drinks, p < 0.05)
o no significant differences among groups in mean number of drinks per drinking day OR mean
number of drinks per week at 1 year
o Reference - Ann Surg 2014 May;259(5):873
 peer intervention in pediatric emergency department may increase quit attempts but
does not appear to reduce alcohol consumption at 3 and 12 months (level 2 [mid-level]
evidence)
o based on randomized trial with high dropout rate
o 853 patients aged 14-21 years in pediatric emergency department who screened positive on
Alcohol Use Disorders Identification Test (AUDIT) randomized to 1 of 3 groups and followed for
12 months
 intervention received peer-conducted motivational intervention, referral to community
resources with or without treatment, and telephone support at day 10 plus standard
assessment
 minimally-assessed control received resource written advice on alcohol-related risks, and 12-
month follow-up appointment
 standard-assessed control received minimally-assessed control protocol plus standardized
assessment
o 72% had follow-up at 12 months
o comparing intervention vs. standard-assessed control at 12 months
 attempt to quit drinking in 40.5% vs. 27.8% (p = 0.007, NNT 8)
 attempt to be careful when drinking in 80.5% vs. 71.3% (p = 0.03, NNT 11)
 attempt to cut back on drinking 73.3% vs. 64.9% (not significant)
o similar results at 3 months
o no significant differences among groups in consumption, alcohol-related consequences and
alcohol-related risk behaviors at 12 months
o Reference - Acad Emerg Med 2010 Aug;17(8):890 full-text
 peer intervention for hospitalized patients with alcohol problems associated with
increased abstinence at 6 months (level 2 [mid-level] evidence)
o based on nonrandomized trial with high dropout rate
o 314 patients hospitalized with alcohol-related injuries randomized to 1 of 3 treatments
 peer intervention (physician message plus 30-60 minute visit with a recovering alcoholic)
  brief intervention (5-15 minute physician-delivered message)
 usual care
o 140 patients available for followup
o abstinence rates 6 months after hospital discharge (p = 0.006 across groups)
 64% with peer intervention (p = 0.013, NNT 4 vs. usual care)
 51% with brief intervention (p not reported vs. usual care, NNT 7 vs. usual care)
 36% with usual care
o Reference - J Fam Pract 2001 May;50(5):447 EBSCOhost Full Text full-text
 text message alcohol intervention with feedback might reduce binge drinking in young
adults in emergency department with prior hazardous alcohol use (level 2 [mid-level]
evidence)
o based on randomized trial with high loss to follow-up
o 765 adults aged 18-24 years in emergency department who screened positive for past hazardous
alcohol use were randomized to 1 of 3 interventions for 12 weeks
 text message intervention with drinking-related queries and real-time feedback twice weekly
(assessing weekend plans for drinking on Thursday and to report weekend alcohol
consumption on Sunday)
 text messages of alcohol consumption queries once weekly (Sunday) without feedback
 no text message intervention (control)
o 78% completed web-based follow-up survey
o mean change in binge-drinking days
 -0.51 with text messages plus feedback (p < 0.05 vs. each other group)
 +0.9 with text message without feedback
 +0.41 with control
o consistent findings for change in number of drinks per drinking day
o Reference - Ann Emerg Med 2014 Dec;64(6):664 full-text
Brief interventions in college students:
 brief intervention associated with small decrease in alcohol consumption by college
students after 1 year (level 2 [mid-level] evidence)
o based on systematic review of trials with methodologic limitations
o systematic review of 18 randomized trials evaluating brief intervention in 6,233 college students
identified as high-risk drinkers
o brief intervention conducted over 1-2 sessions of 30-90 minutes each and included face-to-face
motivational interviewing and personalized feedback (similar to Brief Alcohol Screening
Intervention for College Students [BASICS])
o control included no intervention, usual care, or other alternative intervention
o all trials had ≥ 1 limitation including
 high loss to follow-up (≥ 20%)
 unclear allocation concealment
 unclear blinding of outcome assessors
 unclear randomization sequence generation
o after follow-up of 1 year, brief intervention associated with (compared to control)
 decrease in mean alcohol consumption (-1.5 drinks/week, 95% CI -3.24 to -0.29) in analysis
of 12 trials, analysis limited by significant heterogeneity
 decrease in alcohol-related problems (as assessed by Rutgers Alcohol Problem Index) in
analysis of 11 trials, analysis limited by significant heterogeneity
o Reference - Subst Abuse Treat Prev Policy 2012 Sep 12;7(1):40 full-text
 brief motivational interviews may reduce alcohol consumption at 1 month but not at 12
months in college students (level 2 [mid-level] evidence)
o based on randomized trial with high loss to follow-up
o 677 college students (64% male) with residence hall alcohol violations randomized to 1 of 4
groups with follow-up at 1, 6, and 12 months
 30-148 minute (mean 62 minutes) brief motivational intervention, including in-person
interview with personalized drinking patterns feedback, typical and peak blood alcohol
concentration (BAC), alcohol-related consequences and risk behaviors, personalized goal
setting, and tips for safer drinking
  60 minute interactive computer program including alcohol-related decision making at virtual
party, factors affecting BAC in virtual bar, alcohol knowledge test in virtual game show
 120 minute internet-based education consisting of 5 chapters, quiz questions, interactive
exercises, and journaling opportunities
 1-month delayed intervention (control)
o 78% completed 2 follow-ups
o brief motivational intervention associated with reduced alcohol consumption at 1 month
compared to other groups
o no significant differences in alcohol consumption among all groups at 12 months
o Reference - Addiction 2011 Mar;106(3):528 EBSCOhost Full Text, commentary can be
found in Addiction 2011 Aug;106(8):1534 EBSCOhost Full Text,Addiction 2011
Oct;106(10):1871 EBSCOhost Full Text
 motivational interview with feedback associated with reduced alcohol consumption by
college students
o based on randomized trial of 279 heavy drinkers comparing web feedback only vs. single
motivational session with or without feedback vs. assessment only
o Reference - J Consult Clin Psychol 2009 Feb;77(1):64 full-text
 inconsistent evidence for efficacy of web or computer-based interventions for college students in 3
trials by same authors
o computer-based screening and brief intervention associated with reduction in alcohol
consumption and alcohol-related academic problems for up to 1 year in students with
hazardous or harmful drinking (level 2 [mid-level] evidence)
 based on randomized trial with wide confidence intervals
 576 university students aged 17-29 years with hazardous or harmful drinking on Alcohol Use
Disorders Identification Test (AUDIT) screening in New Zealand were randomized to 1 of 4
groups
 single-dose electronic-screening and brief intervention group (Web-based motivational
intervention) in university health center waiting room
 multidose electronic-screening and brief intervention group (Web-based motivational
intervention with further interventions 1 and 6 months later)
 information pamphlet alone (control)
 147 (25.5%) randomized to alternative control group and not analyzed in this article
 of 429 patients randomized to 3 groups analyzed
 360 (84%) included in 6-month analysis
 360 (84%) included in 12-month analysis
 intervention groups reported statistically significant decreases in frequency of drinking, total
alcohol consumption, and academic problems at 6 months
 intervention groups also reported statistically significant decrease in academic problems at
12 months
 other outcomes had statistically significant differences favoring intervention, but wide
confidence intervals limit conclusions about magnitude of benefit for any outcome
 Reference - Arch Intern Med 2008 Mar 10;168(5):530 full-text
o brief Web-based alcohol intervention may reduce quantity and frequency of drinking
in college students (level 2 [mid-level] evidence)
 based on randomized trial with high dropout rate
 2,435 undergraduate college students aged 17-24 years in Australia who scored in
hazardous/harmful range (AUDIT score ≥ 8) on Web-based screening were randomized to
Web-based alcohol intervention vs. screening only
 brief motivational Web-based alcohol intervention given immediately following screening
included
 explanation of AUDIT score and associated health risk with risk reduction information
 estimate of blood alcohol level for heaviest drinking episode in last 4 weeks and
information about related risks
 estimates of monetary expenditures per month and year
 bar graphs of drinking norms
 links to websites for smoking cessation and help with drinking problems
 78% had 1-month follow-up and 65% had 6-month follow-up
  intervention associated with
 reduced drinking frequency at 1 month and 6 months
 reduced volume of alcohol consumed at 1 month and 6 months
 reduced risk of chronic harm from heavy drinking at 1 month and 6 months
 no significant difference between groups in risk of binge drinking at 1 month or 6 months
 Reference - Arch Intern Med 2009 Sep 14;169(16):1508
o Web-based alcohol screening and brief intervention might not reduce alcohol
consumption in university students (level 2 [mid-level] evidence)
 based on randomized trial without intention-to-treat analysis
 3,422 university students aged 17-24 years in New Zealand with hazardous or harmful
alcohol use (AUDIT-consumption score ≥ 4) randomized to 1 of 2 interventions and followed
for 5 months
 Web-based alcohol screening and brief intervention consisting of assessment and
personalized feedback (including comparisons with medical guidelines and normal
values) on alcohol expenditure, peak blood alcohol concentration, alcohol dependence,
and access to help and information for 10 minutes
 screening only (control)
 34% consumed ≥ 2 alcoholic drinks per week at baseline
 83% completed follow-up and were included in primary analyses
 no significant differences in frequency of drinking, overall drinking, risk of binge drinking, or
academic problems after adjustment of p value for significance to account for multiple
comparisons
 median number of drinks consumed per drinking session was 4 in intervention group vs. 5 in
control group (p = 0.005)
 Reference - JAMA 2014 Mar 26;311(12):1218, editorial can be found in JAMA 2014 Mar
26;311(12):1207
Longer-term interventions:
 motivational interviewing might reduce extent of substance use compared to no
intervention (level 2 [mid-level] evidence)
o based on Cochrane review of trials with methodologic limitations
o systematic review of 59 trials evaluating motivational interviewing in 13,342 patients with alcohol
use or drug use disorders
 29 trials had unclear allocation concealment
 32 trials had unclear or inadequate incomplete outcome data
 31 trials had unclear blinding of assessors
 1 trial had high loss to follow-up
o comparing motivational interviewing to no treatment
 motivational interviewing associated with decreased extent of substance use
 post-intervention (p < 0.0001) in analysis of 4 trials with 231 patients
 at 1-6 months (p = 0.0001) in analysis of 15 trials with 2,327 patients
 at 7-12 months (p = 0.0055) in analysis of 12 trials with 2,326 patients
 no significant difference in substance use at long-term (mean 12 months) follow-up in 1 trial
with 363 patients
o no significant differences comparing motivational interviewing vs. treatment as usual in extent of
substance use
 postintervention in analysis of 9 trials with 1,495 patients
 at 1-6 months in analysis of 10 of trials with 2,102 patients
 at 7-12 months in analysis of 5 trials with 890 patients
o comparing motivational interviewing to assessment and feedback
 no significant difference in extent of substance use at 1-6 months in analysis of 7 trials with
986 patients
 motivational interviewing associated with decreased extent of substance use (p = 0.0074) at
7-12 months in analysis of 2 trials with 265 patients
o no significant differences comparing motivational interviewing vs. other active intervention (for
example, education or other counseling) in extent of substance use
 postintervention in analysis of 2 trials with 185 patients
 at 1-6 months in analysis of 12 trials with 2,137 patients
  at 7-12 months in analysis of 6 trials with 1,586 patients
 at long-term follow-up (mean 12 months) in analysis of 2 trials with 437 patients
o Reference - Cochrane Database Syst Rev 2011 May 11;(5):CD008063
 cognitive behavioral therapy associated with increased abstinence, but focus and
duration of sessions may influence effectiveness (level 2 [mid-level] evidence)
o based on randomized trial with low adherence
o 284 patients with depression and hazardous alcohol consumption were offered single cognitive
behavioral therapy session then randomized to 9 alcohol-related sessions vs. 9 depression-related
sessions vs. 9 integrated depression and alcohol-related sessions vs. no further treatment
o average attendance 5.76 sessions
o multiple sessions significantly associated with
 greater reduction in average drinks and drinking days
 greater reduction in depressive symptoms
o integrated treatment associated with greater overall reduction in drinking days and level of
depression
o greater improvements observed in men with
 alcohol-related sessions vs. depression-related sessions (greater reduction in number of daily
drinks, mean change 4.62 vs. 0.34)
 single-focused sessions vs. integrated sessions (greater improvement in functioning scores)
o greater improvements observed in women with
 depression-related sessions vs. alcohol-related sessions (greater reduction in number of daily
drinks, mean change 4.22 vs. 0.24)
 integrated sessions vs. single-focused sessions (greater improvement in functioning scores)
o Reference - Addiction 2010 Jan;105(1):87 EBSCOhost Full Text
 cognitive behavioral therapy and primary care management have similar abstinence rates
at 10 weeks in patients taking naltrexone (level 2 [mid-level] evidence)
o based on randomized trial without intention-to-treat analysis
o 197 patients taking naltrexone 50 mg daily randomized to cognitive behavioral therapy vs.
primary care management
o cognitive behavioral therapy provided as 1.25-hour initial session then 9 weekly 50-minute
sessions
o primary care management provided as 45-minute initial visit then 7 visits lasting 15-20 minutes
each over 10 weeks
o 171 patients included in analysis
o heavy drinking ≤ 2 days during last 28 days 86.5% with cognitive behavioral therapy vs. 84.1%
with primary care management (not significant)
o Reference - Arch Intern Med 2003 Jul 28;163(14):1695 full-text
 cognitive behavioral therapy plus motivational interviewing associated with slightly
reduced extent of alcohol use and modest improvement in symptoms of depression (level
2 [mid-level] evidence)
o based on systematic review with unclear clinical significance
o systematic review of 9 randomized trials and 3 cohort studies comparing cognitive behavioral
therapy plus motivational interviewing to brief intervention or usual care in 1,721 patients with
alcohol use disorder and comorbid depression
o outcomes reported using mean effect sizes, with 0.2 considered a small effect
o cognitive behavioral therapy plus motivational interviewing associated with reduced
 alcohol consumption (mean effect size 0.17, 95% CI 0.07-0.28)
 severity of depressive symptoms (mean effect size 0.27, 95% CI 0.13-0.41)
o Reference - Addiction 2014 Mar;109(3):394 EBSCOhost Full Text
 motivational enhancement, cognitive-behavioral therapy, and facilitating the patient’s
entry and retention in Alcoholics Anonymous appear to be equally effective at
maintaining abstinence (level 2 [mid-level] evidence)
o almost 30% of patients abstinent in year 3 of study
o patients who reported drinking drank on average 1 out of 3 days
o no approach was superior at 3 years
o Reference - Project MATCH (Alcohol Clin Exp Res 1998 Sep;22(6):1300)
 o criticism can be found in BMC Public Health 2005 Jul 14;5:75, commentary can be found in BMC
Public Health 2005 Jul 18;5:76
 social behavior and network therapy as effective as motivational enhancement therapy
for reducing alcohol related problems at 1-year follow-up (level 1 [likely reliable]
evidence)
o based on randomized trial
o 742 patients with alcohol problems randomized to social behavior and network therapy (cognitive
and behavioral strategies to help patients build social networks supportive of change, 8 sessions
lasting 50 minutes over 8-12 weeks) vs. motivational enhancement therapy (3 sessions lasting 50
minutes over 8-12 weeks)
o follow up completed by 689 (93%) at 3 months and 617 (83%) at 1 year
o both groups had similar substantial reductions in alcohol consumption, dependence and alcohol-
related problems and had similar improvements in mental health-related quality of life
o only significant difference was better physical health at 3 months with social behavioral and
network therapy, but single significant difference may be due to chance
o Reference - BMJ 2005 Sep 10;331(7516):541 full-text
o cost effectiveness did not differ between therapies (BMJ 2005 Sep 10;331(7516):544 full-text)
o editorial can be found in BMJ 2005 Sep 10;331(7516):527
 integrated medical and substance abuse treatment appears to improve abstinence rates
at 6 months in patients with substance abuse-related medical conditions (level 2 [mid-
level] evidence)
o based on subgroup analysis of randomized trial
o 592 patients with alcohol or other substance abuse randomized to integrated care (primary
healthcare included with addiction treatment program) vs. usual care (separate primary care and
substance abuse treatment), both programs group-based for 8 weeks with 10 months of
aftercare
o abstinence rates comparing integrated care vs. usual care
 58% vs. 63% overall (not significant)
 66% vs. 73% in subgroup of patients without substance abuse-related medical conditions
(not significant)
 69% vs. 55% in subgroup of 341 patients with substance abuse-related medical conditions
(p = 0.006, NNT 8), findings significant both for patients with medical conditions and
psychiatric conditions
o Reference - JAMA 2001 Oct 10;286(14):1715 full-text, editorial can be found in JAMA 2001 Oct
10;286(14):1764
 network support might increase abstinence rates (level 2 [mid-level] evidence)
o based on randomized trial without intention-to-treat analysis and with mixed statistical results
o 210 participants with alcohol dependence randomized to 1 of 3 groups
 case management - active control, attendance at Alcoholics Anonymous neither encouraged
nor discouraged
 network support - twelve 1-hour sessions to help patient change social network to one more
supportive of abstinence and less supportive of drinking, attendance at Alcoholics
Anonymous encouraged
 network support plus contingency management - network support plus prize drawing if
verified completion of assigned tasks
o 186 (88.6%) followed for 15 months
o comparing case management vs. network support vs. network support plus contingency
management
 proportion of days abstinent at 15 months (estimated from Figure 2) was about 60% vs.
75% vs. 70%
 proportion of patients abstinent for prior 90 days at 15 months (estimated from Figure 2)
was about 22% vs. 40% vs. 28%
o statistical significance for abstinence outcomes varied
 proportion of days abstinent through 15 months not statistically significant in comparisons of
treatment groups, but both network support groups statistically superior to control in
planned time × treatment analysis
  proportion of patients abstinent for prior 90 days not statistically significant in comparisons of
treatment groups (adjusting for other factors), but network support statistically superior to
control in a posteriori analysis
o network support did not affect social support for drinking but appeared to increase behavioral
and attitudinal support for abstinence
o Reference - J Consult Clin Psychol 2007 Aug;75(4):542
o network support alone associated with mean 80% days abstinent compared to just over 60% in
other groups at 2 years posttreatment (J Consult Clin Psychol 2009 Apr;77(2):229 full-text)
 stepped care appears no more effective than minimal intervention for reducing alcohol
consumption (level 2 [mid-level] evidence)
o based on randomized trial without intention-to-treat analysis
o 112 male patients scoring ≥ 8 on Alcohol Use Disorders Identification Test were randomized to
stepped care intervention vs. 5 minutes of minimal intervention delivered by practice nurse and
followed for 6 months
o stepped care consisted of 3 successive steps
 1 session of behavior change counseling delivered by practice nurse
 four 50-minute sessions of motivational enhancement therapy delivered by trained alcohol
counselor
 referral to community alcohol treatment agency
o 80.4% included in analysis
o no significant difference in reduction of alcohol consumption between treatments
o Reference - Br J Psychiatry 2009 Nov;195(5):448
 stepped care may not reduce alcohol consumption compared to minimal intervention
(level 2 [mid-level] evidence)
o based on randomized trial with low compliance
o 529 adults ≥ 55 years old with alcohol use disorder (defined as score ≥ 8 on Alcohol Use
Disorders Identification test) randomized to 1 of 2 interventions and followed for 12 months
 stepped care intervention consisting of initial behavioral change counselling session for 20
minutes followed by referral to motivational enhancement therapy followed by local specialist
alcohol services as needed
 brief advice intervention for 5 minutes with practice or research nurse discussing health
consequences of continued hazardous alcohol consumption
o 28% in stepped care group who were referred to motivational enhancement therapy attended
o no significant differences in mean drinks per day consumed, alcohol-related problems, health-
related quality of life, or overall healthcare costs
o Reference - AESOPS trial (Health Technol Assess 2013 Jun;17(25):1 PDF)
 couple therapy
o alcohol behavioral couple therapy associated with reduction in days of drinking
compared to individual therapy in females with alcohol use disorder (level 2 [mid-
level] evidence)
 based on randomized trial with allocation concealment not stated
 102 heterosexual women with alcohol use disorder randomized to alcohol behavioral couple
therapy vs. individual therapy for 6 months and followed for 1 year
 couple therapy associated with significant increase in percentage of days abstinent and
percentage of days of heavy drinking through end of follow-up
 Reference - PREMIER trial (J Consult Clin Psychol 2009 Apr;77(2):243)
o addition of behavioral couples therapy to weekly individual counseling may reduce
days of drinking and partner violence in married female alcoholics at 12-month
follow-up (level 2 [mid-level] evidence)
 based on randomized trial with allocation concealment not stated
 138 married and cohabiting female alcoholics treated with 20 weekly individual counseling
sessions focused on 12-step facilitation and randomized to 12 additional weekly sessions
(weeks 5-16) of 1 of 3 types
 behavioral couples therapy involving active partner participation
 additional individual counseling sessions (twice weekly instead of once weekly)
 lectures about substance abuse with partner attendance
 22 women (16%) lost to follow-up
 Behavioral Couples Additional Individual
Outcomes Therapy Counseling Lectures
Mean % days abstinent pretreatment 44% 41% 44%

Mean % days abstinent posttreatment 96% 94% 95%

Mean % days abstinent at 12 months

(statistical comparison not reported) 79% 60% 62%

Mean number of days of male-to-female any

violence in prior year pretreatment 4.7 5 6

Mean number of days of male-to-female any

violence over 12 months 1.7* 3.4 3.9

Mean number of days of female-to-male any

violence in prior year pretreatment 6.9 6 7.3

Mean number of days of female-to-male any

violence over 12 months 1.7* 4 3.1*

* p < 0.05 for behavioral couples therapy vs. either of other interventions
Comparison of Interventions:
 Reference - J Consult Clin Psychol 2006 Jun;74(3):579
 additional treatment (life-skill training and booster sessions) following drinking reduction
treatment may further reduce drinking in women who are heavy drinkers (level 2 [mid-
level] evidence)
o based on subgroup analysis in randomized trial
o 144 women ≥ 21 years of age consuming ≥ 15 drinks per week or having ≥ 2 drinking days (6 or
more drinks per day) per week were given drinking reduction treatment for 13 hours and
randomized to 1 of 4 groups
 no additional treatment (control group)
 additional 7 hours of life-skills training
 additional booster sessions of drinking reduction treatment at 2, 4, 7, 10, 13, 16, 20, and 24
weeks
 additional life-skills training and booster sessions of drinking reduction treatment
o number of abstinent or light drinking days (1-3 standard drink equivalents) were recorded over
18 months
o mean number of abstinent or light drinking days per month in subgroup of women who were
heavier drinkers at baseline (≤ 18.4 abstinent or light drinking days per month)
 18 in control group
 22 in life-skills training group
 19.9 in booster sessions group
 26.8 in combination group (p < 0.01 compared to other groups)
o no significant differences in subgroup of women who were lighter drinkers at baseline (> 18.4
abstinent or light drinking days per month)
o Reference - J Consult Clin Psychol 2001 Jun;69(3):447
o similar results reported at 30-month follow-up (J Consult Clin Psychol 2007 Jun;75(3):501)
 combined behavioral intervention is modestly effective for reducing alcohol use, similar
efficacy as naltrexone, no added efficacy for combination withnaltrexone (level 1 [likely
reliable] evidence)
o combined behavioral intervention provided in up to 20 sessions lasting 50 minutes integrating
aspects of cognitive behavioral therapy, 12-step facilitation, motivational interviewing and support
system involvement
o based on 9-way randomized trial with 1,383 patients (COMBINE study)
 nurse-led health promotion group sessions may be as effective as therapist-led
motivational interviewing in reducing alcohol use in patients in methadone maintenance
program (level 2 [mid-level] evidence)
o based on randomized trial
 o 256 methadone-maintained patients with moderate to heavy alcohol use randomized to 1 of 3
conditions
 nurse-led hepatitis health promotion group sessions
 therapist-led motivational interviewing in group sessions
 therapist-led motivational interviewing in 1-on-1 sessions
o significant reduction in self-reported alcohol use in all groups (from median 90 drinks/month at
baseline to 60 drinks/month at 6 months)
o no significant differences in self-reported alcohol use in comparisons by condition
o Reference - Drug Alcohol Depend 2010 Feb 1;107(1):23
 addition of family motivational interview to brief individual motivational interview may
not further reduce alcohol use in adolescents (level 2 [mid-level] evidence)
o based on randomized trial with high dropout rate
o 125 adolescents aged 13-17 years treated in emergency department after alcohol-related event
were randomized to family motivational interview plus brief individual motivational interview vs.
brief individual motivational interview alone and followed for 12 months
o 66.4% completed study
o both treatments significantly reduced drinking frequency, quantity and frequency of high-volume
drinking compared to baseline
o no significant differences between treatments in drinking frequency, quantity and frequency of
high-volume drinking at 12 months follow-up
o Reference - Arch Pediatr Adolesc Med 2011 Mar;165(3):269
 review of realistic approaches to counseling in office setting can be found in Am Fam Physician 2009
Feb 15;79(4):277
 United States Substance Abuse and Mental Health Services Administration guideline on group therapy
in substance abuse treatment can be found at SAMHSA 2005 PDF
Computer-based interventions:
 nonguided computer-based interventions may reduce alcohol consumption in adults
compared to minimally active interventions (level 2 [mid-level] evidence)
o based on systematic review with incomplete assessment of trial quality
o systematic review of 24 randomized trials comparing nonguided computer-based interventions vs.
minimally active interventions (assessment-only, usual care, generic non-tailored information or
education material) or brief interventions for reducing alcohol consumption in adults
o allocation concealment was only source of bias assessed, 3 trials had adequate concealment
o compared to minimally active interventions, nonguided computer-based interventions associated
with reduced
 alcohol consumption in students (mean difference -19.42 g/week, 95% CI -29.83 to -9
g/week) in analysis of 12 studies
 alcohol consumption in nonstudents (mean difference -114.94 g/week, 95% CI -198.6 to -
31.29 g/week) in analysis of 4 studies, results limited by heterogeneity (p = 0.005)
 binge drinking in students (mean difference -0.23 days/week, 95% CI -0.47 to 0 days/week)
in analysis of 5 trials
o Reference - Addiction 2011 Feb;106(2):267 EBSCOhost Full Text
 self-directed or telephone-based cognitive behavioral therapy may be effective for
reducing substance and/or alcohol misuse in adults (level 2 [mid-level] evidence)
o based on systematic review without assessment of trial quality
o systematic review of health technology assessments, systematic reviews, and randomized trials
evaluating self-directed or telephone-based cognitive behavioral therapy (CBT) in adults with
alcohol and/or drug dependence or gambling addiction
o review included 4 randomized trials evaluating self-directed or telephone-based CBT in patients
with alcohol and/or drug dependence
 decreased substance and/or alcohol use with
 biweekly access to computer-based training in CBT skills vs. treatment as usual in 1 trial
with 73 adults with multiple substance use
 web-based, interactive self-help CBT intervention vs. online brochure on alcohol use in 1
trial with 261 adults with alcohol use disorder
 telephone-based CBT for continuing care vs. intensive face-to-face intervention in 1 trial
with 359 adults with alcohol and/or cocaine dependence
  no significant differences in depression and substance use comparing computer-delivered
CBT vs. psychologist-delivered CBT in 1 trial with 97 adults with comorbid depression and
alcohol or cannabis misuse
o Reference - Canadian Agency for Drugs and Technologies in Health (CADTH) Technology
Overview 2010 Dec PDF
 web-based protocol might increase abstinence in nondependent problem drinkers (level 2
[mid-level] evidence)
o based on randomized trial without intention-to-treat analysis
o 80 nondependent problem drinkers randomized to web-based protocol to promote moderate
drinking vs. control
o web-based protocol associated with significant increase in days abstinent at 12 months
o protocol can be found at www.moderatedrinking.com
o Reference - J Consult Clin Psychol 2011 Apr;79(2):215 full-text
Medications:
 pharmacologic interventions considered primarily as adjunct therapy for patients receiving psychosocial
interventions (J Subst Abuse Treat 2009 Jan;36(1):S15)
Disulfiram:
 disulfiram (Antabuse) is an aldehyde dehydrogenase inhibitor which acts as alcohol deterrent by
producing unpleasant symptoms with small amounts of alcohol
 never give to patient in state of alcohol intoxication or without patient's knowledge
 FDA approved for management of alcohol dependence in selected, highly motivated patients in
conjunction with supportive and psychotherapeutic treatment
 dosing
o initial dose 500 mg orally once daily for 1-2 weeks
o may reduce dose if sedation occurs, range 125-500 mg daily
o treatment may be required for months or years
 caution in elderly or patients with hepatic or renal impairment
 avoid concomitant use with alcohol, isoniazid, metronidazole and possibly phenytoin
 contraindicated if severe myocardial disease, coronary occlusion or psychosis
 Pregnancy Category C
 adverse effects include hepatitis, hepatic failure, skin eruptions, drowsiness, fatigue, erectile
dysfunction, headache, metallic or garlic-like aftertaste, psychotic reactions
 see also Disulfiram
 disulfiram may reduce alcohol consumption in patients with alcohol dependence (level 2
[mid-level] evidence)
o based on systematic review of low-to-moderate quality trials
o systematic review of 22 randomized trials comparing disulfiram vs. any control in 2,414 patients
with alcohol dependence
o comparators included placebo, no disulfiram, naltrexone, acamprosate, and topiramate
o disulfiram associated with
 decreased alcohol consumption in analysis of all trials, results suggest possibly greater
benefit with supervised medication intake compared to unsupervised medication intake
 increased rate of adverse events (rate ratio 1.4, 95% CI 1-1.94) in analysis of 14 trials
o Reference - PLoS One 2014;9(2):e87366 EBSCOhost Full Text full-text
 disulfiram may reduce days of drinking but not improve total abstinence at 1 year (level 2
[mid-level] evidence)
o based on randomized trial with partial blinding and low compliance rates
o 605 male alcoholics randomized to 250 mg of disulfiram vs. 1 mg of disulfiram vs. 50 mg
riboflavin
o all patients knew if they received disulfiram or riboflavin but were blinded to dosages of disulfiram
to test role of patient's fear of disulfiram-ethanol reaction
o providers were blinded to all treatment groups
o 577 patients analyzed for most results
Disulfiram 250 Disulfiram 1 Placebo (Riboflavin 50
mg mg mg)
Abstinence at 1 year (by intention-to-treat 18.8% 22.5% 16.1%
 Disulfiram 250 Disulfiram 1 Placebo (Riboflavin 50
mg mg mg)
analysis)

Days to first drink 54.2 65.0 40.7

Mean days of drinking (patient report) 49.0* 75.4 86.5

Compliant with treatment 23% 17% 18%

Abstinence among compliant patients 38% 50% 43%

Abstinence among compliant patients 38% 50% 6%

* p < 0.05 for difference in disulfiram 250 mg group vs. either of other groups
Treatment Comparisons:
o low compliance rates (measured by urine tests) suggests limits of clinical usefulness
o Reference - JAMA 1986 Sep 19;256(11):1449
Naltrexone:
 opiate antagonist
 available orally (Depade, ReVia, generic) and for intramuscular use (Vivitrol)
 FDA approved for adjunctive use with medically supervised behavior modification program in
treatment of opiate dependence or alcohol dependence
 typical maintenance dosing 50 mg orally once daily in absence of opiates (smaller doses may be used
initially following opiate cessation)
 naltrexone 380 mg intramuscularly every 4 weeks is an alternative route for treatment of alcohol
dependence in patients free of opiates
 naltrexone challenge test recommended in patients who may be physically dependent on opiates
 contraindicated if taking opiate agonists, experiencing opiate withdrawal, acute hepatitis or hepatic
failure
 adverse effects include hepatotoxicity, insomnia, anxiety, nervousness, nausea, vomiting, headache,
fatigue
 Pregnancy Category C
 see also Naltrexone
 naltrexone may reduce heavy drinking and relapse rate in alcohol dependent patients
(level 2 [mid-level] evidence)
o based on 2 systematic reviews limited by heterogeneity
o Cochrane review of 50 randomized trials of opioid antagonists in 7,793 patients with alcohol
dependence
 47 trials evaluated naltrexone, 3 trials evaluated nalmefene
 naltrexone compared to placebo
 reduced risk of heavy drinking in analysis of 28 trials with 4,433 patients
 risk ratio (RR) 0.83 (95% CI 0.76-0.9)
 NNT 7-17 assuming 61% heavy drinking in placebo group
 results limited by significant heterogeneity (p < 0.0001)
 reduced risk of any drinking in analysis of 27 trials with 4,693 patients
 RR 0.96 (95% CI 0.92-1.00)
 results limited by significant heterogeneity (p = 0.09)
 decreased drinking days in analysis of 26 trials with 3,882 patients
 mean difference -3.89 (95% CI -5.75 to -3.81)
 results limited by significant heterogeneity (p < 0.0001)
 decreased heavy drinking days in analysis of 15 trials with 1,715 patients
 mean difference -3.25 (95% CI -5.51 to -0.99)
 results limited by significant heterogeneity (p < 0.0001)
 side effects significantly more common with naltrexone included abdominal pain,
decreased appetite, nausea, vomiting, daytime sleepiness, drowsiness, fatigue,
insomnia, lethargy, somnolence, weakness, blurred vision, decreased libido, depression,
dizziness, and nightmares
 at 3-12 months after treatment discontinued
  reduced risk of heavy drinking in analysis of 5 trials with 1,061 patients
 RR 0.86 (95% CI 0.75-0.99)
 NNT 6-130 assuming 77% heavy drinking in placebo group
 results limited by significant heterogeneity (p = 0.1)
 no significant difference in risk of any drinking in analysis of 2 trials with 185
patients
 RR 0.94 (95% CI 0.79-1.11)
 injectable naltrexone appears effective, based on analysis of 4 trials, but not all outcomes
were statistically significant
 naltrexone compared to acamprosate in 3 trials
 no significant differences in efficacy in metaanalysis
 naltrexone associated with more nausea and somnolence, acamprosate associated with
more diarrhea
 no significant differences in efficacy single trials comparing naltrexone to aripiprazole,
nefazodone, or topiramate
 nalmefene may be effective, but results did not reach statistical significance in analysis of 3
trials with 396 patients
 Reference - Cochrane Database Syst Rev 2010 Dec 8;(12):CD001867
o systematic review of 122 randomized trials and 1 cohort study evaluating efficacy of
pharmacotherapy for alcohol use disorder in 22,803 adult outpatients
 all trials had treatment duration 12-52 weeks
 most trials enrolled patients following detoxification or required sobriety period ≥ 3 days and
included psychosocial co-interventions
 44 trials compared naltrexone vs. placebo
 study-specific quality measures not reported
 naltrexone 50 mg/day orally associated with significantly
 reduced risk of return to heavy drinking in analysis of 19 trials with 2,875 patients,
results limited by significant heterogeneity
 reduced risk of return to any drinking in analysis of 16 trials with 2,347 patients, results
limited by significant heterogeneity
 insufficient evidence to assess efficacy of naltrexone 100 mg/day orally or naltrexone
subcutaneously
 naltrexone (any formulation) associated with significantly increased risk of withdrawal for
adverse events in analysis of 17 trials with 2,743 patients
 Reference - JAMA 2014;311(18):1889, editorial can be found in JAMA 2014;311(18):1861
 naltrexone may reduce alcohol use in patients with posttraumatic stress disorder and
alcohol dependence (level 2 [mid-level] evidence)
o based on randomized trial with high loss to follow-up
o 165 patients with posttraumatic stress disorder (PTSD) and alcohol dependence were randomized
to
 naltrexone 100 mg/day vs. placebo for 24 weeks
 prolonged exposure therapy plus supportive counseling vs. supportive counseling alone for
24 weeks
o at baseline all patients had
 PTSD Symptom Severity Interview score ≥ 15 and heavy drinking within past 30 days
(defined as > 12 alcoholic drinks/week with ≥ 1 day with ≥ 4 drinks)
 prior outpatient medical detoxification (≥ 3 consecutive days without alcohol)
with oxazepam given as needed
o 32% were lost to follow-up but all patients were included in intention-to-treat analyses
o naltrexone associated with decrease in days of drinking and reduced alcohol cravings vs. placebo
(p = 0.008 for each)
o no significant differences in drinking behaviors comparing prolonged exposure therapy vs.
supportive counseling
o no significant differences in PTSD symptoms among groups
o Reference - JAMA 2013 Aug 7;310(5):488, editorial can be found in JAMA 2013 Aug 7;310(5):482
Acamprosate:
 acamprosate (Campral) 666 mg (2 tablets) orally 3 times daily with meals
 o start as soon as possible after achieving abstinence
o use 333 mg 3 times daily if creatinine clearance 30-50 mL/minute
o do not use if creatinine clearance < 30 mL/minute
 can be used in combination with naltrexone or disulfiram, different mechanism of action
 diarrhea and asthenia are common adverse effects
 suicide and suicidality have been reported
 low potential for significant drug interactions
 see also Acamprosate
 acamprosate may reduce risk of return to any drinking but not reduce risk of return to
heavy drinking in adult outpatients with alcohol use disorder (level 2 [mid-level]
evidence)
o based on systematic review with study-specific quality measures not reported
o systematic review of 122 randomized trials and 1 cohort study evaluating efficacy of
pharmacotherapy for alcohol use disorder in 22,803 adult outpatients
o all trials had treatment duration 12-52 weeks
o most trials enrolled patients following detoxification or required sobriety period ≥ 3 days and
included psychosocial co-interventions
o 22 trials compared acamprosate vs. placebo
o comparing acamprosate to placebo
 no significant difference in return to heavy drinking in analysis of 16 trials with 4,847 patients
 acamprosate associated with
 reduced risk of return to any drinking (p < 0.001) in analysis of 16 trials with 4,847
patients, analysis limited by significant heterogeneity
 fewer drinking days in analysis of 13 trials with 4,485 patients
o Reference - JAMA 2014 May 14;311(18):1889, editorial can be found in JAMA 2014 May
14;311(18):1861
 acamprosate may reduce risk of any drinking after completion of detoxification in alcohol
dependent patients (level 2 [mid-level] evidence)
o based on Cochrane review limited by heterogeneity
o systematic review of 24 randomized trials evaluating acamprosate in 6,894 alcohol-dependent
patients after completing detoxification
o patients mostly men (median age 42 years)
o study drugs were acamprosate in 2,563 patients, placebo in 2,929 patients and naltrexone in 402
patients
o acamprosate compared to placebo
 reduced risk of any drinking in analysis of 24 trials with 6,172 patients
 risk ratio 0.86 (95% CI 0.81-0.91)
 NNT 9 (95% CI 7-15)
 results limited by significant heterogeneity (p < 0.0001)
 increased percent of days abstinent in analysis of 19 trials with 5,224 patients
 mean difference +10.94% (95% CI +5.08% to +16.81%)
 results limited by significant heterogeneity (p < 0.0001)
 increased risk of diarrhea in analysis of 16 trials with 4,486 patients
 risk difference 0.11 (95% CI 0.09-0.13)
 NNH 9 (95% CI 8-12)
 results limited by significant heterogeneity (p < 0.0001)
 lower risk of dropouts overall (risk ratio 0.91, 95% CI 0.83-0.99) but higher risk of dropouts
due to adverse events (risk ratio 1.35, 95% CI 1.01-1.8)
 no significant difference in return to heavy drinking in analysis of 6 trials with 2,132 patients
o Reference - Cochrane Database Syst Rev 2010 Sep 8;(9):CD004332
Anticonvulsants:
 anticonvulsants may reduce alcohol consumption in adults with alcohol dependence (level
2 [mid-level] evidence)
o based on Cochrane review with confidence intervals including clinically unimportant differences
o systematic review of 25 randomized trials or controlled clinical trials evaluating anticonvulsants in
2,641 adults with alcohol dependence
 o anticonvulsants included topiramate (10 trials), gabapentin (5 trials), valproate (3
trials), levetiracetam (2 trials), oxcarbazepine (2 trials), zonisamide (1 trial), carbamazepine(1
trial), pregabalin (1 trial), and tiagabine (1 trial)
o comparing anticonvulsants to placebo
 no significant difference in risk of heavy drinking in analysis of 5 trials with 330 adults
 anticonvulsants associated with
 fewer drinks/drinking day (mean difference [MD] -1.49 drinks/drinking day, 95% Cl -
2.32 to -0.65 drinks/drinking day) in analysis of 11 trials with 1,126 adults
 increased dizziness in analysis of 6 trials with 882 adults
 risk ratio 1.98 (95% CI 1.28-3.06)
 NNH 7-57 with dizziness in 6% of placebo group
 no significant differences in time to first relapse and dropout
o comparing anticonvulsants to naltrexone
 anticonvulsants associated with
 fewer heavy drinking days (MD -5.21 days, 95% CI -8.58 to -1.83 days) in analysis of 3
trials with 308 adults
 longer time to severe relapse (MD 11.88 days, 95% CI 3.29-20.46 days) in analysis of 3
trials with 244 patients
 for adverse effects
 anticonvulsants associated with decreased hypotension but increased paresthesia
 no significant differences in nausea, dizziness, and sedation
 no significant differences in dropout
o Reference - Cochrane Database Syst Rev 2014 Feb 13;(2):CD008544
Gabapentin:
 gabapentin associated with increased abstinence and reduced heavy drinking in adults
with alcohol dependence (level 2 [mid-level] evidence)
o based on randomized trial with high dropout rate
o 150 adults seeking treatment for alcohol dependence randomized to gabapentin 900 mg/day or
1,800 mg/day divided dose (3 times daily) vs. placebo and followed for 12 weeks
o all patients received manual-guided counseling
o 43% did not complete trial, but all patients randomized included in analyses
o rate of complete abstinence (p = 0.04 for trend)
 4.1 % for placebo
 11.1% for gabapentin 900 mg
 17% for gabapentin 1,800 mg
o rate of no heavy drinking (≥ 4 drinks per day for women and ≥ 5 drinks per day for men)(p =
0.02 for trend)
 22.5 % for placebo
 29.6% for gabapentin 900 mg
 44.7% for gabapentin 1,800 mg
o similar linear trend noted for relapse-related outcomes of mood (p = 0.001), sleep (p < 0.001),
and alcohol craving (p = 0.03)
o Reference - JAMA Intern Med 2014 Jan;174(1):70, editorial can be found in JAMA Intern Med
2014 Jan;174(1):78
Topiramate :
Topiramate prescribing information:
 topiramate (Topamax) FDA approved for seizures, and also for migraine prophylaxis in adults; generic
topiramate FDA approved to prevent seizures
 dose used in trials for alcohol use disorder was 25 mg once daily titrated to 150 mg twice daily
 reduce dose if renal impairment
 FDA Pregnancy Category D (based on data suggesting association between topiramate use and
increased risk of cleft lip and cleft palate in infants) (FDA Press Release 2011 Mar 4)
 adverse effect warnings include metabolic acidosis, cognitive/neuropsychiatric effects, withdrawal
seizures, acute myopia with secondary angle closure glaucoma, oligohidrosis, and hyperthermia
 avoid use in patients receiving other carbonic anhydrase inhibitors or on ketogenic diet due to
possible development of renal stones
 antiepileptic drugs associated with increased suicidality (suicidal behavior or ideation) (level 2 [mid-
level] evidence)
 multiple drug interactions
 monitor baseline and periodic serum bicarbonate
 monitor closely for oligohidrosis and hyperthermia, especially in children
 see Topiramate for additional information
Topiramate efficacy:
 topiramate may reduce drinking in adult outpatients with alcohol use disorder (level 2
[mid-level] evidence)
o based on systematic review with study-specific quality measures not reported
o systematic review of 122 randomized trials and 1 cohort study evaluating efficacy of
pharmacotherapy for alcohol use disorder in 22,803 adult outpatients
o all trials had treatment duration 12-52 weeks
o most trials enrolled patients following detoxification or required sobriety period ≥ 3 days
o most trials included psychosocial co-interventions
o 6 trials compared topiramate vs. placebo
o comparing topiramate to placebo, topiramate associated with significantly
 fewer drinking days in analysis of 2 trials with 541 patients
 fewer heavy drinking days (defined as ≥ 4-5 drinks per day) in analysis of 3 trials with 691
patients
 fewer drinks per drinking day in analysis of 3 trials with 691 patients
 increased risk of cognitive dysfunction, paresthesia, and taste abnormalities in analyses of
2-3 trials each
o Reference - JAMA 2014;311(18):1889, full report can be found at AHRQ Comparative
Effectiveness Review 2014 May:134 PDF, editorial can be found in JAMA 2014;311(18):1861
 topiramate (25 mg once daily titrated to 150 mg twice daily) may reduce heavy drinking
and may improve quality of life but often not tolerated (level 2 [mid-level] evidence)
o based on 2 randomized trials with high dropout rates
o topiramate may reduce heavy drinking but often not tolerated (level 2 [mid-level]
evidence)
 based on randomized trial with high dropout rate
 371 patients aged 18-65 years were randomized to topiramate (25 mg once daily titrated to
300 mg/day in 2 divided doses) vs. placebo for 14 weeks
 all patients had weekly Brief Behavioral Compliance Enhancement Treatment (BBCET)
intervention to emphasize medication adherence
 256 patients (69%) completed trial
 dropouts included in intention-to-treat analysis with assumption of relapse to heavy
drinking
 34 (18.6%) topiramate vs. 6 (3.2%) did not complete trial due to limiting adverse
event (NNH 6)
 37 (20.2%) topiramate vs. 38 (20.2%) did not complete trial for other reasons
 heavy drinking days defined as ≥ 5 standard drinks for men, ≥ 4 for women per day
 drinking reduction assessed weekly via self-reported patient diary and plasma gamma-
glutamyltransferase (GGT) levels measured at weeks 0, 4, 8, 12, and 14
 comparing topiramate vs. placebo at 14 weeks
 mean heavy drinking days 43.8% vs. 51.8% (p = 0.002) (absolute difference about 2.5
days/month)
 mean abstinent days 37.6% vs. 29.1% (p = 0.002)
 mean drinks/drinking day 6.5 vs. 7.5 (p = 0.006)
 patients achieving 28 or more days of continuous abstinence 14.8% vs. 3.2% (p <
0.001, NNT 9)
 patients achieving 28 or more days of continuous nonheavy drinking 29.5% vs. 14.9%
(p < 0.001, NNT 7)
 adverse events comparing topiramate vs. placebo
 paresthesia in 50.8% vs. 10.6% (p < 0.001, NNH 2)
 headache in 24% vs. 31.9% (p = 0.09)
 taste perversion in 23% vs. 4.8% (p < 0.001, NNH 5)
  fatigue in 22.4% vs. 17.6% (not significant)
 anorexia in 19.7% vs. 6.9% (p < 0.001, NNH 7)
 insomnia in 19.1% vs. 16% (not significant)
 difficulty with concentration or attention in 14.8% vs. 3.2% (p < 0.001, NNH 8)
 nervousness in 14.2% vs. 7.5% (p = 0.04, NNH 15)
 dizziness in 11.5% vs. 5.3% (p = 0.03, NNH 16)
 pruritus in 10.4% vs. 1.1% (p < 0.001, NNH 10)
 injury in 4.4% vs. 11.7% (p = 0.01, NNT 14)
 Reference - JAMA 2007 Oct 10;298(14):1641, editorial can be found in JAMA 2007 Oct
10;298(14):1691, commentary can be found in JAMA 2008 Jan 30;299(4):405
o topiramate may reduce alcohol use in patients with alcohol dependence (level 2
[mid-level] evidence)
 based on randomized trial with high dropout rate
 150 patients with alcohol dependence randomized to topiramate (25 mg daily titrated to
150 mg twice daily) vs. placebo for 12 weeks in addition to weekly standardized medication
compliance management
 only 103 patients (69%) completed the study, but intention-to-treat analysis included all
150 patients who completed at least 1 week of treatment
 at baseline, patients were drinking about 9 drinks per drinking day
 comparing topiramate vs. placebo at 12 weeks
 decrease in number of drinks per drinking day -6.2 vs. -3.1 (p = 0.0009)
 fewer heavy drinking days -60.3% vs. -32.7% (p = 0.0003)
 days abstinent 44.2% vs. 18% (p = 0.0003)
 Reference - Lancet 2003 May 17;361(9370):1677 EBSCOhost Full Text, editorial can
be found in Lancet 2003 May 17;361(9370):1666 EBSCOhost Full Text, commentary
can be found in J Fam Pract 2003 Sep;52(9):682 EBSCOhost Full Text, Am Fam
Physician 2004 Jan 1;69(1):195, Evidence-Based Medicine 2004 Jan-Feb;9(1):24
o topiramate may improve quality of life measures (level 2 [mid-level] evidence)
 based on above 2 randomized trials with high dropout rates
 371 adults with alcohol dependence randomized to topiramate vs. placebo for 14 weeks
 only 256 (69%) of patients completed trial
 significant improvements with topiramate (compared to placebo) in
 reducing body mass
 obsessional thoughts and compulsions about alcohol
 increased psychosocial well-being
 some aspects of quality of life
 all liver enzyme levels
 plasma cholesterol levels
 blood pressure
 Reference - Arch Intern Med 2008 Jun 9;168(11):1188 full-text
 150 persons with alcohol dependence randomized to topiramate vs. placebo for 12 weeks
 significant improvements with topiramate in overall well-being, life satisfaction and
medical consequences of drinking compared to placebo
 only 103 (69%) patients completed trial
 Reference - Arch Gen Psychiatry 2004 Sep;61(9):905 full-text, summary can be found
in Am Fam Physician 2005 Aug 1;72(3):510
Valproate:
 valproate may reduce heavy drinking in adult outpatients with alcohol use disorder (level
2 [mid-level] evidence)
o based on systematic review with study-specific quality measures not reported
o systematic review of 122 randomized trials and 1 cohort study evaluating pharmacotherapies for
alcohol use disorder in 22,803 adult outpatients
o trials had treatment duration range of 12-52 weeks
o most trials enrolled patients following detoxification or required sobriety period ≥ 3 days
o most trials included psychosocial co-interventions
o 2 trials with 81 patients compared valproate to placebo, including 1 trial of patients with
comorbid bipolar disorder summarized below
 o in analysis of 2 trials with 81 patients comparing valproate to placebo, valproate associated with
decreased risk of return to heavy drinking (risk difference -0.32, 95% CI -0.11 to -0.52)
o Reference - JAMA 2014 May 14;311(18):1889 full-text, editorial can be found in JAMA
2014;311(18):1861 , commentary can be found in Ann Intern Med 2014 Oct 21;161(8):JC7, Evid
Based Ment Health 2015 Feb;18(1):16, Evid Based Ment Health 2015 Feb;18(1):16, J Fam Pract
2015 Apr;64(4):238 EBSCOhost Full Text, JAMA 2014 Oct 1;312(13):1349
o valproate may reduce heavy drinking at 24 weeks in patients with bipolar I disorder
and alcohol dependence (level 2 [mid-level] evidence)
 based on small randomized trial
 59 patients with alcohol dependence and acute episode of bipolar I disorder randomized to
valproate (divalproex sodium started at 750 mg/day and titrated to serum level 50-100
mcg/mL) vs. placebo for 24 weeks
 patients continued to receive usual treatment including lithium and psychosocial
interventions
 52 patients analyzed
 comparing valproate vs. placebo
 heavy drinking days in 44% vs. 68% (no p value reported)
 proportion of days reported as heavy drinking days 9% vs. 19% of days (p = 0.02)
 mean number of drinks per heavy drinking day 5.6 vs. 10.2 (p = 0.02)
 mean number of drinks per drinking day (5.1 vs. 8.9 drinks, (p = 0.02)
 median time to relapse of sustained heavy drinking 93 vs. 62 days (p = 0.048)
 no significant differences between valproate and placebo in improvements of mania and
depression
 Reference - Arch Gen Psychiatry 2005 Jan;62(1):37 full-text
Comparative efficacy and combination therapies:
 comparisons and combinations of acamprosate and naltrexone
o acamprosate and naltrexone similarly reduce risk for drinking after detoxification in
alcohol dependent patients (level 1 [likely reliable] evidence), but evidence for
combination therapy is conflicting
 based on 2 systematic reviews
 Cochrane review of 24 randomized trials evaluating acamprosate in 6,894 alcohol-dependent
patients after completing detoxification
 patients mostly men (median age 42 years)
 study drugs were acamprosate in 2,563 patients, placebo in 2,929 patients
and naltrexone in 402 patients
 3 trials compared acamprosate vs. naltrexone (COMBINE study provided 76.5% of the
patients for this comparison)
 no significant differences in
 return to any drinking in analysis of 3 trials with 800 patients
 percent of days abstinent in analysis of 2 trials with 720 patients, possibly
limited by heterogeneity
 return to heavy drinking in analysis of 3 trials with 800 patients
 acamprosate associated with higher risk of diarrhea (p < 0.0001)
 naltrexone associated with higher risk of nausea (p = 0.003), fatigue (p = 0.03),
and somnolence (p = 0.013)
 2 trials compared combination of acamprosate plus naltrexone vs. placebo (COMBINE
study provided 88.5% of the patients for this comparison)
 no significant differences in
 return to any drinking (and also heavy drinking) in analysis of 2 trials with 694
patients, but complete heterogeneity with COMBINE trial finding no significant
effect and smaller trial (with 80 patients in this comparison) finding large risk
reduction
 percent of days abstinent in 1 trials with 614 patients
 adverse effects significantly more common with combination therapy included
diarrhea, decreased appetite, nausea and vomiting
 2 trials compared combination of acamprosate plus naltrexone vs. acamprosate
(COMBINE study provided 88.5% of the patients for this comparison)
 no significant differences in
  return to any drinking (and also heavy drinking) in analysis of 2 trials with 688
patients, but heterogeneity with COMBINE study finding no significant effect
and smaller trial (with 80 patients in this comparison) finding large risk
reduction
 percent of days abstinent in 1 trials with 608 patients
 adverse effects significantly more common with combination therapy included
nausea and vomiting
 Reference - Cochrane Database Syst Rev 2010 Sep 8;(9):CD004332
 systematic review of 122 randomized trials and 1 cohort study evaluating pharmacotherapies
for alcohol use disorder in 22,803 adult outpatients
 all trials had treatment duration 12-52 weeks
 most trials enrolled patients following detoxification or required sobriety period ≥ 3 days
 most trials included psychosocial co-interventions
 4 trials compared acamprosate vs. naltrexone (including 2 high-quality trials summarized
below)
 comparing acamprosate to naltrexone, no significant differences in
 return to any drinking in analysis of 3 trials with 800 patients
 return to heavy drinking in analysis of 4 trials with 1,141 patients
 number of drinking days in analysis of 2 trials with 720 patients
 Reference - JAMA 2014;311(18):1889, editorial can be found in JAMA
2014;311(18):1861
o naltrexone and combined behavioral intervention are each modestly effective for
reducing risk for drinking, with no greater efficacy for combination therapy, and
acamprosate is ineffective (level 1 [likely reliable] evidence)
 based on randomized trial
 1,383 patients (median age 44 years) with primary alcohol dependence and very recent
alcohol abstinence (minimum 4 days abstinent) were randomized to 1 of 9 groups for 16
weeks
 naltrexone 100 mg daily (initially 25 mg for 4 days and 50 mg for 3 days) and medical
management
 acamprosate 1,000 mg 3 times daily and medical management
 naltrexone 100 mg daily and acamprosate 3 g/day and medical management
 placebo and medical management
 naltrexone 100 mg daily and combined behavioral intervention (up to 20 sessions lasting
50 minutes integrating aspects of cognitive behavioral therapy, 12-step facilitation,
motivational interviewing and support system involvement) and medical management
 acamprosate 3 g/day and combined behavioral intervention and medical management
 naltrexone 100 mg daily and acamprosate 3 g/day and combined behavioral intervention
and medical management
 placebo and combined behavioral intervention and medical management
 combined behavioral intervention with no pills and no medical management
 medical management (in 8 of the 9 groups) consisted of 9 office visits over 16 weeks
 outcomes at 16 weeks
 percent days abstinent
 higher with naltrexone (80.6%) than placebo (75.1%) in patients not receiving
combined behavioral intervention (effect size 0.22, 95% CI 0.03-0.4)
 higher with combined behavioral intervention (79.2%) than without (75.1%) in
patients receiving placebo (effect size 0.17, 95% CI -0.02 to 0.35)
 combination naltrexone plus combined behavioral intervention (77.1%) did not
further improve outcomes over either monotherapy
 acamprosate had no significant effect
 combined behavioral intervention with no pills had only 66.6% days abstinent
 naltrexone reduced proportion of patients with any heavy drinking (defined as ≥ 5
standard drinks/day for men or ≥ 4 or more standard drinks/day for women) (68.2% vs.
71.4%, p = 0.02, NNT 32)
 significant adverse effects with naltrexone compared to placebo were vomiting (15% vs.
9%, NNH 16), somnolence (37% vs. 24%, NNH 7), and aspartate aminotransferase
(AST) or alanine aminotransferase (ALT) 5 times upper normal limit (2% vs. 0, NNH 50)
  significant adverse effects with acamprosate compared to placebo were diarrhea (65%
vs. 35%, NNH 3), somnolence (31% vs. 24%, NNH 14) and alcohol detoxification (4%
vs. 1%, NNH 33)
 80%-87% of patients in each group had follow-up at 1 year
 combined behavioral intervention associated with trend (p = 0.08) toward higher
percent days abstinent compared to medical management, regardless of prescribed
medication
 naltrexone associated with lower risk of any return to heavy drinking (p = 0.04)
 no other significant differences
 Reference - COMBINE study (JAMA 2006 May 3;295(17):2003 full-text), editorial can be
found in JAMA 2006 May 3;295(17):2075, commentary can be found in Am Fam Physician
2006 Sep 1;74(5):828, JAMA 2006 Oct 11;296(14):1727 and in Evid Based Med 2007
Feb;12(1):20
 DynaMed commentary -- control group without medical management and without pills had
worst outcomes, suggesting medical management has efficacy although this was not a
primary focus of this study
 mu-opioid receptor (OPRM1) genotyping might predict naltrexone response, based on
analysis of 604 patients from this trial (Arch Gen Psychiatry 2008 Feb;65(2):135 full-text)
 cost-effectiveness analysis of COMBINE study can be found in Arch Gen Psychiatry 2008
Oct;65(10):1214 full-text
o naltrexone and acamprosate each reduce relapse rates following alcohol
detoxification, combination therapy is more effective than acamprosate alone (level 1
[likely reliable] evidence)
 based on randomized trial
 160 patients aged 18-65 years with alcoholism following detoxification (complete abstinence
for 12-15 days and negative drug screening) were randomized to naltrexone 50 mg once
daily vs. acamprosate 666 mg 3 times daily vs. combination vs. placebo for 12 weeks
 75 patients completed full course of treatment
 relapse defined as 5 or more drinks/day (4 or more for women) or at least 5 drinking
days/week
 overall relapse rate 42.5%
 relapse rates
 22.5% with combination therapy
 30% with naltrexone
 42.5% with acamprosate
 75% with placebo
 combination had significantly lower relapse rates compared to placebo (p = 0.008) or
acamprosate alone (p = 0.04), but comparison with naltrexone was not statistically
significant
 naltrexone had trend toward longer time to first drink and time to relapse compared to
acamprosate
 similar results reported in analysis of time to first drink
 Reference - Arch Gen Psychiatry 2003 Jan;60(1):92 full-text, summary can be found in Am
Fam Physician 2003 Jun 15;67(12):2592
 combination of sertraline plus naltrexone may increase abstinence rate and decrease
depression symptoms compared to either sertraline or naltrexone alone for patients with
depression and alcohol dependence (level 2 [mid-level] evidence)
o based on randomized trial with high dropout rate
o 170 patients with depression and alcohol dependence receiving cognitive-behavioral therapy
(CBT) randomized to 1 of 4 treatments for 14 weeks
 sertraline 200 mg/day
 naltrexone 100 mg/day
 combination sertraline plus naltrexone
 double placebo
o 43% did not complete trial
Combination
Outcomes Therapy Naltrexone Sertraline Placebo p value*
 Combination
Outcomes Therapy Naltrexone Sertraline Placebo p value*
Mean days to relapse to heavy
drinking 63.6 days 45.2 days 39.9 days 41.7 days p = 0.003

Patients totally abstinent during

treatment 53.7% 21.3% 27.5% 23.1% p = 0.001

Patients not meeting depressive

criteria at trial end 83.3% 68.8% 48.1% 56% p = 0.014

* p value for comparison of combination therapy vs. other 3 groups combined, p ≤ 0.01 required for statistical
significance after correction for multiple comparisons.
Results:
o Reference - Am J Psychiatry 2010 Jun;167(6):668 full-text, editorial can be found in Am J
Psychiatry 2010 Jun;167(6):620, commentary can be found in Curr Psychiatry Rep 2011
Aug;13(4):245
 addition of gabapentin to naltrexone may increase time to relapse and decrease drinks
per drinking day in initial 6 weeks of drinking cessation program (level 2 [mid-level]
evidence) but no data regarding use of gabapentin beyond 6 weeks
o based on randomized trial with allocation concealment not stated
o 150 patients with alcohol dependence (mean 12-13 drinks per drinking day) beginning cessation
program randomized to 1 of 3 treatments for 16 weeks
 naltrexone 50 mg/day plus gabapentin up to 1,200 mg/day for first 6 weeks
 naltrexone 50 mg/day plus placebo for first 6 weeks
 double placebo
o patients also received medical management and up to 16 combined behavioral therapy sessions
o 35% did not complete treatment but included in analysis
o 82%-88% patients provided drinking data for all 16 weeks
o comparing naltrexone-gabapentin vs. naltrexone alone at 6 weeks
 estimated likelihood of no return to heavy drinking 64% vs. 50% (NNT 8)
 longer time to relapse (p = 0.04)
 percent of heavy drinking days 4% vs. 14% (p < 0.001)
 number of drinks per drinking day 4 vs. 5.5 (p = 0.02)
 fewer positive gamma-glutamyltransferase (p = 0.02)
 better sleep reports (p = 0.03)
o comparing naltrexone-gabapentin vs. placebo at 6 weeks
 estimated likelihood of no return to heavy drinking 64% vs. 52% (NNT 9)
 longer time to relapse (not significant)
 percent of heavy drinking days 4% vs. 8% (not significant)
 number of drinks per drinking day 4 vs. 5.5 (p = 0.01)
 fewer positive gamma-glutamyltransferase (p = 0.02)
 better sleep reports (p = 0.02)
o differences no longer significant after gabapentin discontinuation
o naltrexone alone was not superior to placebo, consistent with findings in COMBINE study finding
naltrexone and combined behavioral treatment to each be effective but not additively effective
when combined
o naltrexone-gabapentin associated with significantly higher risk of daytime somnolence, blurred
vision and premature ejaculation
o Reference - Am J Psychiatry 2011 Jul;168(7):709 full-text
Other medications:
 baclofen (Lioresal)
o baclofen may be effective for maintaining alcohol abstinence in patients
with alcoholic cirrhosis (level 2 [mid-level] evidence)
 based on randomized trial with high dropout rate and differential loss to follow-up
  84 alcohol-dependent patients (mean age 56 years) with liver cirrhosis (mean Child-Pugh
score 9) randomized to baclofen (5 mg 3 times daily for 3 days then 10 mg 3 times daily) vs.
placebo for 12 weeks
 dropout rate 14% with baclofen vs. 31% with placebo (p = 0.12)
 alcohol abstinence in 71% with baclofen vs.29% with placebo (p = 0.0001, NNT 3)
 improvement in laboratory markers of liver disease observed with baclofen
 Reference - Lancet 2007 Dec 8;370(9603):1915, editorial can be found in Lancet 2007 Dec
8;370(9603):1884
o baclofen may reduce alcohol craving and intake (level 2 [mid-level] evidence)
 based on small randomized trial
 39 alcohol-dependent patients abstained from alcohol for 12-24 hours and were than
randomized to baclofen (5 mg 3 times daily for 3 days then 10 mg 3 times daily) vs. placebo
for 30 days
 baclofen associated with higher percentage of patients with complete abstinence and higher
number of cumulative abstinence days, reduced alcohol use and reduced obsessive-
compulsive cravings
 Reference - Alcohol Alcohol 2002 Sep-Oct;37(5):504
 ondansetron (Zofran) may be effective in reducing drinking in early-onset alcoholics
(level 2 [mid-level] evidence)
o based on randomized trial without intention-to-treat analysis
o 271 patients aged 25-65 years with alcoholism (DSM-III-R criteria) randomized to 1 of 4 regimens
orally twice a day for 11 weeks
 ondansetron 1 mcg/kg
 ondansetron 4 mcg/kg
 ondansetron 16 mcg/kg
 placebo
o outcomes analyzed in early-onset alcoholism (onset < 25 years old) and later onset groups
o all patients had weekly group cognitive behavioral therapy
o comparing outcomes in early-onset patients (actual number analyzed not reported)
Dosage Drinks/Day Drinks/Drinking Day
Ondansetron 1 mcg/kg 1.89* 4.75*

Ondansetron 4 mcg/kg 1.56* 4.28*

Ondansetron 16 mcg/kg 1.87* 5.18*

Placebo 3.30 6.90

Drinking Behavior Reported in Patients with Early-Onset Alcoholism (Onset < 25 Years Old):
o ondansetron 4 mcg/kg twice a day superior to placebo in increasing percentage of days abstinent
(70% vs. 50%, p = 0.02) and total days abstinent per study week (6.74 vs. 5.92, p = 0.03)
o results supported by differences in plasma carbohydrate deficient transferrin (CDT) level as an
objective marker for transient alcohol consumption
o among patients with late-onset alcoholism (onset after age 25), only significant difference was for
improved drinking outcomes in 16 mcg/kg twice daily group
o adverse effects included constipation 5%, headache 3.4%, rash or pruritus 2.2%
o Reference - JAMA 2000 Aug 23-30;284(8):963 full-text
 nalmefene may reduce drinking in adult outpatients with alcohol use disorder but with
increased risk for withdrawal (level 2 [mid-level] evidence)
o based on systematic review with study-specific quality measures not reported
o systematic review of 122 randomized trials and 1 cohort study evaluating pharmacotherapies for
alcohol use disorder in 22,803 adult outpatients
o all trials had treatment duration 12-52 weeks
o most trials enrolled patients following detoxification or required sobriety period ≥ 3 days
o most trials included psychosocial co-interventions
o 7 trials compared nalmefene vs. placebo
o comparing nalmefene to placebo, nalmefene associated with significantly
 fewer drinking days in analysis of 2 trials with 508 patients
 fewer heavy drinking days per month in analysis of 2 trials with 1,234 patients
  fewer drinks per drinking day in analysis of 3 trials with 608 patients
 increased risk of withdrawal from trial due to adverse events in analysis of 5 trials with 2,054
patients
o Reference - JAMA 2014 May 14;311(18):1889, editorial can be found in JAMA 2014 May
14;311(18):1861
 rimonabant may not prevent relapse to alcohol use (level 2 [mid-level] evidence)
o based on randomized trial with high dropout rate
o 260 detoxified alcohol-dependent patients randomized to rimonabant 10 mg twice daily vs.
placebo for 12 weeks
o comparing rimonabant vs. placebo
 complete treatment in 71.8% vs. 62.2%
 relapse to drinking occurred in 41.5% vs. 47.7% (not significant)
o Reference - J Clin Psychopharmacol 2008 Jun;28(3):317
 kudzu extract appears ineffective in preventing relapse in alcohol dependent patients
(level 2 [mid-level] evidence)
o based on small randomized trial with high dropout rate
o 38 veterans in substance abuse program randomized to kudzu vs. control for 4 months
o no significant differences between groups in relapse rates
o adverse effects included headache, dry mouth and anxiety
o Reference - J Altern Complement Med 2000 Feb;6(1):45 EBSCOhost Full Text
 pharmacologic treatments for anxiety have limited evidence to evaluate effect on alcohol
use in patients with anxiety and comorbid alcohol use disorders
o based on Cochrane review
o systematic review of 5 randomized trials evaluating pharmacologic treatments for anxiety in 290
patients with anxiety and comorbid alcohol use disorders
o anxiety disorders included posttraumatic stress disorder (PTSD) (2 trials), social anxiety disorder
(2 trials), and generalized anxiety disorder (1 trial)
o comparing paroxetine to placebo in patients with social anxiety disorder
 paroxetine associated with nonsignificant decrease in drinks per drinking day (mean
difference -2.42 drinks per drinking day, 95% CI -4.97 to 0.14 drinks per drinking day) in
analysis of 2 trials with 54 patients
 no significant difference in days abstinent in analysis of 2 trials with 54 patients, results
limited by significant heterogeneity
o no significant difference in drinking days or drinks per day comparing sertraline vs. placebo in 1
trial with 94 patients with PTSD
o comparing paroxetine vs. desipramine for 12 weeks in 1 trial with 44 patients with PTSD
 mean drinking days 13.7 days vs. 2.5 days (p < 0.05)
 mean drinks per drinking day 6.34 vs. 2.72 (not significant)
o Reference - Cochrane Database Syst Rev 2015 Jan 20;(1):CD007505
 review of gamma-hydroxybutyric acid for alcohol dependence can be found in Int J Environ Res Public
Health 2009 Jun;6(6):1917 full-text
Preoperative alcohol cessation:
 alcohol cessation for ≥ 1 month preoperatively may reduce postoperative morbidity in
patients with alcohol use disorder having elective surgery (level 2 [mid-level] evidence)
o based on Cochrane review of trials without blinding of outcome assessors
o systematic review of 2 randomized trials comparing preoperative alcohol cessation interventions
vs. standard care in 69 patients with alcohol use disorder having elective surgery
o interventions included
 disulfiram for 1 month prior to surgery
 disulfiram plus motivational counseling and chlordiazepoxide (for withdrawal symptoms) for 3
months prior to surgery
o comparing preoperative alcohol cessation to standard care in analysis of 2 trials with 69 patients
 preoperative alcohol cessation associated with decreased postoperative complications
 odds ratio 0.22 (95% CI 0.08-0.61)
 NNT 2-9 with postoperative complications in 62% of standard care group
 no significant differences in
 in-hospital or 30-day mortality
  length of hospital stay
o details of largest trial included below
o Reference - Cochrane Database Syst Rev 2012 Jul 11;(7):CD008343
o alcohol abstinence for 1 month preoperatively reduces postoperative morbidity in
patients with alcohol use disorder (level 2 [mid-level] evidence)
 based on randomized trial without blinding
 42 patients with alcohol use disorder without liver disease admitted for elective colorectal
surgery randomized to withdrawal from alcohol consumption for 1 month before operation
(disulfiram-controlled) vs. continuous drinking
 comparing withdrawal vs. continuous drinking
 postoperative complications in 31% vs. 74% (p = 0.02, NNT 3)
 23% vs. 85% postoperative myocardial ischemia on second postoperative day (NNT 1.6)
 33% vs. 86% arrhythmias on second postoperative day (NNT 2)
 Reference - BMJ 1999 May 15;318(7194):1311, commentary can be found in ACP J Club
1999 Sep-Oct;131(2):38
Other management:
 insufficient evidence to determine if most interventions for problem drinking might reduce
injuries
o based on Cochrane review of trials with inadequate power to detect significant differences
o systematic review of 23 randomized trials without allocation concealment examined multiple
interventions
o 17 trials provided results for relevant outcomes
o relative risk reductions ranged from 27% to 65% in favor of interventions but only 1 study of
alcohol-related injuries reached statistical significance
o reported alcohol-related injuries in 21% of adolescents receiving brief intervention in emergency
department vs. 50% in control group at 6 month followup in randomized trial of 94 patients (odds
ratio 0.25, 95% CI 0.09-0.69)
o trials may have had insufficient power to detect significant differences in injury rates
o interventions reviewed include
 counselling or structured therapy in 9 trials
 brief intervention in 7 trials
 education in 3 trials
 metronidazole or chlordiazepoxide in 1 trial
 acupuncture in 1 trial
 education of patient's partner in 1 trial
 Alcoholics Anonymous meetings in 1 trial
 telephone based aftercare in 1 trial
o Reference - Cochrane Database Syst Rev 2004;(3):CD001857
 insufficient evidence regarding effectiveness of 12-step programs
o based on Cochrane review
o systematic review of 8 trials of Alcoholics Anonymous (AA) or other 12-step facilitation programs
with 3,417 adults with alcohol dependence
o AA may help patients accept treatment and stay in treatment, based on 1 small trial which
combined AA with other interventions
o few differences in amount of drinks and percentage of drinking days found in 3 trials of AA plus
other interventions
o severity of addiction and drinking consequence not significantly influenced by other 12-step
facilitation approaches
o Reference - Cochrane Database Syst Rev 2006 Jul 19;(3):CD005032
o DynaMed commentary -- control groups had other treatments, so this review does not provide
evidence comparing 12-step programs to no support
 Alcoholics Anonymous (AA) attendance may reduce alcohol consumption and depressive
symptoms (level 2 [mid-level] evidence)
o based on secondary analyses of Project MATCH study
o in Project MATCH study 1,726 patients with alcohol dependence were randomized to 12-step
facilitation vs. cognitive-behavioral therapy vs. motivational enhancement therapy
 o no significant differences in alcohol use outcomes among groups in intention-to-treat analysis of
Project MATCH study
o in analysis of 1,706 participants followed for 15 months, greater Alcoholics Anonymous attendance
was associated with better subsequent alcohol use outcomes and decreased depression (Addiction
2010 Apr;105(4):626 EBSCOhost Full Text), editorial can be found in Addiction 2010
Apr;105(4):637 EBSCOhost Full Text
o Alcoholics Anonymous (AA) attendance may be associated with improved alcohol use outcomes in
subgroup for whom 12-step facilitation might determine if attendance occurs
 rationale is that many patients will choose to attend or not attend AA regardless of
intervention applied
 in Project MATCH AA attendance was higher with 12-step facilitation (34.7%) than other 2
groups (21.2%)
 propensity score matching used to identify subgroups presumed to be the 13.5% patients
who would attend AA under the 12-step facilitation intervention but not under the other
interventions
 AA attendance associated with improved drinking outcomes in this subgroup
 Reference - Drug Alcohol Depend 2013 Apr 1;129(1-2):54
 early intervention for post-traumatic stress disorder (PTSD) in patients with alcohol abuse
may decrease alcohol abuse at 1 year (level 2 [mid-level] evidence)
o based on cohort within a randomized trial
o 120 injured surgical inpatients at level 1 trauma center randomized to collaborative care vs. usual
care
o 36 of these patients had alcohol abuse/dependence
o collaborative care included continuous postinjury case management, motivational interviews
regarding alcohol abuse and dependence, and drugs and/or cognitive behavioral therapy for
patients with persistent PTSD at 3 months
o trend toward more patients with alcohol abuse/dependence enrolled in usual care
o collaborative care reduced PTSD symptoms and rate of alcohol abuse/dependence over 1 year
o change in rate of alcohol abuse/dependence over 1 year -24.2% with collaborative care vs. 12.9%
with usual care (p < 0.001)
o Reference - Arch Gen Psychiatry 2004 May;61(5):498 full-text, summary can be found in Am Fam
Physician 2005 Feb 15;71(4):798
 alcohol ignition interlock program may reduce drunk driving recidivism (level 2 [mid-
level] evidence)
o based on Cochrane review of trial with methodological limitations
o systematic review found 1 randomized trial with 1,387 participants, 10 controlled trials and 3
ongoing trials
o randomized trial judged to have some risk of selection bias because only individuals who
demonstrated treatment compliance for drinking problems were permitted to enter study
o while device was installed in vehicle relative risk of recidivism was 0.36 (95% CI 0.21-0.63)
o controlled trials had similar trend
o no trials had evidence that program had effectiveness after device removed
o Reference - Cochrane Database Syst Rev 2004 Oct 18;(4):CD004168 (review updated 2008 Sep 8)
 concomitant treatment of alcohol use and smoking
o smoking cessation interventions provided during treatment for other addictions
associated with increased likelihood of long-term abstinence from alcohol and illicit
drugs (level 2 [mid-level] evidence)
 based on meta-analysis of trials with methodological limitations
 systematic review and analysis of 19 randomized trials of smoking cessation interventions in
persons with current addictions in treatment or recovery
 studies evaluated either nicotine replacement therapy or counseling interventions
 only 3 studies provided description of randomization procedure
 studies without pharmacological intervention did not have allocation concealment stated
 abstinence with smoking cessation therapy 37% vs. 31% with control (relative risk 1.25, 95%
CI 1.07 - 1.46) at follow-up in 7 studies with 1,135 patients
 effects on smoking cessation were significant post-treatment but not at follow-up after at
least 6 months
 Reference - J Consult Clin Psychol 2004 Dec;72(6):1144
 o addition of brief alcohol intervention with smoking cessation program may decrease
alcohol consumption for heavy drinkers seeking smoking cessation (level 2 [mid-level]
evidence)
 based on quasi-randomized trial
 119 patients seeking smoking cessation with history of heavy drinking given 8 weeks of
nicotine replacement therapy and randomized to 4 session standard smoking cessation
program vs. standard cessation program incorporated with brief alcohol intervention followed
for 26 weeks
 standard plus alcohol intervention group consumed 20% fewer drinks per week (p < 0.027)
 Reference - J Consult Clin Psychol 2008 Oct;76(5):852
 community reinforcement and family training (CRAFT) teaching behavioral change skills
to concerned significant others may increase treatment uptake by unmotivated problem
drinkers (level 3 [lacking direct] evidence)
o based on randomized trial without clinical outcomes
o 130 concerned significant others of unmotivated problem drinkers randomized to 1 of 3 manual-
guided approaches with 12 hours of contact
 Al-Anon facilitation therapy designed to encourage involvement in 12-step program
 Johnson Institute intervention to prepare for confrontational family meeting
 CRAFT approach teaching behavior change skills to use at home
o 94% completed follow-up interviews over 12 months
o engagement of initially unmotivated problem drinkers in treatment was 13% with Al-Anon, 30%
with Johnson Institute and 64% with CRAFT interventions; treatment engagement typically
occurred after 4-6 sessions
o no significant differences between groups in improvements in concerned significant other
functioning and relationship quality
o no clinical outcomes reported
o Reference - J Consult Clin Psychol 1999 Oct;67(5):688
 therapeutic communities may be beneficial for drug users but evidence limited (level 2
[mid-level] evidence)
o based on Cochrane review of trials with multiple methodologic limitations
o systematic review of 7 randomized trials of therapeutic communities for rehabilitation of drug
users
o no trial reported adequate allocation concealment, randomization method unclear or compromised
in 5 trials, most trials did not conduct intention-to-treat analyses
o compared with community residence in 1 trial, no significant differences for treatment completion
o comparing residential versus day therapeutic communities in 1 trial, residential therapeutic
communities associated with significantly lower attrition in first 2 weeks but significantly lower
abstinence rates at 6 months
o comparing standard versus enhanced abbreviated therapeutic communities in 1 trial, standard
therapeutic communities had higher number of employed participants
o comparing 3-month vs. 6-month program within modified therapeutic communities in 1 trial,
completion rate higher with 3-month program
o comparing 6-month vs. 12-month program within modified therapeutic communities in 1 trial,
retention rate at 40 days higher with 12-month program
o comparing therapeutic communities with no treatment within prison setting in 1 trial, therapeutic
communities associated with fewer re-incarcerations at 12 months after release from prison
o comparing therapeutic communities with mental health treatment programs within prison setting
in 1 trial, therapeutic communities associated with fewer re-incarcerations, criminal activity, and
alcohol and drug offenses at 12 months after release from prison
o Reference - Cochrane Database Syst Rev 2006 Jan 25;(1):CD005338
 day hospital and residential addiction treatment programs appear to have similar
abstinence rates for drug or alcohol dependency at 12 months (level 2 [mid-level]
evidence)
o based on quasi-randomized trial
o 733 patients (mean age 41 years) with drug or alcohol dependency seeking care were assigned to
1 of 4 treatment groups and followed for 12 months
 day hospital treatment (random assignment)
 community residential treatment (random assignment)
  self directed hospital treatment
 directed to community residential treatment because of high environmental risk
o 95% of patients analyzed
o > 50% of patients achieved 30-day abstinence at follow-up (not significant between groups)
o length of stay at initial treatment program and 12-step attendance were associated with
abstinence (p < 0.001)
o Reference - J Consult Clin Psychol 2007 Dec;75(6):947
 case management may enhance linkage with other treatment services in patients with
substance use disorders but may not reduce illicit drug use (level 2 [mid-level] evidence)
o based on withdrawn Cochrane review with clinical and statistical heterogeneity
o systematic review of 15 randomized trials comparing a specific model of case management vs.
usual care or another treatment model in patients with at least 1 alcohol- or drug-related problem
o no significant effect for outcome of illicit drug use in 7 trials with 2,391 patients, analysis limited
by heterogeneity
o case management associated with positive effect on linkage to other treatment services in 10
trials with 3,132 patients (p < 0.001), but results may be limited by heterogeneity
o case management superior to psychoeducation and drug counseling for reducing drug use in 1
trial
o Reference - Cochrane Database Syst Rev 2007 Oct 17;(4):CD006265 (review updated 2011 Sep 6)
o DynaMed commentary -- review withdrawn 2014 Apr 15 because out of date and authors
currently not available to update
 chronic care management intervention may not increase abstinence compared to usual
primary care in patients with dependence on alcohol or other drugs (level 2 [mid-level]
evidence)
o based on randomized trial with low compliance
o 563 adults with alcohol and/or other drug dependence randomized to 1 of 2 interventions and
followed for 1 year
 chronic care management consisting of motivational enhancement therapy for 4 sessions,
relapse prevention counseling, on-site medical, addiction, and psychiatric treatment, social
work assistance, and referrals to specialty addiction and mutual help groups
 usual primary care with single appointment plus information about treatment resources and
telephone number to arrange counseling (control)
o 73% had alcohol dependence and 83% had drug dependence (including cocaine in 60%)
o 27% in chronic care management group completed all 4 motivational enhancement therapy
sessions
o 95% completed follow-up and 98% were included in modified intention-to-treat analyses
o self-reported 30-day abstinence from heavy drinking, opioids, and stimulants in 44% in chronic
care management group vs. 42% in control group (not significant)
o no significant differences in
 alcohol or drug addiction severity, health-related quality of life, or hospitalization or
emergency department stays
 self-reported abstinence from heavy drinking or opioids and stimulants in subgroup analyses
o Reference - AHEAD trial (JAMA 2013 Sep 18;310(11):1156), editorial can be found in JAMA 2013
Sep 18;310(11):1132
 acupuncture does not appear useful for treatment of alcohol dependence (Alternative Medicine Alert
2002 Apr;5(4):42)
 transcranial magnetic stimulation might decrease alcohol craving in men but not
associated with decrease in relapse (level 2 [mid-level] evidence)
o based on small randomized trial with outcome assessors not blinded
o 45 male patients with alcohol dependence syndrome randomized to repetitive transcranial
magnetic stimulation vs. sham stimulation for 10 sessions
o 73.4%-76.7% given anti-craving medication after sessions as determined by treating team
o active treatment associated with decrease in alcohol craving scores (p < 0.0005)
o relapse in 13.8% with active vs. 33.3% with sham stimulation (not significant)
o no pain reported during sham transcranial magnetic stimulation
o Reference - Addiction 2010 Jan;105(1):49 EBSCOhost Full Text
 no studies found evaluating managed alcohol programs for alcohol addiction in adults
with high risk of substance abuse
 o based on Cochrane review
o Reference - Cochrane Database Syst Rev 2012 Dec 12;(12):CD006747
Follow-up:
 continuing care via mobile phone application might reduce risky drinking and increase
abstinence after completion of treatment for alcohol dependence (level 2 [mid-level]
evidence)
o based on randomized trial without blinding
o 349 adults completing residential treatment for alcohol dependence were randomized to
continuing care intervention for 8 months after discharge and followed to 12 months vs. no
intervention
 patients in intervention group received mobile phone with application providing monitoring,
information, communication, and support services to patients including ways to stay in
contact with counselors
 all patients received treatment as usual for 1 year after discharge, which did not include
coordinated continuing care
o risky drinking defined as > 4 drinks for men and > 3 drinks for women over 2-hour period
o comparing continuing care intervention vs. no intervention
 mean number of risky drinking days in previous month 1.39 days vs. 2.75 days (p = 0.003)
 abstinence in 52% vs. 40% (p = 0.032, NNT 9)
o Reference - JAMA Psychiatry 2014 May;71(5):566 full-text
 outpatient aftercare may improve outcomes in adolescents with alcohol use disorders
(level 2 [mid-level] evidence)
o based on randomized trial with allocation concealment not stated
o 144 patients aged 13-18 years with alcohol use disorders randomized to 1 of 3 treatments
 aftercare consisting of 5 in-person, therapy sessions
 aftercare consisting of 5 brief telephone sessions
 no active aftercare
o all patients received nine weekly outpatient cognitive behavioral therapy group sessions before
randomization
o patients enrolled in aftercare showed significantly fewer drinking days (p = 0.044) and fewer
heavy drinking days (p = 0.035) per month compared patients with no active aftercare
o Reference - J Am Acad Child Adolesc Psychiatry 2008 Dec;47(12):1405
 telephone-based continuing care appears effective for step-down treatment after
stabilization treatment for alcohol and cocaine dependence (level 2 [mid-level] evidence)
o based on randomized trial with allocation concealment not stated
o 359 patients with alcohol and/or cocaine dependence randomized to one of following
 telephone-based care (weekly supportive group sessions for 4 weeks plus weekly telephone-
based brief counseling contacts for 12 weeks)
 cognitive behavioral relapse prevention (twice weekly for 12 weeks)
 standard group counseling (twice weekly for 12 weeks)
o analysis not adjusted for multiple interim assessments
o comparing telephone-based care vs. cognitive behavioral relapse prevention vs. standard group
counseling
 no significant difference in mean percentage of days abstinent comparing telephone-based
care vs. cognitive behavioral relapse prevention vs. standard group counseling over 2 years
 telephone-based care more effective at reducing rates of total abstinence (p < 0.05)
 telephone-based care less effective in subgroup of high-risk patients with alcohol and cocaine
codependence who had poor progress achieving intensive outpatient program goals
o effectiveness assessed every 3 months but the only time frame when efficacy seen was from 21-
24 months
o Reference - Arch Gen Psychiatry 2005 Feb;62(2):199 full-text
Complications and Prognosis
Complications:
 alcohol use disorder contributes significantly to mortality
o 3.8% global deaths in 2004 attributable to alcohol
 among alcohol-related deaths
 26.8% caused by unintentional injury
  22% by cardiovascular diseases
 19.6% by cancer
 15% by cirrhosis of the liver
 4.6% global disability-adjusted life-years attributable to alcohol
 Reference - Lancet 2009 Jun 27;373(9682):2223
o alcohol associated with violent deaths in United States
 based on 2007 National Violent Death Reporting System
 16,319 deaths reported from 16 states
 73.8% decedents tested for alcohol
 33.4% of those tested were positive for alcohol
 59.1% of those testing positive had blood alcohol level > 0.08 g/dL (legal limit in most states)
 Reference - MMWR Surveill Summ 2010 May 14;59(4):1 EBSCOhost Full Text full-text
o alcohol use disorder associated with increased all-cause mortality in United States
veterans
 based on a prospective cohort study
 559,985 respondents to 1999 Large Health Survey of Veteran Enrollees
 131,396 (27%)veterans died during 9-year follow-up
 increased risk of all-cause mortality associated (after adjusted for age, race, gender,
psychiatric and medical comorbidity, obesity, current smoking and exercise frequency) with
 alcohol use disorder (hazard ratio [HR] 1.33, 95% CI 1.29-1.37)
 drug use disorder (HR 1.11, 95% CI 1.06-1.16)
 schizophrenia (HR 1.13, 95% CI 1.09-1.16)
 no significant association between all-cause mortality and posttraumatic stress disorder,
bipolar disorder, major depressive disorder or other depression after adjusting for psychiatric
and medical comorbidity, obesity, current smoking, and exercise frequency
 Reference - Psychosom Med 2010 Oct;72(8):817 full-text
o heavy drinking (> 22 units/week) associated with increased mortality, no clear
benefit from moderate drinking
 prospective cohort study at 27 workplaces in west of Scotland of 5,766 men aged 35-64
followed over 21 years
 risk for all cause mortality similar for nondrinkers and men drinking up to 14 units/week,
mortality risk then increased with increasing alcohol consumption
 increased mortality risk remained significant after adjustment for other risk factors for men
drinking 22 or more units/week
 no strong relation between alcohol consumption and mortality from coronary heart disease
after risk factor adjustment
 strong positive relation seen between alcohol consumption and risk of mortality from stroke
 Reference - BMJ 1999 Jun 26;318(7200):1725
 DynaMed commentary -- a United Kingdom "unit" of alcohol is 10 g, compared with 14 g for
"standard" drink in United States; for example, one United Kingdom unit is about 8 ounces of
beer
o moderate drinking in combination with heavy smoking associated with increased all-
cause mortality in men
 based on cohort of 64,515 men aged 30-89 years followed for up to 8 years in Shanghai,
China
 light to moderate drinking associated with lower cardiovascular mortality in never-smokers,
but not in former or current smokers
 heavy drinking (> 42 drinks/week) associated with higher all-cause and cancer mortality
 Reference - Prev Med 2007 Oct;45(4):313
o although alcohol use disorder is associated with increased mortality, light to moderate drinking
has been associated with lower risk of coronary heart disease in cohort studies in United States
and Denmark (J Am Geriatr Soc 2006 Jan;54(1):30 EBSCOhost Full Text, J Am Coll Cardiol
2010 Mar 30;55(13):1328, BMJ 2006 May 27;332(7552):1244)
o heavy alcohol use associated with increased cancer mortality
 based on systematic review of 18 cohort studies evaluating association between alcohol
consumption and cancer mortality
  compared with non/occasional drinking
 heavy drinking (≥ 50 g/day) associated with increased cancer mortality (relative risk
1.31, 95% CI 1.23-1.39)
 light drinking (≤ 12.5 g/day) associated with reduced cancer mortality (relative risk 0.91,
95% CI 0.89-0.94)
 Reference - Ann Oncol 2013 Mar;24(3):807
 heavy alcohol use associated with increased risk for pancreatitis and pancreatic cancer
o risk of alcoholic pancreatitis increases with increasing alcohol consumption, usually occurring after
> 5 years of heavy alcohol consumption > 50 grams/day (Lancet 2008 Jan 12;371(9607):143)
o increasing amount of alcohol intake associated with increased risk of acute
pancreatitis
 based on cohort study
 17,905 men and women in Copenhagen City Heart Study evaluated
 hazard ratios adjusted for age, sex, smoking, education, and body mass index
 compared to 0 drinks, increased risk for acute pancreatitis by alcohol intake
 35-48 drinks/week (adjusted hazard ratio [HR] 3.5, 95% CI 1.8-7.1)
 > 48 drinks/week (adjusted HR 3.3, 95% CI 1.5-7.3)
 hazard ratios comparing lower amounts of alcohol consumption to abstinence did not find
significant differences
 associations similar for men and women
 drinking frequency not independently associated with pancreatitis
 Reference - Am J Epidemiol 2008 Oct 15;168(8):932 full-text
o heavy alcohol use associated with increased risk of pancreatic cancer in men
 based on cohort study
 470,681 patients from the American Association of Retired persons (AARP) evaluated by
questionnaire
 exocrine pancreatic cancer developed in 1,149 patients at mean 7.3 years
 compared to light drinkers, risk for pancreatic cancer increased in men with
 ≥ 3 drinks/day (relative risk [RR] 1.5, 95% CI 1.18-1.9)
 ≥ 6 drinks/day (RR 1.7, 95% CI 1.2-2.38)
 heavy alcohol use not associated with significant increased risk for pancreatic cancer in
women
 Reference - Am J Epidemiol 2009 May 1;169(9):1043 full-text
o alcohol consumption > 50-80 g/day may increase risk for alcoholic pancreatitis, and
risk may increase with increasing drinking duration
 based on literature review
 no universally accepted criteria defines dose or duration cutoff for alcoholic pancreatitis, but
minimum consumption averages > 50-80 g/day with or without minimum drinking duration
 in general, patients with pancreatitis have history of heavy alcohol consumption
averaging 80-150 g/day for 10-15 years, but cases have been reported with shorter
drinking duration (minimum 6-12 years)
 in men, onset of alcoholic pancreatitis typically occurs in fourth decade of life following
heavy alcohol consumption averaging 150 g/day for 10-15 years
 other etiologic and genetic factors likely contribute to alcoholic pancreatitis as only a minority
of heavy drinkers will develop the disease (2%-5%)
 Reference - World J Gastroenterol 2013 Feb 7;19(5):638 full-text
o see Causes of acute pancreatitis for additional information
 excessive drinking associated with functional impairment in elderly
o cohort study of 161 persons > 60 years old who reported drinking at least once in previous 3
months
o drinking > 7 drinks/week or > 3 drinks/occasion was associated with impairments in self-reported
instrumental activities of daily living
o Reference - J Am Geriatr Soc 2003 Jan;51(1):44 EBSCOhost Full Text
 high alcohol consumption (more than 3 drinks/day or 21 drinks/week) associated with
obesity
 o alcohol intake > 30 g/day (heavy drinking) associated with weight gain and obesity in prospective
study of 7,608 men 40-59 years old, 6,832 completed 5-year follow-up (Am J Clin Nutr 2003
May;77(5):1312)
o alcohol consumption at least 21 units/week associated with higher measures of general adiposity
(body mass index, % body fat) and central adiposity (waist circumference, waist-to-hip ratio) in
cross-sectional study of 3,327 British men aged 60-79 years, irrespective of type of drink; 1 unit of
alcohol (drink) defined as half pint of beer, single measure of spirits or glass of wine (about 10 g
of alcohol) (Int J Obes (Lond) 2005 Dec;29(12):1436 EBSCOhost Full Text)
 complications of binge drinking
o binge drinking associated with increased mortality after acute myocardial infarction
 prospective inception cohort study of 1,919 patients hospitalized with myocardial infarction at
45 United States hospitals 1989-1994, median follow-up 3.8 years
 250 (13%) reported binge drinking defined as 3 or more drinks within 1-2 hours, 94% of
binge drinkers were men
 318 (16.6%) died during follow-up
 binge drinkers had hazard ratio for mortality of 2 (95% CI 1.3-3) compared with drinkers who
did not binge
 Reference - Circulation 2005 Dec 20;112(25):3839
o binge drinking associated with increased risk of stroke
 based on cohort of 15,965 Finnish men and women aged 25-64 years who participated in a
national risk factor survey and had no history of stroke at baseline followed for 10 years
 binge drinking was defined as consuming ≥ 6 drinks of the same alcoholic beverage in men
or ≥ 4 drinks in women in 1 session
 adjusted hazard ratio for total strokes among binge drinkers was 1.85 (95% CI 1.35-2.54)
compared with non-binge drinkers
 adjusted hazard ratio for ischemic strokes among binge drinkers was 1.99 (95% CI 1.39 to
2.87) compared with non-binge drinkers
 Reference - Stroke 2008 Dec;39(12):3179
o binge drinking in adolescence may be associated with adverse social and psychiatric
outcomes later in life
 based on cohort of 11,261 adolescents (age 16 at enrollment) followed for 30 years
 17.7% reported binge drinking in 2 weeks prior to enrollment
 binge drinking associated with increased risks for
 adult alcohol dependence
 excessive regular alcohol consumption
 illicit drug use
 psychiatric morbidity
 homelessness
 convictions
 school exclusion
 lack of qualifications
 accidents
 Reference - J Epidemiol Community Health 2007 Oct;61(10):902
 complications of alcoholism
o neonatal complications - fetal alcohol syndrome and a variety of more subtle effects
o neurologic complications - cerebellar degeneration, brain cell degeneration, peripheral
neuropathies, seizures
o alcohol use in middle age may be associated with increased risk for future dementia in
adults genetically predisposed to dementia
 based on retrospective cohort study
 1,464 men and women aged 65-79 years initially interviewed for alcohol intake in 1972 or
1977 and followed for average 23 years
 1,018 (70%) were reexamined in 1998
 among carriers of apolipoprotein e4 allele, any alcohol intake in midlife was associated with
increased risk of dementia with patients reported use several times a month having increased
risk compared to nondrinkers or persons drinking < once per month
  no significant association between alcohol use and dementia risk in noncarriers with persons
drinking < once per month having lowest risk
 Reference - BMJ 2004 Sep 4;329(7465):539 full-text
o hospital-treated alcohol intoxication in late adolescence associated with increased
risk of young-onset dementia in men
 based on retrospective cohort study
 488,484 Swedish males (mean age 18 years) conscripted for mandatory military service had
standardized cognitive and physical examinations and were followed for median 37 years
 487 men diagnosed with young-onset dementia (< 65 years old) at median age of 54 years
 hospital-treated alcohol intoxication associated with increased risk of young-onset dementia
(adjusted hazard ratio [HR] 4.82, 95% CI 3.83-6.05)
 Reference - JAMA Intern Med 2013 Sep 23;173(17):1612, correction can be found in JAMA
Intern Med 2013 Oct 14;173(18):1756, editorial can be found in JAMA Intern Med 2013 Sep
23;173(17):1619
o gastrointestinal complications - esophagitis, gastritis, esophageal varices, peptic ulcer disease,
impaired intestinal absorption
o hepatic complications - fatty liver, alcoholic hepatitis, alcoholic cirrhosis
o cardiac complications - cardiomyopathy, atrial flutter or atrial fibrillation ("holiday heart
syndrome")
 light to moderate drinking may reduce risk for myocardial infarction but heavier drinking does
not further reduce risk, see Dietary interventions for cardiovascular disease prevention
 heavy alcohol consumption may increase risk of atrial fibrillation in men
 alcohol consumption may have modest effect on risk of atrial fibrillation or
flutter in men
 prospective study of 47,949 Danish persons (mean age 56 years) followed for mean
5.7 years
 compared to lowest quintile of alcohol use, higher levels of alcohol use had
 1.04 to 1.46 times higher incidence of atrial fibrillation or flutter in men (p =
0.04)
 1.09 to 1.27 times higher incidence in women (p = 0.69)
 Reference - Arch Intern Med 2004 Oct 11;164(18):1993
 heavy alcohol consumption associated with increased risk of atrial fibrillation
 prospective cohort study of 16,415 men and women, 1,071 developed atrial
fibrillation during follow-up
 consumption of 35 or more drinks/week among men associated with atrial fibrillation
(hazard ratio 1.45, adjusted hazard ratio 1.63)
 few women consumed 35 or more drinks/week
 Reference - Circulation 2005 Sep 20;112(12):1736
 angiotensin-converting enzyme (ACE) genotype related to susceptibility to
cardiomyopathy in alcoholics
 based on case-control study comparing alcoholic men presenting to emergency
department with symptomatic heart failure, no apparent nonalcoholic causes and left
ventricular ejection fractions < 50% (cases) with controls from outpatient alcoholism
treatment who had similar alcohol consumption and left ventricular ejection fractions >
60%
 57% cases vs. 7% controls had homozygous ACE deletion allele (DD genotype), odds
ratio 16.4
 89% of subjects with DD genotype vs. 34% with II or ID genotype had cardiomyopathy
 Reference - Ann Intern Med 2002 Sep 3;137(5):321 in J Watch Online 2002 Sep 10
o skeletal myopathies
o hematologic complications - anemia, thrombocytopenia, impaired leukocyte function, hemolysis
o metabolic complications - hypoglycemia, hypokalemia, hypomagnesemia, hypocalcemia,
hypophosphatemia, hyperuricemia, hyperlipidemia
 case presentation of neurological complications of heavy alcohol use can be found in JAMA 2008 Mar
5;299(9):1046, commentary can be found in JAMA 2008 Jun 25;299(24):2853
 alcohol use and postoperative complications
o higher Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) score in year
before surgery associated with increased risk for postoperative complications
  based on retrospective cohort study
 9,176 male Veterans Affairs patients who had major noncardiac surgery and who completed
AUDIT-C alcohol screening questionnaire within 1 year before surgery were evaluated
AUDIT-C Score Incidence of Postoperative Complications
1-4 4.8%

5-8 6.9%

9-10 7.5%

11-12 7.5%

Abbreviations: AUDIT-C, Alcohol Use Disorders Identification Test-Consumption.

Risk of Postoperative Complications:
 Reference - J Gen Intern Med 2011 Feb;26(2):162
 alcohol use and major depression
o past alcohol dependence associated with increased risk for major depression
 based on cross-sectional survey
 6,050 United States adults who reported past drinking of at least 12 drinks yearly but had not
used alcohol, tobacco or other drugs within the past 12 months were analyzed for presence
of diagnosis for major depression
 14% had been diagnosed with past alcohol dependence
 current major depression in 8% of persons with past alcohol dependence vs. 2% of persons
without past (adjusted OR 4.2, 95% CI 2.8-6.3)
 past alcohol abuse (negative consequences but not meeting criteria for dependence) was not
associated with depression
 Reference - Arch Gen Psychiatry 2002 Sep;59(9):794
o alcohol abuse and dependence associated with major depression
 based on cohort study
 1,055 children in New Zealand were assessed for DSM-IV alcohol abuse or dependence,
depression, and other variables at ages 17-18, 20-21, and 24-25 years
 alcohol abuse or dependence associated with depression at all ages (population-averaged
odds ratio [OR] 1.9, 95% CI 1.53-2.37)
 alcohol abuse or dependence associated with depression (p = 0.003) in model of best fit
analysis, but depression not associated with alcohol abuse or dependence (suggests alcohol
abuse or dependence is causally related to depression)
 Reference - Arch Gen Psychiatry 2009 Mar;66(3):260
 alcohol use increases risk of gout in dose-dependent fashion
o prospective study of 47,150 men followed for 12 years, 730 confirmed incident cases of gout
o compared with men who did not drink alcohol, multivariate relative risk (RR) of gout was 1.32 for
alcohol consumption 10-14.9 g/day, 1.49 for 15-29.9 g/day, 1.96 for 30-49.9 g/day, and 2.53 for
50 g/day or more
o beer consumption had strongest association, spirits consumption had modest association, wine
consumption did not have significant association
o Reference - Lancet 2004 Apr 17;363(9417):1277 EBSCOhost Full Text, editorial can be
found in Lancet 2004 Apr 17;363(9417):1251 EBSCOhost Full Text, commentary can be
found in Lancet 2004 Jul 17-23;364(9430):246 EBSCOhost Full Text
 alcohol misuse associated with medication nonadherence
o based on cohort of 22,670 participants at Veterans Affairs primary clinics taking statins, oral
hypoglycemic agents or antihypertensives followed for 1 year
o participants stratified to 5 alcohol use categories by Alcohol Use Disorders Identification Test
(AUDIT) questionnaire
o medication adherence defined as having medication available on at least 80% of observation days
o compared to non-alcohol drinkers at 1 year
 adherence to statins significantly lower for severe and moderate alcohol users
 adherence to antihypertensives significantly lower for severe, moderate and mild alcohol
users
 o no differences in adherence to oral hypoglycemic agents
o Reference - Ann Intern Med 2008 Dec 2;149(11):795, editorial can be found in Ann Intern Med
2008 Dec 2;149(11):830
 National Institute for Health and Clinical Excellence (NICE) guideline on diagnosis and clinical
management of alcohol-related physical complications can be found at NICE 2010 Jun:CG100 or
at National Guideline Clearinghouse 2011 Feb 14:23784, summary can be found in BMJ 2010 Jun
16;340:c2942
Prognosis:
 alcohol use disorder associated with increased risk of all-cause mortality (level 2 [mid-
level] evidence)
o based on systematic review of observational studies limited by heterogeneity
o systematic review of 81 observational studies evaluating all cause mortality in 853,722 patients
with alcohol use disorder followed for mean of 2-30 years
o 221,683 deaths observed
o alcohol use disorder associated with increased risk of all-cause mortality in
 men (relative risk [RR] 2.98, 95% CI 2.68-3.31) in analysis of 59 studies with 169,029
deaths, results limited by significant heterogeneity
 women (RR 4.64, 95% CI 3.94-5.47) in analysis of 30 studies with 48,024 deaths, results
limited by significant heterogeneity
o younger age (≤ 40 years old) associated with substantially increased risk mortality among patients
with alcohol use disorder
o Reference - Addiction 2013 Sep;108(9):1562 EBSCOhost Full Text
 heavy drinking (> 22 units/week) associated with increased mortality, no clear benefit
from moderate drinking
o based on prospective cohort study
o 5,766 men aged 35-64 years at 27 workplaces in west of Scotland followed > 21 years
o risk for all-cause mortality similar for nondrinkers and men drinking up to 14 units/week, mortality
risk then increased with increasing alcohol consumption
o increased mortality risk remained significant after adjustment for other risk factors for men
drinking 22 or more units/week
o no strong relation between alcohol consumption and mortality from coronary heart disease after
risk factor adjustment
o strong positive relation seen between alcohol consumption and risk of mortality from stroke
o Reference - BMJ 1999 Jun 26;318(7200):1725
 many primary care patients who screen positive for alcohol misuse indicate some
readiness to change on Drinking Practices Questionnaire
o 62,487 patients who visited general internal medicine clinic 1997-2000 were mailed questionnaires
o 6,551 (55% of patients who responded to questionnaires and screened positive) completed
Drinking Practices Questionnaire
o analysis limited to 6,419 male respondents who also completed AUDIT and readiness-to-change
questions
Precontemplation Contemplation Action
AUDIT score < 8 37% 15% 47%

AUDIT score 8-15 6% 35% 59%

AUDIT score 16-19 2% 42% 56%

AUDIT score 20 or higher 1% 49% 51%

Abbreviation: AUDIT, Alcohol Use Disorder Identification Test.

Responses to Drinking Practices Questionnaire:
o Reference - Ann Fam Med 2006 May-Jun;4(3):213 EBSCOhost Full Text full-text
o DynaMed commentary -- patients with alcohol use who did not complete questionnaire may have
less readiness to change
 sustained reduction in alcohol use more likely to occur with treatment, but many patients
may reduce consumption without treatment (level 2 [mid-level] evidence)
o based on cohort study
 o 628 patients seeking treatment for alcohol use disorder followed for up to 16 years
o alcohol use disorders defined as including substance use problems, dependence symptoms,
drinking to intoxication in past month or perception of alcohol abuse as problem
o alcohol use assessed at 3 and 16 years
o at 16 year follow up
 121 individuals had died
 of remaining 507 individuals, 461 had ≥ 2 follow-up evaluations
 only 99 individuals received no help in first year
 273 had treatment with or without Alcoholics Anonymous (AA) support
 89 individuals only had AA support
o individuals who had either formal treatment or entered AA were similar at baseline and had similar
results, so researchers combined both groups as treatment
o remission defined as all of following
 abstinence or moderate drinking in past 6 months
 no drinking problems in past 6 months
 no intoxication or consumption of more than 3 ounces ethanol in past month
o comparing treated vs. untreated
 remission at 3 years in 62.4% vs. 43.4% (p < 0.01, NNT 5)
 of those in remission at 3 years, relapse at 16 years occurred in 42.9% vs. 60.5% (p < 0.05,
NNT 5)
o Reference - Addiction 2006 Feb;101(2):212 EBSCOhost Full Text full-text
 remission in absence of treatment may occur in 20%-30% of patients (Lancet 2009 Feb
7;373(9662):492)
 insomnia associated with increased risk for relapse within 6 months
o based on cohort study
o based on study of 172 alcoholics
o relapse defined as use of any alcohol
o relapse reported in 60% of patients reporting insomnia at baseline vs. 30% in those without
baseline report of insomnia
o study had 57% loss to follow-up
o Reference - Am J Psychiatry 2001 Mar;158(3):399 full-text
 major depression has substantial impact on remission and relapse rates in 18-month follow-up of 250
patients with cocaine, heroin or alcohol dependence (Arch Gen Psychiatry 2002 Apr;59(4):375 in Am
Fam Physician 2002 Sep 15;66(6):1081)
Prevention and Screening
Prevention:
School-based prevention programs in children and adolescents:
 conflicting evidence regarding effectiveness of universal school-based prevention
programs for alcohol misuse in school-aged children (level 2 [mid-level] evidence)
o based on Cochrane review of mostly low-quality trials
o systematic review of 53 randomized trials (51 with cluster randomization) evaluating universal
school-based prevention programs for alcohol misuse in school-aged children < 18 years old
o heterogeneity of interventions, populations, and outcomes prevented quantitative analysis
o 6 of 11 trials evaluating alcohol-specific interventions reported some evidence of effectiveness
compared to standard curriculum
o 14 of 39 trials evaluating generic interventions reported greater reduction in alcohol use
o inconsistent results found in 3 trials with interventions targeting cannabis, alcohol, and/or tobacco
o most commonly observed positive effects across programs were for drunkenness and binge
drinking
o Reference - Cochrane Database Syst Rev 2011 May 11;(5):CD009113
 Drug Abuse Resistance Education (DARE) appears ineffective in preventing use of alcohol,
tobacco, or illicit drugs (level 2 [mid-level] evidence)
o based on 2 systematic reviews without quality assessment of included trials
o meta-analysis of 11 published controlled trials (Am J Public Health 2004 Jun;94(6):1027
EBSCOhost Full Text full-text)
o meta-analysis of 20 trials (Int J Environ Res Public Health 2009 Jan;6(1):267 full-text)
 o DynaMed commentary -- most of these trials evaluated the "old DARE model" and DARE
prevention program was revised in 2001 so may be more effective, only 2 trials were published
after 2001
 DARE Plus program in seventh grade may reduce drug use in eighth grade
o based on randomized trial
o 24 schools randomized to DARE vs. DARE Plus vs. delayed program control
o DARE Plus activities included youth-led extracurricular activities and community adult action
teams
o 6,237 seventh-grade students evaluated at end of eighth grade
o no significant differences in self-reported tobacco, alcohol, and multidrug use and victimization
between DARE and control groups
o DARE Plus associated with reduced self-reported tobacco, alcohol, and multidrug use and
victimization among boys but no significant differences in outcomes among girls
o Reference - Arch Pediatr Adolesc Med 2003 Feb;157(2):178 full-text, summary can be found
in Am Fam Physician 2003 Aug 1;68(3):550
 Strengthening Families Program (7 family skills training sessions) and Preparing for the
Drug-Free Years (5 family skills training sessions) were each more effective than minimal
contact control in reducing initiation and current use of alcohol, tobacco, and marijuana
at 4 years
o based on randomized trial of 33 public schools
o 667 students in sixth grade at baseline
o Reference - J Consult Clin Psychol 2001 Aug;69(4):627
 teacher-delivered personality-targeted intervention associated with reduced alcohol
consumption in adolescents (level 2 [mid-level] evidence)
o based on cluster-randomized trial without attention control
o 18 schools randomized to teacher-delivered personality-targeted intervention vs. no intervention
with 1,159 high-risk students (mean age 13.7 years) who were followed for 6 months
 teacher-delivered personality-targeted intervention was two 90-minute group sessions (mean
6 students) with psychoeducational, motivational enhancement and cognitive-behavioral
therapies
 teachers received 3 days of training in counseling
 all students received drug education in class as part of national curriculum requirements
o teacher-delivered personality-targeted intervention associated with
 reduced drinking (odds ratio [OR] 0.6, 95% CI 0.4-0.8)
 reduced binge-drinking (OR 0.7, 95% CI 95% CI 0.5-1)
 reduced binge-drinking in alcohol users (OR 0.45, 95% CI 0.3-0.8)
o Reference - J Am Acad Child Adolesc Psychiatry 2010 Sep;49(9):954
 National Institute for Health and Clinical Excellence (NICE) public health guidance on interventions in
schools to prevent and reduce alcohol use among children and young people can be found at NICE
2007 Nov:PH7
Prevention strategies in children and adolescents in non-school settings:
 mentoring of adolescents might reduce initiation of drug and alcohol use (level 2 [mid-
level] evidence)
o based on Cochrane review with limited evidence
o systematic review of 4 randomized trials comparing mentoring to no intervention for prevention
of alcohol or drug use in 1,194 adolescents
o all trials conducted in the United States in nonusers at baseline, with high proportion of minority
and disadvantaged adolescents
o mentoring defined as supportive relationship in which 1 person offers support, guidance, and
concrete assistance based on sharing of experience and expertise without expectation of personal
gain
o 3 trials evaluated initiation of alcohol use
 no significant difference between groups at 6 months in 1 trial with 194 adolescents
 mentoring associated with lower initiation rate at 12 or 18 months in analysis of 2 trials with
1,116 adolescents
 risk ratio 0.71 (95% CI 0.57-0.9)
 NNT 10-42 with 24% initiating alcohol use in no intervention group
o 3 trials evaluated initiation of drug use
  mentoring associated with lower initiation rate at 18 months in 1 trial with 959 adolescents
(6% vs. 11%, p = 0.0046, NNT 20)
 mentoring nonsignificantly associated with lower initiation rate in 1 trial with 194 adolescents
 no significant difference between groups in 1 trial with 157 adolescents
o no significant difference between groups in substance abuse (including alcohol and drugs) within
previous 2 months at 3-year follow-up in 1 trial
o Reference - Cochrane Database Syst Rev 2011 Nov 9;(11):CD007381
 universal multicomponent prevention programs associated with reduction in alcohol
misuse in school-aged children (level 2 [mid-level] evidence)
o based on Cochrane review limited by clinical heterogeneity
o systematic review of 20 randomized and cluster-randomized trials evaluating universal
multicomponent prevention programs (intervention in > 1 setting) for alcohol misuse in school-
aged children ≤ 18 years old
o meta-analysis precluded by heterogeneity of interventions, populations, and outcomes
o control groups were no program in 15 trials, mailed materials in 4 trials, and other active
interventions in 1 trial
o 13 trials reported significant reduction in alcohol use or initiation with universal multicomponent
interventions
o 1 trial found significant benefit of intervention only in subgroup of baseline drinkers
o 6 trials found no significant differences between groups
o Reference - Cochrane Database Syst Rev 2011 Sep 7;(9):CD009307
 universal family-based prevention programs associated with reduction in alcohol misuse
in school-aged children (level 2 [mid-level] evidence)
o based on Cochrane review with clinical heterogeneity
o systematic review of 12 randomized trials evaluating universal family-based prevention programs
for alcohol misuse in school-aged children ≤ 18 years old
o heterogeneity of interventions, populations, and outcomes precluded meta-analysis
o interventions included
 development of parenting skills including parental support, nurturing behaviors, establishing
clear boundaries or rules, and parental monitoring.
 development of skills in teenagers including social and peer-resistance skills, development of
behavioral norms, and positive peer affiliations
o comparison groups included other interventions or no intervention
o family-based prevention programs significantly reduced alcohol use in 9 of 12 trials
o Reference - Cochrane Database Syst Rev 2011 Sep 7;(9):CD009308
 community-based program for adolescents may reduce initiation of alcohol, drug, and
tobacco use, but does not appear to decrease level of use in those who do not abstain
(level 2 [mid-level] evidence)
o based on cluster-randomized trial without intention-to-treat analysis
o 24 communities (population ≤ 50,000 each) were randomized to 1 of 2 interventions for fifth-
grade public school students aged 10-14 years
 community-based program ("Communities That Care") consisted of identification of risk
factors for adolescent problem behaviors within individual communities through youth
surveys followed by implementation of school-, family-, and community-based programs by
community coalition for 5 years
 control intervention consisted of distribution of data from youth surveys once every 2 years
without further assistance
o 4,407 students in 5th grade were enrolled and 90.5% completed follow-up in 12th grade
o all outcomes were self-reported
o sustained abstinence defined as no initiation of use from 5th grade through 12th grade in
students
o comparing community-based program vs. control intervention
 sustained abstinence from alcohol use in 32.2% vs. 23.3% (p < 0.05)
 sustained abstinence from any drug use in 24.5% vs. 17.6% (p < 0.05)
 sustained abstinence from tobacco use in 49.9% vs. 42.8% (p < 0.05)
o no significant differences in cumulative 8-year incidence or in prevalence during past month or
year in nonabstainers
o Reference - JAMA Pediatr 2014 Feb;168(2):122
 community-based substance use prevention programs may reduce alcohol use and daily
smoking in adolescents (level 2 [mid-level] evidence)
o based on cohort study in Iceland
o 3,117 adolescents aged 14-15 years from community-based substance use prevention program
were compared to 1,907 adolescent controls
o substance use prevention program designed to increase levels of parental monitoring and
adolescent engagement in healthy leisure time activities
o substance use prevention program associated with reduced likelihood of
 any alcohol use in last 30 days (odds ratio [OR] 0.89, 95% CI 0.82-0.98)
 alcohol intoxication in last 30 days (OR 0.86, 95% CI 0.78-0.96)
 daily smoking (OR 0.9, 95% CI 0.77-0.99)
o Reference - Prev Med 2010 Aug;51(2):168
 Strong African American Families Program reported to reduce alcohol initiation among
rural African American adolescents
o Strong African American Families Program includes training in
 protective parenting processes (regulated-communicative parenting) including limit setting,
monitoring, racial socialization, clear expectations about alcohol use, communication, and
inductive discipline
 targeted youth protective processes including planful future orientation, resistance efficacy,
negative attitudes toward alcohol use, and negative images of drinking youths
o 8 rural counties in Georgia (United States) were randomized to intervention vs. control
 intervention consisted of 7 weekly meetings at community facilities with separate concurrent
training sessions for parents and children for 1 hour, followed by joint parent-child session
for 1 hour
 control families received 3 mailings regarding general health issues
o subjects were 332 rural African American 11 year olds and their primary caregivers, 305 subjects
analyzed by intent-to-treat
o baseline variables were similar except for negative attitudes toward alcohol use
o over 29 months, intervention reported to be associated with
 fewer adolescents initiating alcohol use
 slower increases in use among adolescents initiating alcohol use
o Reference - J Consult Clin Psychol 2006 Apr;74(2):356
 computer-delivered alcohol abuse prevention program may reduce alcohol use in urban
youths (level 2 [mid-level] evidence)
o based on randomized trial with methodologic limitations
o 513 children (mean age 10.8 years) of mostly Black or Hispanic race/ethnicity randomized to 1 of
3 treatments and followed for 7 years
 computer-delivered alcohol prevention program
 computer-delivered alcohol prevention program plus supplemental parental support material
 control
o methodologic limitations included
 unclear randomization
 unclear allocation concealment
 control not described
o computer-delivered prevention program (with or without supplemental parental support)
associated with reduced (vs. control)
 past 30-days of alcohol consumption (p < 0.05)
 binge drinking (p < 0.05)
 cigarette smoking (p < 0.05)
o Reference - J Adolesc Health 2010 May;46(5):451 full-text
 limited evidence regarding interventions for prevention of drug use by young people
delivered in non-school settings
o based on Cochrane review
o systematic review of 17 studies
o motivational interviewing and some family interventions may have some benefit
o Reference - Cochrane Database Syst Rev 2006 Jan 25;(1):CD005030
 increased frequency of family meals may decrease substance use among adolescents
(level 2 [mid-level] evidence)
o based on 2 observational studies
o increased frequency of family meals (≥ 5 per week) may decrease substance use
among female adolescents (level 2 [mid-level] evidence)
 based on retrospective longitudinal cohort study with high dropout rate
 806 adolescents in public schools completed surveys at mean age 12.7 years and at mean
age 17 years
 ≥ 5 family meals/week associated with reduced
 cigarette smoking (odds ratio [OR] 0.47, 95% CI 0.29-0.75)
 alcohol use (OR 0.49, 95% CI 0.29-0.83)
 marijuana use (OR 0.49, 95% CI 0.26-0.93)
 no significant association with any substance use among males
 Reference - J Adolesc Health 2008 Aug;43(2):151
o increased frequency of family meals associated with decreased substance use and
depressive symptoms in teenagers (level 2 [mid-level] evidence)
 based on cross-sectional survey
 4,734 teenagers (mean age 15 years) in 31 public schools in Minneapolis/St. Paul, Minnesota
area surveyed
 about 25% reported eating 7 or more meals per week with their family
 > 33% reported eating < 3 meals per week with their family
 increased family meal frequency associated with decreasing rates of substance abuse
(tobacco, marijuana, and alcohol), depressive symptoms, suicidal ideation, and increasing
grade-point average (p < 0.05 for each)
 Reference - Arch Pediatr Adolesc Med 2004 Aug;158(8):792 full-text
 National Institute on Alcohol Abuse and Alcoholism (NIAAA) has alcohol prevention web site targeting
sixth to eighth graders (aged 11-13 years) at The Cool Spot
Prevention strategies in college students and young adults:
 individual face-to-face and web-based social norms interventions may reduce alcohol
misuse in college students (level 2 [mid-level] evidence)
o based on Cochrane review of trials with methodologic limitations
o systematic review of 66 randomized trials comparing social norms interventions vs. no
intervention, alcohol education, or non-normative feedback (control) to reduce alcohol misuse in
43,125 university or college students
o most trials had ≥ 1 limitation including
 unclear allocation concealment
 unclear blinding of outcome assessors
 high dropout rate
o social norms interventions designed to correct misperceptions of alcohol use among peers
o comparing individual face-to-face feedback to control
 individual face-to-face feedback associated with fewer alcohol-related problems, reduced
drinking frequency, and decreased quantity of drinking at 3 months and at ≥ 4 months
 for effect on binge drinking
 individual face-to-face feedback associated with decreased binge drinking at 3 months
 no significant difference at ≥ 4 months
o comparing web-based feedback to control
 web-based feedback associated with reduced drinking frequency, reduced quantity of
drinking, and reduced binge drinking at 3 months and at ≥ 4 months
 for alcohol-related problems
 web-based feedback associated with decreased alcohol-related problems at 3 months
 no significant difference at ≥ 4 months
 small effect sizes for all results, most results also limited by significant heterogeneity
o comparing group face-to-face feedback to control
 for alcohol-related problems and drinking frequency
 no significant difference in either outcome at 3 months
 group face-to-face feedback associated with decreased alcohol-related problems and
nonsignificantly reduced drinking frequency at ≥ 4 months
  group face-to-face feedback associated with decreased quantity of drinking and binge
drinking at 3 months
o no significant difference in any outcome comparing mailed feedback vs. control
o Reference - Cochrane Database Syst Rev 2015 Jan 26;(1):CD006748
 brief motivational, on-campus interviews may reduce initiation of heavy episodic drinking
in college students (level 2 [mid-level] evidence)
o based on subgroup analysis of randomized trial
o 1,014 incoming college students randomized to 1 of 4 groups and followed for 22 months
 brief motivational intervention (BMI), including 2 private, in-person sessions on campus and
interactive survey about drinking behaviors
 parent-based intervention (PBI) including handbook mailed to parents to raise awareness
and encourage communication with teens about alcohol abuse
 BMI plus PBI
 assessment only
o heavy episodic drinking defined as consumption of ≥ 5 drinks in a row for men or ≥ 4 for women
o 17-item screening tool assessed alcohol-related consequences during previous 3 months
(including hangover, driving after drinking, sickness, absenteeism, violence)
o 51% of students reported no heavy episodic drinking at baseline
o comparing BMI vs. non-BMI in subgroup of students not reporting heavy episodic drinking at
baseline
 heavy episodic drinking reported in 44.8% vs. 57% (no p value +
 reported, NNT 9)
 alcohol-related consequences reported in 46.7% vs. 55.4% (no p value reported, NNT12)
o Reference - J Consult Clin Psychol 2010 Jun;78(3):349
 brief motivational intervention may reduce drinking in young men with history of binge
drinking (level 2 [mid-level] evidence)
o based on randomized trial without intention-to-treat analysis
o 622 men (mean age 20 years) randomized to single face-to-face brief motivational intervention
vs. no intervention during mandatory army conscription in Switzerland
o brief motivational intervention was 15 minute meeting with trained counselor to discuss alcohol
use and increase awareness of consequences
o 88.7% completed 6-month follow-up and were included in analysis
o brief motivational intervention associated with 20% reduction in weekly alcohol use vs. control (p
= 0.03) in subgroup of 235 men with history of binge drinking
o no significant difference in weekly alcohol use in subgroup of 136 men without history of binge
drinking
o Reference - Drug Alcohol Depend 2011 Jan 1;113(1):69
Other prevention strategies:
 mass media campaigns appear to reduce drinking and driving and alcohol-related crashes
(level 2 [mid-level] evidence)
o based on systematic review
o systematic review of 8 studies, mostly before-and-after design
o 2 studies reported 30%-37% reductions in drivers over the alcohol limit, 4 studies reported 6%-
18% reductions in total crashes, alcohol-related crashes, injury-related crashes, and fatal crashes,
2 studies reported multimillion dollar cost savings
o Reference - Am J Prev Med 2003 Jul;27(1):57 in Bandolier 2004 Aug;126:5
Screening:
Overview:
 screening tests effective in identifying patients in primary care setting
 United States Preventive Services Task Force (USPSTF) recommends screening adults ≥ 18 years old
for alcohol misuse and providing persons engaging in risky or hazardous drinking with brief behavioral
counseling to reduce alcohol misuse (USPSTF Grade B)(3)
 computerized version of Alcohol Use Disorders Identification Test (AUDIT) questionnaire plus other
screening questions can be found at AlcoholScreening.org
 details on 10 different screening tests for alcohol (and other substance) use disorders can be found
at Project Cork
 National Institute on Drug Abuse (NIDA) Drug Screening Tool which supports clinician in screening for
use and risk with alcohol, tobacco, prescription drugs, and illicit drugs can be found at NIDA-Modified
ASSIST
 Point of Care guide with 1-3 screening questions for each of depression, alcohol problems, and
domestic violence can be found in Am Fam Physician 2004 May 15;69(10):2421
 systematic review of accuracy of screening methods for alcohol problems in primary care supports use
of formal screening instruments AUDIT and CAGE (Arch Intern Med 2000 Jul 10;160(13):1977),
commentary can be found in Arch Intern Med 2001 Mar 26;161(6):895
AUDIT:
 AUDIT and RAPS4 questionnaires more accurate than CAGE and TWEAK questionnaires
for assessing alcohol dependence in emergency department setting (level 1 [likely
reliable] evidence)
o based on diagnostic cohort study
o 3,624 adults presenting to emergency department in Argentina, Mexico, and United States were
surveyed using AUDIT, CAGE, RAPS4, and TWEAK questionnaires
o alcohol dependence during past year was assessed using Alcohol Section of Composite
International Diagnostic Interview Core (reference standard)
o data reported using only 2,105 survey responders who consumed ≥ 1 drink during past year
o prevalence of alcohol dependence was 9% in Argentina, 12% in Mexico, and 19% in United
States by reference standard
o for detection of alcohol dependence, compared to reference standard
 AUDIT had
 92%-94% sensitivity
 80%-98% specificity
 CAGE had
 75%-96% sensitivity
 64%-87% specificity
 RAPS4 had
 89%-95% sensitivity
 75%-98% specificity
 TWEAK had
 90%-98% sensitivity
 67%-98% specificity
o Reference - Addict Behav 2010 Sep;35(9):818
 Alcohol Use Disorders Identification Test (AUDIT) questionnaire (10 items) had higher sensitivity
(66%-84%) and higher specificity (83%-98%) than all of 4 biochemical markers (gamma-
glutamyltransferase [GGT], aspartate aminotransferase [AST], mean corpuscular volume [MCV],
carbohydrate-deficient transferrin [CDT]) for hazardous drinking, binge drinking and alcohol
dependence in study of 194 men attending primary care (BMJ 2006 Mar 4;332(7540):511 full-text),
commentary can be found in BMJ 2006 Mar 18;332(7542):667
 AUDIT for United States audience available online from National Institute on Alcohol Abuse and
Alcoholism
 AUDIT superior to CAGE in detecting alcohol problems (Ann Intern Med 1998 Sep 1;129(5):353 in ACP
Journal Club 1999 Mar-Apr;130(2):43)
AUDIT-C:
 AUDIT-C is the 3 consumption questions from the 10-item Alcohol Use Disorders Identification Test
(AUDIT)
o "How often do you have a drink containing alcohol?" 0 points for never, 1 point for monthly or
less, 2 points for 2-4 times/month, 3 points for 2-3 times/week, 4 points for 4 days/week or more
o "How many drinks containing alcohol do you have on a typical day when you are drinking?" 0
points for not drinking, 1 point for 1-4 drinks, 2 points for 5-6 drinks, 3 points for 7-9 drinks, 4
points for 10 or more drinks
o "How often do you have 6 or more drinks on one occasion?" 0 points for never, 1 point for less
than monthly, 2 points for monthly, 3 points for weekly, 4 points for daily or almost daily
 3-question version of AUDIT (AUDIT-C)
o inconclusive evidence of equivalence between AUDIT-C and AUDIT for identifying unhealthy
alcohol use
  based on systematic review of 14 studies with methodological heterogeneity
 Reference - Ann Intern Med 2008 Dec 16;149(12):879, editorial can be found in Ann Intern
Med 2008 Dec 16;149(12):904, commentary can be found in Ann Intern Med 2009 Mar
17;150(6):430
o AUDIT-C score of ≥ 3 has 94.9% sensitivity and 68.8% specificity for identifying hazardous
drinking compared to full AUDIT score of ≥ 8
 based on cross sectional survey of 13,438 primary care patients
 Reference - J Fam Pract 2001 Apr;50(4):313 EBSCOhost Full Text, editorial can be
found in J Fam Pract 2001 Apr;50(4):321
o for identifying hazardous drinking or alcohol use disorder in women, AUDIT-C more sensitive but
less specific than single question about frequency of heavy drinking
 based on study of women receiving care at Veterans Affairs facilities in Seattle area
 393 women completed health questionnaire and then had in-person interviews including
AUDIT-C plus modified third question with sex-specific threshold (4 or more drinks per
occasion)
 89 women (23%) met interview criteria for hazardous drinking and/or active alcohol abuse or
dependence
 standard AUDIT-C score ≥ 2 had 81% sensitivity and 86% specificity
 AUDIT-C score ≥ 2 with sex-specific third question had 84% sensitivity and 85% specificity
 AUDIT-C approaches had positive likelihood ratio of 5.7-5.9
 reporting 4 or more drinks on one occasion in past year had 69% sensitivity and 94%
specificity with positive likelihood ratio of 11
 Reference - Arch Intern Med 2003 Apr 14;163(7):821
CAGE:
 CAGE criteria - 2 or more positive answers
o C - Have you ever felt the need to cut down on your drinking?
o A - Have you ever felt annoyed by criticism of your drinking?
o G - Have you ever felt guilty about your drinking?
o E - Have you ever taken a drink (eye opener) first thing in the morning?
 Reference - Arch Fam Med 2000 Sep-Oct;9(9):814 full-text
 sensitivity of CAGE questionnaire depends on population
o systematic review of 10 studies comparing CAGE questionnaire screening with DSM criteria for
alcohol abuse or dependence
o 2 or more positive questions on CAGE questionnaire had 87% sensitivity in inpatients
o 71% sensitivity in primary care patients, 60% sensitivity in ambulatory patients
o positive likelihood ratio 3.44 and negative likelihood ratio 0.18
o Reference - J Clin Epidemiol 2004 Jan;57(1):30, commentary can be found in Evidence-Based
Medicine 2005 Jan-Feb;10(1):26
 CAGE performed poorly in detecting heavy or binge drinkers among older adults
o 5,065 consecutive consenting patients > 60 years old among 88 primary care physicians in
southeastern Wisconsin screened with both CAGE and questions about quantity/frequency of
regular drinking in last 3 months and number of episodes of binge drinking
o fewer than half of patients were CAGE positive using standard cutoff of 2 positive answers
o on CAGE questionnaire, only 9% men and 3% women screened positive for alcohol abuse within
3 months
o results from beverage-specific questions
o > 5 drinks per occasion
 15% men and 12% women regularly drank in excess (defined as > 7 drinks/week for women
and > 14 drinks/week for men
 9% men and 2% women reported drinking > 21 drinks/week
o Reference - JAMA 1996 Dec 25;276(24):1964
T-ACE:
 T-ACE–modified CAGE–2 or more positive answers
o T - Does it take more than it used to for you to get high? (Tolerance)
o Have you become Angry or Annoyed when others express concern about your use?
o Have you tried to Cut down or quit?
 o Have you had an Eye opener?
 Reference - Project Cork website
 modified T-ACE criteria may be more accurate than AUDIT or CAGE criteria (especially in pregnant
women)
o cross-sectional survey of 300 patients > 18 with scheduled appointments at a hospital-based
outpatient clinic that is the primary teaching site for a family practice residency program in the
Northeast United States, only 300 of 1,021 potentially eligible patients were interviewed so
selection bias may alter results, 17.7% lifetime prevalence of DSM-IV criteria for abuse or
dependence
o CAGE criteria - 2 or more positive answers
 C - Have you ever felt the need to cut down on your drinking?
 A - Have you ever felt annoyed by criticism of your drinking?
 G - Have you ever felt guilty about your drinking?
 E - Have you ever taken a drink (eye opener) first thing in the morning?
o T-ACE - modified to 2 or more positive answers
 T (tolerance) question replaces G (guilt) question of CAGE, C is attempts to cut down
 T - How many drinks does it take to make you feel high?
o AUDIT - Alcohol Use Disorders Identification Test - positive if 4 or more
o performance characteristics for abuse or dependence
 in women
 CAGE had 65% sensitivity, 92% specificity
 T-ACE had 70% sensitivity, 92% specificity
 AUDIT had 62% sensitivity, 79% specificity
 in men
 CAGE had 69% sensitivity, 93% specificity
 T-ACE had 81% sensitivity, 86% specificity
 AUDIT had 81% sensitivity, 77% specificity
o Reference - Arch Fam Med 2000 Sep-Oct;9(9):814 full-text
Other screening tests in primary care:
 National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommended single-
question screening in primary care setting may identify unhealthy alcohol use
o based on cross-sectional cohort of 286 patients in primary care waiting rooms
o patients were asked "How many times in the last year have you had X or more drinks in a day?"
 X = 5 for men, 4 for women
 response > 1 considered positive
o single-question screening recommended by NIAAA
o unhealthy alcohol use defined as 1 of
 presence of alcohol use disorder determined by standard diagnostic interview
 risky consumption determined by 30-day calendar method
o predictive performance for positive screening had
 for unhealthy alcohol use, sensitivity 81.8% and specificity 79.3%
 for alcohol use disorder, sensitivity 87.95, specificity 66.8%
o Reference - J Gen Intern Med 2009 Jul;24(7):783
 one or two questions can identify problem drinking
o single alcohol screening question (SASQ) is "When was the last time you had more than X drinks
in one day?" with X = 5 for men and X = 4 for women
o "within 3 months" considered a positive screen
o 1 drink = 12 ounces of beer, 5 ounces of wine, 1.5 ounces of liquor or 14 g ethanol
o study subjects were 1,537 patients presenting to emergency department with acute injury, 1,151
patients presenting to emergency department with medical illness and 1,112 community controls
interviewed by telephone
o hazardous drinking defined as > 4 drinks in 1 day or > 14 drinks in 1 week in men, or > 3 drinks
in 1 day or > 7 drinks in 1 week for women
o SASQ had 85% sensitivity and 70% specificity in men, and 82% sensitivity and 77% specificity in
women
o SASQ did not perform consistently across all 3 study groups
 o area under receiver operating curve (a marker of diagnostic accuracy, ranging from 0 to 1, with 1
being perfect and 0.5 being useless clinically) for identifying hazardous drinking or current alcohol
use disorder (DSM-IV criteria) was 0.81 for SASQ, 0.8 for single question about average quantity
alone, and 0.85 for product of usual frequency times average quantity
o Reference - Alcohol Alcohol 2005 May-Jun;40(3):208
 single question can identify problem drinking
o question is "When was the last time you had more than X drinks in 1 day? with X = 5 for men
and X = 4 for women"
o based on cross-sectional study of 1,432 men and 1,085 women in 3 emergency departments in
Missouri with 74% participation rate
o 35% had problem drinking defined as either hazardous drinking in 29-day retrospective interview
(29%) or alcohol use disorder in past year (20%)
o positive response within 3 months had 88% sensitivity and 81% specificity in men and 83%
sensitivity and 91% specificity in women for problem drinking
o Reference - J Fam Pract 2001 Apr;50(4):307 EBSCOhost Full Text, editorial can be found in
J Fam Pract 2001 Apr;50(4):321, commentary can be found in J Fam Pract 2001 Aug;50(8):713
 single question screening and CAGE screening had similar comfort among clinicians and
patients
o 31 clinicians in Missouri and 13 clinician-researchers across United States were randomized in
crossover trial to use single question screening ("When was the last time you had more than X
drinks in one day?") vs. CAGE questionnaire
o 2,800 patients provided data, 80%-90% clinicians and 70% patients reported being comfortable
with screening and ensuing discussion with no significant differences
o Missouri clinicians screening more patients with single question than with CAGE (81% vs. 69%, p
= 0.001) while clinician-researchers had higher screening rates with either approach (97% vs.
96%)
o Reference - Ann Fam Med 2004 Sep-Oct;2(5):398 EBSCOhost Full Text full-text
 2-question screening can identify both alcohol and other substance abuse
o two screening questions are "In the last year, have you ever drunk or used drugs more than you
meant to?" and "Have you felt you wanted or needed to cut down on your drinking or drug use in
the last year?"
o study of 1,136 primary care patients aged 18-59 years
o likelihood of current substance abuse disorder was 7.3% if negative responses, 36.5% if 1
positive response and 72.4% if 2 positive responses
o Reference - J Am Board Fam Pract 2001 Mar-Apr;14(2):95 PDF
o DynaMed commentary -- study used multiple (5 or 9) questions and then analyzed the effect of 2
questions, so not actually equivalent to using 2-question screening; THIS SCREENING APPROACH
SHOULD BE VALIDATED in a separate study before clinical application, commentary can be found
in J Fam Pract 2001 Jun;50(6):548
 Short Michigan Alcoholism Screening Test-Geriatric Version (SMAST-G) and CAGE identify
different patients
o 1,889 persons > 55 years old were screened with Short Michigan Alcoholism Screening Test-
Geriatric Version (SMAST-G) and CAGE
o 26% screened positive on at least one test, but < 50% those screening positive on one test
screened positive on the other
o Reference - J Am Geriatr Soc 2002 May;50(5):858 EBSCOhost Full Text
Screening recommendations:
 United States Preventive Services Task Force (USPSTF) recommendations(3)
o USPSTF recommends screening adults ≥ 18 years old for alcohol misuse and providing persons
engaging in risky or hazardous drinking with brief behavioral counseling to reduce alcohol misuse
(USPSTF Grade B)
o insufficient evidence to assess balance of benefits and harms of screening and behavioral
counseling in primary care settings to reduce alcohol misuse in adolescents (USPSTF Grade I)
 American Geriatrics Society (AGS) recommends asking all patients 65 years or older about alcohol use
at least annually to identify possible alcohol use disorders (Annals of Long-Term Care 2006
Jan;14(1):23)
Other considerations in screening:
 opportunistic screening and referral in emergency department may reduce alcohol misuse
and emergency department re-attendance (level 2 [mid-level] evidence)
o based on randomized trial with high dropout rate
o 599 patients attending a London emergency department screened positive for alcohol misuse by
Paddington Alcohol Test and randomized to receive appointment card vs. control (blank) card
o positive screen by Paddington Alcohol Test for any of
 patient who believes emergency department visit could be related to alcohol
 man drinking > 8 units (1 unit = 8 ounces beer or equivalent) of alcohol in 1 session at least
weekly
 woman drinking > 6 units of alcohol in 1 session at least weekly
o appointment card asked patient to follow-up with alcohol health worker at next available 30-
minute appointment
o both groups received "Think Don't Drink" information leaflet
o 363 patients interviewed at 6-month follow-up, 384 patients interviewed at 12 month followup
o comparing in referral vs. control groups
 weekly alcohol consumption at 6 months, 59.7 vs. 83.1 units (p = 0.02)
 weekly alcohol consumption at 12 months 57.2 vs. 70.8 units (p = 0.09),
 emergency department visits (mean) over 12 months 1.2 vs. 1.7 (p = 0.046)
o Reference - Lancet 2004 Oct 9;364(9442):1334 EBSCOhost Full Text, editorial can be
found in Lancet 2004 Oct 9-15;364(9442):1289 EBSCOhost Full Text, summary can be
found in Am Fam Physician 2005 Sep 1;72(5):914
 2-question instrument may be helpful in identifying alcohol misuse among youths in
emergency department (level 2 [mid-level] evidence)
o based on systematic review limited by heterogeneity
o systematic review of 6 studies evaluating 11 instruments for universal or targeted screening of
alcohol and other drug misuse in patients ≤ 21 years old in emergency department
o clinical heterogeneity in patient populations and instruments prevented meta-analysis of
diagnostic studies
o reliability and validity of instruments evaluated in relation to Alcohol Use Disorders Identification
Test (gold standard)
o instruments including following diagnostic questions (based on DSM-IV criteria) more effective
than other instruments in detecting alcohol abuse and dependence (sensitivity 88%, specificity
90%)
 "In the past year, have you sometimes been under the influence of alcohol in situations
where you could have caused an accident or gotten hurt?"
 "Have there often been times when you had a lot more to drink than you intended to have?"
o Reference - Pediatrics 2011 Jul;128(1):e180
 clinical impression in adolescents greatly underestimates alcohol and drug problem use
(level 2 [mid-level] evidence)
o based on secondary analysis of cohort study
o secondary analysis of validation study of CRAFFT substance abuse screening test with 533
medical clinical patients aged 14-18 years and 109 corresponding clinicians
o clinicians recorded clinical impression on study forms, reference standard was structured
diagnostic interview
o patients were classified on level of alcohol and drug use
 none
 minimal use (if no reported problems)
 problem use (if no abuse or dependence)
 abuse (based on DSM-IV criteria without dependence)
 dependence (3 of 7 diagnostic criteria)
o clinical impression identified only 18 of 101 patients with alcohol or drug problem use, only 10 of
50 patients with alcohol or drug abuse, and none of 36 patients with alcohol or drug dependence
o Reference - Pediatrics 2004 Nov;114(5):e536 EBSCOhost Full Text full-text
 clinical interview may have low sensitivity for identifying alcohol problems in primary
care, hospital, and mental healthcare settings (level 2 [mid-level] evidence)
o based on systematic review with wide confidence intervals
 o systematic review of 48 studies evaluating the ability of clinicians to evaluate alcohol problems in
patients
o specific interview methods were not described
o diagnostic performance of interview-based evaluation of alcohol problems in primary care setting
including 12 studies of 10,997 patients
 sensitivity 41.7% (95% CI 23%-61.7%)
 specificity 93.1% (95% CI 86.7%-97.6%) in analysis of 2 studies
o diagnostic performance of interview-based evaluation of alcohol problems in hospital setting
including 23 studies of 10,837 patients
 sensitivity 52.4% (95% CI 35.9%-68.7%)
 specificity 93.1% (95% CI 89.1%-96.3%) in analysis of 9 studies
o diagnostic performance of interview based evaluation of alcohol problems in mental healthcare
setting including 4 studies of 384 patients
 sensitivity 54.7% (95% CI 16.8%-89.6%)
 specificity 83.6% (95% CI 56.3%-98.9%)
o Reference - Br J Psychiatry 2012 Aug;201:93
 health questionnaires for screening in general practice may not be feasible
o systematic review of 8 randomized trials of brief intervention for excessive alcohol use, all 8 trials
used health questionnaires for screening
o for 1,000 screened patients, 90 screened positive, 25 qualified for brief intervention, and 11
reported drinking less than maximum recommended level at 1 year (compared to 8 in control
group)
o number needed to screen and treat 385 (95% CI 294-588) to change 1 drinker
o Reference - BMJ 2003 Sep 6;327(7414):536 full-text, correction can be found in BMJ 2004 Jan
10;328(7431):96, commentary can be found in J Fam Pract 2004 Jan;53(1):15 EBSCOhost
Full Text, commentary can be found in Am Fam Physician 2004 Apr 1;69(7):1774
 alcohol use screening in primary care appears cost-effective
o based on literature review of 16 studies
o Reference - Am J Prev Med 2008 Feb;34(2):143
 computer-assisted self-administered screening and assessment by patients 65 or older
before office visit might reduce hazardous and harmful drinking (level 2 [mid-level]
evidence), based on cluster randomized trial with 665 patients, but complex reporting of combined
outcomes limits clinical interpretation (J Am Geriatr Soc 2005 Nov;53(11):1937 EBSCOhost Full
Text), correction can be found in J Am Geriatr Soc 2008 Jun;56(6):1165
 review of screening instruments can be found at Adv Stud Med 2006 Mar;6(3):137 PDF
 composite screening questionnaire for somatoform disorder, anxiety disorder, depressive disorder,
and alcohol abuse from Aarhus University Hospital Research Unit for Functional Disorders has been
described in Fam Pract 2005 Aug;22(4):428 full-text