3/1/16

BH  Meds  
Behavioral  Health  Medica1ons  
ATTC  Mid-­‐America  
2016  
Part  3  

Dr.  Merrill  Norton  Pharm.D.,D.Ph.,ICCDP-­‐D  

Clinical  Associate  Professor  
University  of  Georgia  College  of  Pharmacy  
Athens,  Georgia  
mernort@uga.edu  
3/1/16   Dr.Merrill  Norton  Pharm.D.,D.Ph.,ICCDP-­‐D   1  

Agenda  
•  Generic  and  Brand  Medica1on  Names  
•  Purpose  
•  Usual  Dose  and  Frequency  
•  Poten1al  Side  Effects  
•  Emergency  Condi1ons  
•  Cau1ons  
•  Substance  Use  Disorders  Treatment  
Medica1ons  

3/1/16   Dr.Merrill  Norton  Pharm.D.,D.Ph.,ICCDP-­‐D   2  

Permissions  

•  This  publica1on  was  prepared  by  the  Mid-­‐America  Addic1on  Technology  Transfer  
•  Center  (Mid-­‐America  ATTC)  under  a  coopera1ve  agreement  from  the  Substance  Abuse  
•  and  Mental  Health  Services  Administra1on’s  (SAMHSA)  Center  for  Substance  Abuse  
•  Treatment  (CSAT).  All  material  appearing  in  this  publica1on  except  that  taken  directly  
•  from  copyrighted  sources  is  in  the  public  domain  and  may  be  reproduced  or  copied  
•  without  permission  from  SAMHSA/CSAT  or  the  authors.  Cita1on  of  the  source  is  
•  appreciated.  
•  At  the  1me  of  publica1on,  Pamela  S.  Hyde,  JD,  served  as  the  SAMHSA  Administrator.  
•  H.  Westley  Clark,  MD,  JD,  MPH,  served  as  CSAT  Director,  and  Suzan  Swanton,  
•  LCSW-­‐C,  Public  Health  Advisor,  served  as  the  ATTC  Network  Project  Officer.  
•  The  opinions  expressed  herein  are  the  views  of  the  authors  and  do  not  necessarily  
•  reflect  the  official  posi1on  of  the  Department  of  Health  and  Human  Services  (DHHS),  
•  SAMHSA  or  CSAT.  No  official  support  or  endorsement  of  DHHS,  SAMHSA  or  CSAT  
•  for  the  opinions  described  in  this  document  is  intended  or  should  be  inferred.  

3/1/16   Dr.Merrill  Norton  Pharm.D.,D.Ph.,ICCDP-­‐D   3  

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Table  of  Contents  

•  An1psycho1cs/Neurolep1cs  .  5  
•  Medica1on-­‐Induced  Symptoms  Treatment.  11  
•  An1-­‐manic  Medica1ons/Mood  Stabilizers.  13  
•  An1depressant  Medica1ons  .  17  
•  An1anxiety  Medica1ons  .  22  
•  S1mulant  Medica1ons.  .  27  
•  Narco1c  and  Opioid  Analgesics  .  30  
•  Hypno1cs  (Sleep  Aids)  .  33  
•  Alcohol  Use  Disorder  Treatment  Medica1ons  .  36  
•  Opioid  Use  Disorder  Treatment  Medica1ons  .  40  
•  Tobacco  Use  Disorder  Treatment  Medica1ons  .    44  
•  Other  Substance  Use  Disorders  Treatment  Medica1ons.48  

3/1/16   Dr.Merrill  Norton  Pharm.D.,D.Ph.,ICCDP-­‐D   4  

An1depressant  Medica1ons    

3/1/16   Dr.Merrill  Norton  Pharm.D.,D.Ph.,ICCDP-­‐D   5  

An1depressant  Classifica1ons  
•  SSRIs  —  Selec*ve  Serotonin  Reuptake  Inhibitors  
•  citalopram                Celexa  
•  escitalopram        Lexapro  
•  fluoxe1ne                  Prozac,  Prozac  Weekly,  Sarafem  
•  fluvoxamine          Luvox  
•  paroxe1ne              Paxil,  Paxil  CR  
•  sertraline                  Zolof  
•  vilazodone              Viibryd  
3/1/16   Dr.Merrill  Norton  Pharm.D.,D.Ph.,ICCDP-­‐D   6  

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An1depressant  Classifica1ons  
•  SNRIs  —  Serotonin  Norepinephrine  Reuptake  
•  Inhibitors  
•  desvenlafaxine                  Pris1q  
•  duloxe1ne                                Cymbalta  
•  levomilnacipran            Fetzima  
•  venlafaxine                              Effexor,  Effexor  ER  

3/1/16   Dr.Merrill  Norton  Pharm.D.,D.Ph.,ICCDP-­‐D   7  

An1depressant  Classifica1ons  
•  Other  an*depressants  
•  bupropion  Wellbutrin,  Wellbutrin  SR  
Wellbutrin  XL  
•  mirtazapine  Remeron,  Remeron  SolTab  
•  trazodone        Desyrel  

3/1/16   Dr.Merrill  Norton  Pharm.D.,D.Ph.,ICCDP-­‐D   8  

An1depressant  Classifica1ons  
•  Tricyclics  &  quatracyclics  
•  amitriptyline                Elavil  
•  amoxapine                      Asendin  
•  clomipramine            Anafranil  
•  desipramine                Nopramin  
•  doxepin                                Sinequan  
•  imipramine                    Tofranil  
•  mapro1line                    Ludiomil  
•  nortriptyline                Aventyl,  Pamelor  
•  protriptyline                Vivac1l  
•  trimipramine              Surmon1l  

3/1/16   Dr.Merrill  Norton  Pharm.D.,D.Ph.,ICCDP-­‐D   9  

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An1depressant  Classifica1ons  
•  Monoamine  Oxidase  (MAO)  Inhibitors  
•  isocarboxazid                    Marplan  
•  phenelzine                              Nardil  
•  Selegiline                                    Generic  
•  transdermal  patch      EMSAM  
•  tranylcypromine            Parnate  

3/1/16   Dr.Merrill  Norton  Pharm.D.,D.Ph.,ICCDP-­‐D   10  

Purpose  
•  An1depressant  medica1ons  are  used  to  treat  a  
•  variety  of  mental  health  condi1ons  including  
•  depression,  bipolar  illness,  and  anxiety  disorders.  
•  Most  an1depressants  must  be  taken  for  
•  a  period  of  3  to  4  weeks  to  begin  to  reduce  or  
•  take  away  the  symptoms  of  depression  but  a  
•  full  therapeu1c  effect  may  not  be  present  for  
•  several  months.  

3/1/16   Dr.Merrill  Norton  Pharm.D.,D.Ph.,ICCDP-­‐D   11  

SSRI Forms Start Dose +/- by Max Dose +RCT FDA Approval
Evid.
Fluoxetine Tab, 10 mg 5-10mg 60mg Y 8-17
liquid
Sertraline Tab, 25mg 12.5-25 200mg Y N
liquid mg
Citalopram Tab, 10mg 10mg 40mg Y N
liquid

Escitalopram Tab, 5mg 5mg 20mg Y 12-17

liquid

Paroxetine Tab, 10mg 10mg 60mg N N

liquid
Fluvoxamine Tab, 25mg BID 25mg 300mg N N
liquid

Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-

3/1/16 D 12

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SSRI antidepressants
Atypical antidepressants
Tricyclic antidepressants
MAOI antidepressants
Older mood stabilizers
Newer mood stabilizers
Older antipsychotics
Newer antipsychotics
Anticholinergics
Benzodiazepines
Other anxiolytic/hypnotics
Stimulants
Meds for dementia
Meds for substance abuse
Psychiatric uses of
antihypertensives
SSRI antidepressants
Atypical
antidepressants
Tricyclic antidepressants
MAOI antidepressants
Older mood stabilizers
Newer mood stabilizers
Older antipsychotics
Newer antipsychotics
Anticholinergics
Benzodiazepines
Other anxiolytic/hypnotics
Stimulants
Meds for dementia
Meds for substance abuse
Psychiatric uses of
antihypertensives
LT:Channel Selectivity- How do
channels select for particular ions?
3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D
3/1/16
Selective Serotonin
Reuptake Inhibitor
!  1988 Prozac introduced
!  1992-93 Zoloft, Paxil, Luvox
!  1998 Celexa
!  2001 fluoxetine (Prozac generic)
!  2002 Lexapro (modified Celexa)
!  2006 STAR*D trial results published
http://www.nmha.org/research/star/faqs.cfm
Annual sales = $17 billion
Number of patient starts on Prozac, Paxil or
Zoloft from 1988 to 2009 = 107.5 million
(www.ahrp.org)
Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-
3/1/16 D 13
Newer antidepressants that are
not/less serotonin specific or
affect serotonin differently than
SSRIs
1981- Desyrel (trazodone)
1989- Wellbutrin (bupropion)
1993- Effexor (venlafaxine)
1994- Serzone (nefazodone)
1996- Remeron (mirtazapine)
2004- Serzone discontinued although generics
still available
2004- Duloxetine (Cymbalta)
2009- Desvenlafaxine (Pristiq)
2011- Vilazodone (Viibryd)
2013- Levomilnacipran(Fetzima)
2014- Vortioxetine( Brintellix)
Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-
3/1/16 D 14


= 23
(smaller but stronger)
= 39
(larger but weaker)
15
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2: Channels respond to intracellular and extracellular signals-


The Neurobiology of Learning

extracellular intracellular
intracellular

Q: How can we isolate individual channels in a whole cell prep?

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 16

8: Synaptic Transmission!!

If you thought I got excited about Action Potentials, just wait!!!
F 5.1

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 17

9:Electrical Synapses; Gap Junctions

Conduct ions (Ca+2,K+, Na+, Cl- ), Action Potentials, 2nd Messengers & ATP

How do we know?
Fast Action Potential
Transfer

Delay = < 1ms

F 3/1/16
5.2 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 18

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SSRI antidepressants
Mechanism of action
!  Inhibit serotonin reuptake so increase synaptic serotonin levels
!  Many SSRIs affect other receptors especially at high doses
!  Clinical effect usually takes weeks so mechanism goes beyond
simply increasing synaptic serotonin levels
!  Several serotonin (5-HT) receptor subtypes
!  Serotonin receptors are located throughout the body (especially
GI tract)
!  Histamine, NE/Epi, Melatonin,Neuropeptides also involved

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 19

SSRI antidepressants
Half-life
!  Short: paroxetine & fluvoxamine (missed doses
can result in uncomfortable symptoms)

!  Moderate: sertraline, citalopram, escitalopram

!  Long: fluoxetine (good for people who may miss

doses)

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 20

SSRI antidepressants
Side effects
!  Decreased sex drive and impaired sexual function
tend not to resolve with time
!  Nausea, diarrhea, anorexia, vomiting
- all increase with dose and can resolve with time
!  Weight gain (esp. paroxetine) after initial GI effects
!  Headache, dizziness, anxiety (esp. fluoxetine), rash,
insomnia, sedation, sweating, vivid dreams, tremor,
dry mouth (esp. paroxetine), bruising, ↑ prolactin

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 21

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SSRI antidepressants
Drug-drug interactions (DDI)
!  Luvox > Prozac > Paxil > Zoloft > Celexa > Lexapro
!  Interacting effects may be dose dependent (Zoloft)
!  SSRI levels tend not to be altered by other drugs but
can potentially increase levels (inhibit metabolism) of
certain drugs
!  Examples:
"  paroxetine > ↑ risperidone
"  fluoxetine > ↑ buspirone
"  fluvoxamine > ↑ olanzapine
(consult references such as www.drug-interactions.com , www.drugs.com, others)

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 22

SSRI antidepressants
Cautions
!  Suicidal ideation and ↑ suicide risk especially with children
early in tx but significant debate
!  Serotonin syndrome (SSRI + MAOI, possibly lithium, others)
>> diarrhea, tremor, sweating, restlessness, hyperreflexia
progression of symptoms if untreated ► ► ►
>> disorientation, rigidity, fever >> coma, seizures >>
>> death (approximately 10% mortality rate)
!  Many medications/substances have serotonin activity:
dextromethorphan, fentanyl, meperidine, sumatriptan,
St John’s Wort, MDMA (ecstasy), LSD, many others…

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 23

Atypical antidepressants
SSRI antidepressants
Atypical
antidepressants
Tricyclic antidepressants
MAOI antidepressants
Older mood stabilizers
Newer mood stabilizers
Older antipsychotics
Newer antipsychotics
Anticholinergics
Benzodiazepines
Other anxiolytic/hypnotics
Stimulants
Meds for dementia
Meds for substance abuse
Psychiatric uses of
antihypertensives
Newer antidepressants that are not/
less serotonin specific or affect
serotonin differently than SSRIs
1981- Desyrel (trazodone)
1989- Wellbutrin (bupropion)
1993- Effexor (venlafaxine)
1994- Serzone (nefazodone)
1996- Remeron (mirtazapine)
2004- Serzone discontinued although
generics still available
2004- Duloxetine (Cymbalta)
2009- Bupropion( Aplenzin)
Milnacipran( Savella)
Dexvenlafaxine (Pristiq)

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 24

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Atypical antidepressants
Mechanism of action
!  venlafaxine and duloxetine are both serotonin and
norepinepherine reuptake inhibitors- “SNRIs”
!  mirtazapine has serotonin subtype & norepinephrine
activity
!  trazodone, nefazodone have different serotonin activity
than SSRIs
!  bupropion has dopamine and norepinephrine activity

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 25

Atypical antidepressants
Indications & off-label uses
!  All have FDA approval to treat depression
!  SNRIs shown effective in chronic neuropathic pain
!  Nicotine addiction (bupropion)
!  Augment SSRIs, reduce (?) SSRI sexual side effects
!  Insomnia (mirtazepine, trazodone)
!  Many similar uses to SSRIs
!  bupropion, mirtazepine, trazodone & nefazodone do
not usually have associated sexual dysfunction

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 26

Atypical antidepressants
!  venlafaxine (Effexor)
"  Similar to TCAs with less safety & side effect concerns
"  FDA approval for depression and generalized anxiety d/
o & social anxiety d/o
"  SNRI- activity depends on dose
"  Minimal DDI
"  SE with missed doses
!  duloxetine (Cymbalta)
"  SNRI profile minimally dose dependent
"  Indicated for depression & chronic neuropathic pain

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Tricyclic antidepressants
!  Mechanism of action
"  Norepinephrine, serotonin, histamine, muscarinic (cholinergic)
and α-adrenergic receptor activity although in differing ratios
"  Anticholinergic activity leads to many of the side effects of
these drugs
!  Indications & off-label uses
"  Depression and similar spectrum of disorders as SSRIs
"  Especially helpful with chronic pain and depression secondary
to medical conditions such as AIDS
"  enuresis, narcolepsy, premature ejaculation, insomnia,
migraine prophylaxis
!  Blood levels: May be obtained to monitor dose effectiveness

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 28

Tricyclic antidepressants
!  Drug-drug interactions (DDI)
"  Multiple significant interactions in each direction with
potentially serious consequences
!  Side effects (SE)
"  Anticholinergic SE include: dry mouth, constipation, blurred
vision and urinary retention
"  Cardiac arrhythmias and conduction changes
"  Orthostatic hypotension
"  Sedation
"  Weight gain
!  Cautions
"  Overdose is frequently fatal
"  Pts with bipolar d/o may be pushed into mania or rapid cycling

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 29

Tricyclic antidepressants
NE 5HT Ach Sed Comments
amitriptyline (Elavil)………low high high high pain, MgrHA
amoxapine (Asendin)…… high low mod low tetracyclic
clomipramine (Anafranil). low high high high tx OCD; SSRI-like
desipramine (Norpramin) high low low low activating
doxepin (Sinequan)……. low low mod high used for insomnia
imipramine (Tofranil)……. low low mod mod pain; enuresis
maprotiline (Ludiomil)…… high low low mod tetracyclic
nortriptyline (Pamelor)….. mod low mod mod chronic pain
protriptyline (Vivactil)…… high low mod low most activating
trimipramine (Surmontil).. low low high high

NE- noropinephrine activity; 5HT- serotonin activity (5-hydroxy-tryptamine); OCD:Obsessive-compulsive d/o

Ach- anticholinergic effects; Sed- sedation; mod-moderate; MgrHA- migraine headache prophylaxis

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 30

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Monoamine Oxidase Inhibitors

SSRI antidepressants
Atypical antidepressants
Tricyclic antidepressants
MAOI
antidepressants
Older mood stabilizers
Newer mood stabilizers
Older antipsychotics
Newer antipsychotics
Anticholinergics
Benzodiazepines
Other anxiolytic/hypnotics
Stimulants
Meds for dementia
Meds for substance abuse
Psychiatric uses of
antihypertensives
Abbreviated as MAOI
1952- First MAOI found with antidepressant
properties in process of looking for an
antituberculosis drug
1962- Investigation of a death from hypertensive
crisis by someone ingesting tyramine rich
food while taking an MAOI
1960’s- Institution of strict dietary restriction of
tyramine containing foods and other
interacting substances.
1960’s- Significant reduction in use due to
introduction of TCAs which do not have
the severe restrictions of MAOIs.
2006- Transdermal selegiline patch (Emsam)
approved to treat depression

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 31

Monoamine Oxidase Inhibitors

!  Features
"  Effective antidepressant for those who can adhere to the
necessary restrictions and tolerate many other side effects
"  Very long duration requiring caution when mixing with
restricted substances or medications
!  Tyramine containing foods (not a complete list)
"  Certain ones may be consumed in moderation
"  Many cheeses, chocolate, soybeans, hot dogs, dry
sausage, caffeine, beer, wine, pickles, olives, … etc.
!  Drug-drug interactions
"  Multiple prescribed and over-the-counter medications can
be potentially lethal. Serotonin syndrome with SSRIs &
many others.

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 32

Monoamine Oxidase Inhibitors

!  Available formulations
"  phenylzine (Nardil);
"  isocarboxazid (Marplan);
"  tranylcypromine (Parnate)
!  Similar medications
"  selegiline (Eldepryl)
!  used to treat Parkinson’s symptoms
!  selective “B” inhibitor at low doses so restrictions not critical
!  at higher doses acts like typical MAOI and so need restrictions
!  recently available as transdermal patch (Emsam) to tx depression
and not needing food restrictions at low dose although still DDI
"  reversible selective “A” inhibitors not available in US (no
restrictions)

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So What’s the Problem?

!  Serotonin Syndrome- unreported in children

and adolescents due to unrecognized
symptoms and lack of research data
!  Problems with serotonin
!  Suicide
!  Psychosis
!  Homicide
!  Physical Illness

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 34

Serotonin Syndrome

!  Serotonin syndrome is most often reported in

patients taking two or more medications that
increase CNS serotonin levels by different
mechanisms. The most common drug combinations
associated with serotonin syndrome involve the
MAOIs, selective serotonin reuptake inhibitors
(SSRIs), and the tricyclic antidepressants. Because
of the dramatic rise in the use of SSRIs, it is
predicted that emergency room physicians are going
to encounter the serotonin syndrome more
frequently than in the past. US Pharmacist Steve Nolan, Pharm.D.

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 35

Serotonin Syndrome Symptoms

!  Mental status changes
Confusion (51%)
Agitation (34%)
Hypomania (21%)
Anxiety (15%)
Coma (29%)
!  Cardiovascular
Sinus tachycardia (36%)
Hypertension (35%)
Hypotension (15%)
!  Gastrointestinal
Nausea (23%)
Diarrhea (8%)
Abdominal pain (4%)
Salivation (2%)

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Serotonin Syndrome Symptoms

!  Motor Abnormalities
Myoclonus (58%)
Hyperreflexia (52%)
Muscle rigidity (51%)
Restlessness (48%)
Tremor (43%)
Ataxia/incoordination (40%)
Shivering (26%)
Nystagmus (15%)
Seizures (12%)
!  Other
Diaphoresis (45%)
Unreactive pupils (20%)
Tachypnea (26%)
Hyperpyrexia (45%)

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 37

Serotonin Syndrome In Children- Deadly

Combinations
!  Antidepressants plus cough and cold
medications-especially medications that
contain antihistamines;
!  Antidepressants plus HT3 Antagonists-
Zofran, Navoban, Kytril, Anzemet, Aloxi;
!  Antidepressants plus psychostimulants;
!  Antidepressants plus alcohol

3/1/16 Dr.Merrill Norton Pharm.D.,D.Ph.,ICCDP-D 38

Serotonin Syndrome-Treatment
!  Pay careful attention to the airway, breathing, circulatory, and neurological parameters. Anticipate airway
compromise due to deterioration of mental status, autonomic instability, and neuromuscular dysfunction.
Secure the airway if gastric lavage and/or charcoal administration are to be performed in the setting of a
decreasing level of consciousness.
!  Gastric lavage is generally not indicated but may be performed within 60 minutes of suspected ingestion
provided the airway is secure.
!  Whole-bowel irrigation may substantially decrease the bioavailability of some ingested drugs; however,
data to support or exclude its use in overdoses causing SS are insufficient.
!  Gastrointestinal decontamination with activated charcoal should be performed with careful attention to
the possibility of impending airway compromise. If progressive deterioration is present, the airway should
be secured via endotracheal intubation prior to any decontamination attempts. Nasogastric tube
placement may facilitate charcoal administration.
!  Two large-bore intravenous catheters should be placed in anticipation of volume and medication
administration. Central venous access is necessary in the patient with progressive cardiovascular
dysfunction. Hydration is of utmost importance because of the risks of rhabdomyolysis and possible
dehydration from increased insensible water losses due to hyperthermia.
!  Rhabdomyolysis should be dealt with quickly, with emphasis on maintaining a high urine output
combined with alkalinization using sodium bicarbonate with a target urine pH of 6.
!  Aggressive cooling may be achieved by removal of clothing, fanning, cooling blankets, spraying with cool
water, and IV fluids.
!  Mechanical ventilation with proper sedation and paralysis with a nondepolarizing muscle relaxant may be
necessary in the setting of life-threatening hyperthermia or rhabdomyolysis.
!  Continuous monitoring of urine output is indicated if the patient requires vigorous fluid resuscitation,
especially in the presence of rhabdomyolysis.
!  Seizures and muscular rigidity are managed best by the use of a benzodiazepine, such as clonazepam or
lorazepam.

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Ques1ons  ??????  

3/1/16   Dr.Merrill  Norton  Pharm.D.,D.Ph.,ICCDP-­‐D   40  

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