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Review of Medication Adherence in Children

and Adults with ADHD

Lisa D. Adler, BA 1 Abstract

Andrew A. Nierenberg, MD 2 Objective: To review the literature on the prevalence, potential causes, and consequences
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1 of medication nonadherence in adult attention-deficit/hyperactivity disorder (ADHD).

Cornell University, Ithaca, NY;
2
Massachusetts General Hospital,
Harvard Medical School, Boston, MA
For personal use only.
Background: Attention-decit/hyperactivity disorder is a common, chronic, and impairing
neuropsychiatric disorder, affecting 4.4% of the US adult population. Medications alleviate
many aspects of the disorder, but associated difculties with disorganization and planning
can lead patients to have poor adherence and subsequent treatment failure. This review will
examine the scope and consequences of medication nonadherence in children and adults with
ADHD. Methods: Comprehensive literature reviews via PubMed searches were conducted
for continuity of medication and medication adherence (and related terms) in ADHD (and
ADD). The studies were reviewed and classied regarding prevalence, measure of adherence
or continuity, etiology, and consequences of medication nonadherence in childhood/adolescent

and adult ADHD. Results: Studies of pharmacy claims databases and treatment studies have
shown that the prevalence of medication discontinuation or nonadherence is between 13.2% to
64%. More studies have focused on medication adherence in children/adolescents than in adult
ADHD. Medication nonadherence is more prevalent in immediate-release versus extended-
release psychostimulants in childhood/adolescent ADHD, but differences in the formulations
have not been studied extensively in adults. Current studies have almost exclusively relied
on patient reports. Possible etiologies of medication nonadherence have not been examined
with formal rating instruments in adult ADHD. The long-term consequences of medication
nonadherence, in terms of impairments, have not been examined. Conclusions: Studies have
documented that medication nonadherence is common in childhood/adolescent ADHD. Further
prospective studies are necessary to document the scope of the problem in adult ADHD and to
examine the potential benets of utilizing extended-release medications in adult ADHD. Stud-
ies correlating the impact of medication nonadherence on symptoms and impairments in adult
ADHD are needed. Future studies should consider utilizing technology to document medication
nonadherence, such as MEMS caps.
Keywords: ADHD; medication adherence; continuity; discontinuity; psychostimulants

Introduction
Attention-decit/hyperactivity disorder (ADHD) is a common and impairing neuro-
psychiatric disorder affecting 6% to 8% of children and 4.4% of the adults.1 Symptoms
Correspondence: Andrew A. Nierenberg,
MD, of ADHD include inattention, impulsivity, distractibility, and excess motor activity.2
Massachusetts General Hospital, Although originally conceptualized as a disorder of childhood, it is now known that
Suite 580,
50 Staniford Street, between one-half and two-thirds of children with ADHD have the disorder persist in
Boston, MA 02114. adulthood.2 Impairments from untreated adult ADHD include decreased academic and
Tel: 617-724-0837
Fax: 617-726-6768 occupational performance, increased rates of marital divorce and separation, increased
E-mail: anierenberg@partners.org motor vehicle accidents, and increased rates of sexually transmitted diseases.3,4

184 Postgraduate Medicine, Volume 122, Issue 1, January 2010, ISSN 0032-5481, e-ISSN 1941-9260
71508e

Adherence is generally dened as the extent to which
a patients actions correspond to the treatment recommen-
dations of health care providers.5 Adherence to treatment
regimens among patients in developed nations averaged
for most common chronic diseases has found to be only
about 50%.5
Estimating the prevalence of medication nonadherence
among adults and children with ADHD is complicated by
how different studies frequently use different denitions of
what constitutes adherence. Some studies will distinguish
adherents from nonadherents by dening a minimal cut-off
point of the percentage of pills taken. Others distinguish
adherents from nonadherents by the number of days each
week the medication was taken as prescribed.
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Previous studies have shown that adherence to psychi-
atric medications among patients with mental illnesses,
like depression, tends to be poor.6 For example, studies of
adherence to antidepressant medications among patients with
depression have found adherence rates of between 40% and
70%.5 Considering the often chronic nature of ADHD and
the serious functional limitations and impairments linked
to untreated adult ADHD, poor adherence to medication
For personal use only.
among adults with ADHD is suspected to be a major barrier
to positive treatment outcomes.7,8 If patients with ADHD fail
to take their medications as prescribed, not only will they
potentially have poor outcomes and continued impairments
in many domains of their lives, but health care providers will
have difculty determining treatment efcacy and assess-
ing the need for medication changes, such as dose titration.
This article reviews the existing literature on the prevalence,
potential causes, and consequences of medication nonadher-
ence in adult ADHD.
Methods
Comprehensive literature reviews via PubMed were con-
ducted for continuity of medication and medication adher-
ence in ADHD and ADD and related terms. Prospective
studies of adherence are generally conducted in a recruited
and screened clinical trial patient population.5 In contrast,
studies of medication continuity are generally retrospec-
tive studies of pharmacy or claims data from Medicaid or
managed care databases in a sample of thousands or hundreds
of thousands of individuals. These claims/pharmacy analysis
studies use continuity that is the amount of time between
the date the rst prescription was lled and the date when
that prescription would run out without further rells, as a
proxy for adherence status.5 The studies were then reviewed
and classied regarding prevalence, measures of adherence
Postgraduate Medicine, Volume 122, Issue 1, January 2010, ISSN 0032-5481, e-ISSN 1941-9260
ADHD Medication Adherence
or continuity of treatment, etiology, and consequences of
medication nonadherence in childhood/adolescent and
adult ADHD. Continuity studies were included only if they
excluded individuals without a diagnosis code for ADHD but
who had pharmacy claims for psychostimulants from their
analyses. Studies reviewed were limited to include only those
containing subjective or objective measures of adherence
or continuity of treatment measured via claims data.
Results
Using these search parameters, 11 studies were identied,
including a total of 7785 adults and 116 559 children and
adolescents (Table 1). Some studies included only child
and/or adolescent participants (n = 8), adults only (n = 2),
or children/adolescents and adults (n = 1). Five studies were
claims analysis studies that measured continuity or duration
of treatment. The size of the 5 claims analyses studies ranged
between 5122 and 40 052 subjects. Six studies examined sub-
jective or objective adherence during a set treatment period.
The adherence studies reviewed here had sample sizes of
between 27 and 407 participants. Of these adherence studies,
3 assessed adherence through parental and/or participant
report alone, 2 assessed adherence through pill count as well
as parental and/or participant report, and 1 study measured
adherence through parental report as well as saliva sample.
Many studies of adherence among children with ADHD
rely on a patient/parental questionnaire to measure adher-
ence as part of a prospective study in which parents and their
children also received behavioral modication therapy on a
weekly basis over the 12-week course of the study.9 Ibrahim9
found in a sample of 51 children that the mean adherence
rate was 74.30% 26.21%. In this study, the author did not
delineate a specic percentage of the medications that had to
be taken for a patient to be considered adherent to the treat-
ment regimen. However, the author stated that he considered
patients who took 70% of their prescribed doses to have
very high adherence.
Charach et al10 studied a subset of 79 children previously
enrolled in a randomized controlled trial of methylphenidate
(MPH) and parent-treatment groups for a follow-up period
of 2 to 5 years. Adherence was measured through inter-
views with the parents and the children, and by pill counts.
Children were categorized as adherent if they took their
medications 5 days a week with no more than 14 weeks
total per year of medication holidays. At year 2, 53% of the
remaining children in the study were adherent; at year 3,
44% were adherent; at year 4, 38% were adherent; and at
year 5, 36% were adherent. The authors found that at year 2,
185
 Lisa D. Adler and Andrew A. Nierenberg
adherents showed a mean improvement on teacher-reported
Ontario Child Health Study Survey Diagnostic Instrument-
Revised (OCHS SDI-R) ADHD symptoms severity scores
from baseline of 9.3 (standard deviation [SD], 8.2), whereas
nonadherents improved by a mean of 2.6 (SD, 8). At year 5,
mean improvement for adherents was 11.5 (SD, 7.3) versus
4.8 (SD, 5.6) for nonadherents.
Marcus et al11 examined continuity of treatment among
children and adolescents treated for ADHD, comparing the
length of treatment among Medicaid beneciaries prescribed
extended-release methylphenidate (ER-MPH) or immediate-
release methylphenidate (IR-MPH). The sample size was
11 537 children and adolescents, of whom 3444 were pre-
scribed ER-MPH and 8093 were prescribed IR-MPH. The
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study found that children and adolescents treated for ADHD
with ER-MPH formulations had a mean duration of treatment
of 140.3 days (95% condence interval [CI], 135.3144.4)
and those treated with IR-MPH had a mean duration of treat-
ment of 103.4 days (95% CI, 101.3103.4). Patients were
dened as discontinuing treatment if there was a gap of 30
days between prescription rells.
Faraone et al12 studied medication adherence to OROS-
For personal use only.
MPH in a 1-year study of 407 children aged 6 to 13 years.
Adherence was assessed via parental report. Children were
classied as adherent if the parental dosing records for
each monthly visit reported that the children were taking
the medication as prescribed 5 days a week except for
planned medication breaks, which were dened as any period
of missed doses that lasted 7 consecutive days. Of the
407 children, 289 (71%) completed the 1-year study. Mean
adherence among the entire study population was 86.4%.
The authors classied children as highly adherent if they
took OROS-MPH as prescribed 75% of the days they
were enrolled in the study. By this denition, 74.7% of the
children were considered to have high adherence. In terms
of outcomes, low adherence was associated with lower
parent ratings of treatment efcacy at the end of the study
(P = 0.01) but not with lower teacher ratings of treatment
efcacy (P = 0.81).
In a claims analysis by Winterstein et al,13 of 40 052 children
and adolescents between the ages of 5 and 20 years newly
diagnosed with ADHD and initiating medication treatment for
the rst time, 49.4% (95% CI, 49.450.5) remained on their
medications after 1 year of treatment, allowing for a 3-month
gap in treatment.13 Again allowing for up to a 3-month break in
treatment, 32.8% (95% CI, 32.233.4) of the sample persisted
with treatment 2 years after beginning and 17.2% (95% CI,
16.418) persisting with treatment for 5 years. Allowing for
186 Postgraduate Medicine, Volume 122, Issue 1, January 2010, ISSN 0032-5481, e-ISSN 1941-9260
only a 1-month gap in treatment, 26.9% (95% CI, 32.233.4)
of this population continued to take their medication after
1 year of treatment.
Pappadopulos et al14 conducted a retrospective comparison
of adherence rates measured through parental report to adher-
ence measured through physiological measures of adherence
(a saliva assay) from data collected during the 14-month
National Institute of Mental Health Collaborative Multisite
Multimodal Treatment Study of Children with Attention-
Decit Hyperactivity Disorder (MTA).14 The 254 children
in the MTA study had all received a diagnosis of ADHD
combined type and were aged 7 to 9.9 years. The MTA
study examined 4 cohorts of children with ADHD who were
followed longitudinally: community pharmacological treat-
ment alone, intensive psychopharmacologic treatment with
IR-MPH, psychosocial treatment alone, and a combination
of psychosocial and intensive psychopharmacological treat-
ment with IR-MPH. Verbal and physiological adherence data
were only collected for the medication management-alone
group (medical management) and the combined-treatment
group (combined).
Participants in this study were characterized as verbal
adherents if the parent(s) reported that their child took 50%
of their prescribed doses each month at 80% of the monthly
visits. For the children to be classied as physiologically
adherent, 50% of their saliva assays had to contain a detect-
able level of MPH. The authors reported that 96.9% of the
subjects met the criteria for verbal adherence.14
The authors note that not all of the children in the study
had the same number of saliva samples taken; the mean
number of usable assays was 2.9 assays per participants. Of
the total 748 saliva samples taken over the course of the study,
23.5% were classied as physiologically nonadherent, indi-
cating that no MPH had been taken within the past 8 hours.
Whereas parental report classied 3.1% of the children as
nonadherent, by saliva assay measures, 24.8% of the children
were classied as nonadherent. Furthermore, while 89.4%
of children were classied as perfect (100%) adherents by
parental report measures, only 53.5% of the children were
physiologically adherent in all their saliva assays. The authors
stated that there was no signicant difference in physiological
adherence between the medical management and combined
groups. At 14 months, children who were physiologically
nonadherent in the medical management group had a compos-
ite parent-teacher SNAP score of 1.20 from a baseline score
of 2.11; physiological nonadherents in the combined group
had a score of 0.93 and a baseline score of 1.88. Physiologi-
cal adherents in the medical management group had a nal
 ADHD Medication Adherence

Table 1. Studies of Adherence

Study N Age (SD) Design Adherence/ Adherence/ Results Comments
Years Continuity Continuity
Measure(s) Definitions
Child Studies
Ibrahim9 51 Range, 716.6 Referred sample Parental and Adherence via pill Mean Parents and children
(2002) treated for self-report count not defined adherence rate: received concurrent
ADHD and pill counts 76.1% 27.11% behavioral modifica-
(adherence) (week 1), tion therapy sessions
74.3% 26.61% which may have
(3 months) improved adherence.
Small sample. Adher-
ence not defined.
Charach et al10 79 Mean 8.4 (1.6); 25 year Pill counts, paren- Discount planned Year 2: 53% Sample size
(2004) range, 612 follow-up of tal and participant medication holiday adherent; year decreased by year 5.
MPH study reports of up to 14 weeks 3: 44% adherent; Adherence
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(adherence) total year 4: 38% decreased over time.

adherent; year
5: 36% adherent
Marcus et al11 11,537 Range, 617 Children who Claims analysis: Discontinuity: ER-MPH: mean Continuity greater
(2005) started ER Medicaid 30-day lapse in continuity with ER-MPH.
or IR-MPH (continuity) prescription supply 140.3 days,
treatment IR-MPH: mean
continuity
103.4 days
Faraone et al12 407 Mean, 9.2 (1.8); Children in Parental report Adherent: taking Mean Fairly good adher-
For personal use only.

(2007) range, 613 1 year open (adherence) medication adherence rate ence with open ER
label OROS 5 days/week. 86.4%; 75% OROS MPH; adher-
MPH study Exempted medica- showed high ence measured after
tion holidays adherence short duration of
( 75% days on treatment. Monthly
medication) contact with inves-
tigators may have
increased adherence.
Study not designed
specifically to mea-
sure adherence.
Winterstein 40,052 Range, 520 ADHD cohort Claims analysis Discontinuous: 3-month gap, Continuity rates
et al13 (2008) identified out (continuity) 1- or 3-month % continued decrease substan-
of 2 131 953 gap between drug (time elapsed): tially over time.
Medicaid claims 49.9% (1 year),
beneficiaries 32.8% (2 years),
17.2% ( 5 years),
15.4% (9 years);
1 month gap
26.9% (1 year)
Pappadopulos 254 Mean, 7.8 (0.8); 14-month Parental report, Parental report: Saliva: 24.8% Only 10.3% of
et al14 (2009) range, 7.09.9 follow-up marker saliva assay 50% compliance nonadherent; physiological
of MTA study (adherence) at 80% of monthly parental report: nonadherence
visits; saliva assay: 3.1% of children cases identified by
50% samples nonadherent parental report.
with detectable Physiological mea-
MPH levels sures may better
detect nonadher-
ence than parental
or patient report.

(Continued)

Postgraduate Medicine, Volume 122, Issue 1, January 2010, ISSN 0032-5481, e-ISSN 1941-9260 187
 Lisa D. Adler and Andrew A. Nierenberg

Table 1. (Continued)
Study N Age (SD) Design Adherence/ Adherence/ Results Comments
Years Continuity Continuity
Measure(s) Definitions
Olfson et al15 9559 (OROS- Range, 612 Claims analyses in Claims analysis Discontinuous: gap Mean stimulant Mean duration
(2009) MPH: 3815; dosing analyses of (continuity) of 30 days in episode (days): of treatment
IR-MPH: children treated claims; examined 160.8 32.3 relatively short
1960; MAS with MPH duration of OROS MPH, (circa 1/2 year). ER
XR: 1847; IR- treatment 145.4 37.5 duration did not
MAS: 1937) IR-MPH, substantially differ
158.0 36.2 from IR.
MAS XR,
150.8 36.2
IR-MPH
Chou et al16 137 Mean, 10.4 Children who Parental report Poor adherence: 72.3% of those Possible sample
(2009) (2.6) were poorly (adherence) missed 1 dose poor adherents selection bias in
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adherent to on 2 school to IR-MPH patients choosing to

IR-MPH: 103 days/week for switched to remain on IR-MPH
continued on 3 weeks or parent/ ER-MPH became who were nonad-
IR-MPH, 137 participant report adherent herent. Adherence
switched to same/worse adher- used combined
OROS ER-MPH ence compared measures of days
with IR and parental global
report of adherence.
Perwien et al17 11 962 Mean children, Pharmacy man- Claims analysis Compliance = Mean days com- MPR assumes
(2004) children and 9.9 (3.5); mean aged care data on patients with MPR 0.80, pliant: children patients actually take
2636 adults adults, 35.2 base analyses on diagnosis code Persistence = MPR 34.2 (75.6) SD; all refills. Compliance
For personal use only.

(10.6) patients treated and treatment 0.30 adults 49.5 rates low. Not true
for ADHD (continuity) (109.0); Mean measure of adher-
days persistent: ence as claims
children 209 analyses. Large vari-
(204.5); adults ability of compliance
199.9 (219.9) and persistence. All
patients had newly
diagnosed ADHD.
Adult Studies
Safren et al8 27 Mean, 42.14 Previous Self-report Adherence = Mean adherence Small sample size.
(2007) (10.5) participants in a questionnaire 80% doses rate: 86.8%, 22% Patients not all on
trial comparing (adherence) taken over nonadherent, same medications.
CBT + mainte- 2 weeks 26% reported
nance medication 100% adherence.
with maintenance ADHD medica-
medication alone tion adherence
negatively
correlated with
measures of
ADHD symp-
tom severity.
Olfson et al15 5122 (2833 ER-MPH: mean, Managed care Claims analysis: Discontinuity: IR-MPH: 39.0 day Treatment duration
(2007) ER-MPH, 31.2 (12.4); sample pre- pharmacy 30 days median treat- longer with ER-MPH.
2289 IR- IR-MPH: mean, scribed either and medical between end of ment duration,
MPH) 33.3 (12.2) ER-MPH or (continuity) days supplied on ER-MPH 68-day
IR-MPH last claim and date median duration.
of next claim % with 2
pharmacy claims:
50.5% (IR-MPH),
61.4% (ER-MPH).
Abbreviations: ADHD, attention-deficit/hyperactivity disorder; CBT, cognitive behavioral therapy; ER-MPH, extended-release methylphenidate; IR-MPH, immediate-release
methylphenidate; MAS XR, mixed amphetamine salts extended release; MPR, medication possession ratio.

188 Postgraduate Medicine, Volume 122, Issue 1, January 2010, ISSN 0032-5481, e-ISSN 1941-9260

score of 0.88 and baseline of 2.05; physiological adherents
in the combined group had a nal score of 0.90 and baseline
of 2.07. The greatest difference in nal symptom scores then
were between nonadherents in the medical management
group in comparison with all other groups.
In a claims analysis of 9559 children aged 6 to 12 years
prescribed either MPH or mixed amphetamine salts (MAS) in
either ER or IR formulations, Olfson et al15 found relatively
short mean durations of treatment regardless of medication
taken, but longer mean durations of treatment for those
subjects taking extended-release medications OROS-MPH
or mixed amphetamine salts extended release (MAS XR)
in comparison with their immediate-release counterparts.15
Subjects were classied as discontinuing treatment if a gap
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of 30 days existed between claims. Subjects prescribed
OROS-MPH had mean continuity of 160.8 32.3 days;
145.4 37.5 days for IR-MPH; 158.0 36.2 days for
MAS XR; and 150.8 36.2 days for IR MAS.
Chou et al16 examined adherence and treatment outcome
among 137 children with ADHD who were newly prescribed
OROS MPH. These children were switched to OROS MPH
because they were identied by their physicians as poor
For personal use only.
adherents to IR MPH. The average frequency of dosing the
children received while they were prescribed IR-MPH is
unknown. Children were classied as nonadherent to OROS
MPH if parent(s) reported that medication was not taken
2 days per school week during the 3-week treatment period
or if the parents reported same or worse adherence to OROS
MPH in comparison with IR-MPH. The study classied
72.3% of its subjects as adherent to OROS MPH. Conrm-
ing claims analyses studies suggesting short durations of
treatment in community care, poor adherents to OROS-MPH
discontinued after a mean of 9.6 weeks (SD, 10.7) of treat-
ment but good adherents to OROS-MPH discontinued after
a mean of only 15.1 weeks (SD, 18.7). The authors did not
analyze the data to determine correlations between adherence
to OROS MPH and symptom improvement.
In a claims analysis by Perwien et al,17 of 11 962 children
and 2636 adults newly diagnosed with ADHD and newly
prescribed medication for ADHD within the past 6 months,
the authors found continuity and adherence measures were
similarly poor among children and adults. Claims data
gathered from an 18-month period among patients enrolled
in several HMOs were studied retrospectively. The authors
used medication-possession ratio measures (MPR) to esti-
mate continuity, which the authors called persistence
and adherence, which the authors called compliance.
The authors dened persistence as an MPR 0.30 and
Postgraduate Medicine, Volume 122, Issue 1, January 2010, ISSN 0032-5481, e-ISSN 1941-9260
ADHD Medication Adherence
compliance as an MPR 0.8. Children were compliant for
a mean of 34.2 days (SD, 75.6) and adults for a mean of
49.5 days (SD, 109). Children were persistent for a mean of
209 days (SD, 204.5) and adults for a mean of 199.9 days
(SD, 219.9). The range for both compliance and persistence
was 0 to 547 days (the authors only analyzed data gathered
from a 547-daytime period). The longer mean compliance
measure and greater SD among adults in the study suggest
that some subjects were included who were compliant with
their medications for a much longer period of time than the
majority of individuals in the adult sample. However, the
mean length of time patients were compliant was 2 months
for both children and adults and both children and adults were
on average persistent for 1 year.
Two studies were found via the search parameters that
exclusively measured adherence or continuity in adult
populations.8,18 Safren et al8 studied adherence to medication
among 27 adults treated with a variety of medications for
ADHD, all of whom had previously participated in a trial
comparing cognitive behavioral therapy (CBT) and pharma-
cotherapy to pharmacotherapy alone. The authors reported a
mean adherence rate of 86.8% (SD, 14.5%) during the 2-week
assessment period.8 The authors dened optimal adherence
as reporting taking 80% of prescribed medication. Adher-
ence was assessed through patient questionnaire to determine
medication adherence during the 2-week period prior to the
study visit. In this study, only 22% of participants reported
80% adherence. The authors found that the average adher-
ence rate in the study population was 86%. The authors did
not report if there was a difference in adherence rates from
the study sample among those who in the previous study
had received CBT in addition to maintenance pharmacology
in comparison to those who received pharmacology alone.
Olfson et al18 examined continuity of MPH treatment
among an adult ADHD population using claims analysis of
5122 (2289 IR-MPH and 2833 ER-MPH) individuals newly
treated for ADHD.18 Continuity was assessed by duration of
the treatment episode. The authors dened discontinuation
of treatment by the time beyond which the individual should
have no medication left to take and failed to rell or to occur
at any point where their was a gap of 30 days between pre-
scription rells. They found that patients prescribed IR-MPH
had an overall median treatment continuity of 39 days
(95% CI, 3352), and those prescribed ER-MPH had an over-
all median treatment continuity of 68 days (95% CI, 6571).
The authors also reported that only 50.5% of those prescribed
IR-MPH and 61.4% of those prescribed ER-MPH had 2 or
more stimulant pharmacy claims. Among those with more
189
 Lisa D. Adler and Andrew A. Nierenberg
than 2 stimulant pharmacy claims, the median continuity of
treatment was 121 days (95% CI, 113130) among those
prescribed IR-MPH and 138 days (95% CI, 130149) among
those prescribed ER-MPH.
Discussion
The results of this literature review on medication adher-
ence and continuity in adult ADHD suggests that further
studies are necessary to document the magnitude of the
problem of nonadherence and early discontinuity of treat-
ment. In clinical trial populations of both children and
adults, mean nonadherence rates of between 13.2% and
64% were found.810,12,14,16 The highest rate of medication
nonadherence (64%) was found 5 years after treatment
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began, suggesting that nonadherence and discontinuity
increases when patients are followed for longer periods
of time.10 Claims studies using naturalistic samples have
all found mean continuities of 1 year, and usually 6
months.11,13,15,17,18 This suggests that studies based on a popu-
lation in community treatment tend to show higher rates of
discontinuation at shorter periods of time than are reected
in adherence measures conducted in treatment studies.
For personal use only.
True measures of adherence may be even lower than those
approximated by pharmacy claims studies, which measure
continuity, because these studies did not document if the
individuals consistently took the medications for which
they relled prescriptions.
Despite the paucity of existing literature on adherence
and continuity among adults with ADHD, the literature on
adherence among children and adolescents with ADHD
suggests that for both children and adults, adherence is
probably higher in controlled study populations than in
community care populations of adults.8,17 Therefore, future
studies could examine if increased support and monitoring
of patients receiving pharmacological treatment for ADHD
in community settings could increase adherence.
Complicating cross-study comparisons, many of the
studies discussed here used different denitions of adherence
or continuity. Among adherence studies, one did not specify
a percentage of medications that had to be taken to classify
a patient as adherent9 and several used percentage cut-offs
of 75%, 50%, or 80%, respectively.12,14,8 Thus, patients who
might have been considered adherent in one study might not
have been considered adherent in another study.
Although most of the adherence studies reviewed here
utilized self-report measures of adherence, Pappadopulos
et al14 demonstrated that parental/participant self-report can
potentially be an inaccurate measure of adherence status.
190 Postgraduate Medicine, Volume 122, Issue 1, January 2010, ISSN 0032-5481, e-ISSN 1941-9260
Future studies should consider utilizing technology to
document medication nonadherence like MEMS caps, which
record when and what time medication bottles are opened.
Potential issues with MEMS cap technology include that
patients may have difculty opening bottles, or taking the
bottles with them during their day, or that the technology
could be more expensive than administering questionnaires
to assess adherence.5
Some studies, both in child and in adult populations,
suggest that ER-MPH formulations may increase adher-
ence and lengthen treatment durations in comparison with
IR-MPH.11,12,15,16 However, the major study to date directly
comparing adherence to an ER-MPH formulation with adher-
ence to IR-MPH, had a sample bias in that all of the children
participants were selected because they had previously been
poor adherents to IR-MPH.16 While several claims analysis
studies of child and adolescent populations showed longer
mean duration of treatment among individuals prescribed
ER-MPH medications than those prescribed IR-MPH, mean
durations of treatment with both ER-MPH formulations and
IR-MPH was 6 months.11,15 Further study is needed to
document if ER-MPH formulations increase adherence and
treatment duration in adults with ADHD and what effect
they have on long-term treatment outcomes in comparison
with IR-MPH.
Adherence to medications for patients with ADHD may
be complicated by the disorders related executive function
decits that make remembering to take time-action medica-
tions, such as psychostimulants, more difcult for many
individuals.8 Studies correlating the impact of medication
adherence on symptoms and impairment in adult ADHD
are necessary. Studies that have examined the relationship
between adherence and outcome measures in adolescents and
children have found that ratings of treatment efcacy from
parents or teachers12 or symptom reduction from parents or
teachers positively correlate with adherence status.10 Future
studies might want to examine relationships between adher-
ence status in adults and self-report of treatment efcacy
or self-report improved self-function at work/school, at
home, and in familial or social relationships, domains in
which documented impairments have been found to exist in
untreated adult ADHD.3,4
Future research is necessary to determine what barriers in
real-world settings hinder adherence and to test interventions
that might improve medication adherence and continuity of
treatment, such as peer support groups, or devices to remind
patients when to take their medication. An interesting area for
potential research could focus on integrating measurement,

management, and shared decision making19 between patients
with adult ADHD and their health care providers, and the
impact on adherence and treatment outcomes.
Acknowledgments
This article was presented in November 2009 as part of
a poster at the American Professional Society of ADHD
and Related Disorders (APSARD) Annual Meeting in
Philadelphia, PA.
Conflict of Interest Statement
Lisa D. Adler, BA discloses no conflicts of interest.
Andrew A. Nierenberg, MD discloses conicts of inter-
est with the American Psychiatric Association, Appliance
Postgraduate Medicine Downloaded from informahealthcare.com by RMIT University on 08/11/15
Computing Inc. (Mindsite), Brain Cells, Inc., Brandeis
University, Eli Lilly and Company, Novartis, PGx Health,
Shire, Schering-Plough, Targacept, and Takeda Pharma-
ceuticals. He received grant/research support through MGH
from NIMH, PamLabs, Pzer Pharmaceuticals, and Shire.
He received honoraria from Belvoir Publishing, University
of Texas Southwestern Dallas, Hillside Hospital, American
Drug Utilization Review, American Society for Clinical
For personal use only.
Psychopharmacology, Baystate Medical Center, Columbia
University, Imedex, MJ Consulting, New York State, MBL
Publishing, Physicians Postgraduate Press, SUNY Buf-
falo, University of Wisconsin, and the University of Pisa.
Dr. Nierenberg is a presenter for the Massachusetts General
Hospital Psychiatry Academy (MGHPA). The education
programs conducted by the MGHPA were supported through
Independent Medical Education (IME) grants from the fol-
lowing pharmaceutical companies in 2008: Astra Zeneca, Eli
Lilly, and Janssen Pharmaceuticals; in 2009 Astra Zeneca,
Eli Lilly, and Bristol-Myers Squibb. Dr. Nierenberg owns
stock options in Appliance Computing, Inc. and Brain Cells,
Inc. Through MGH, he is named for copyrights to the Clini-
cal Positive Affect Scale and the MGH Structured Clinical
Interview for the Montgomery Asberg Depression Scale
exclusively licensed to the MGH Clinical Trials Network
and Institute (CTNI). Also, through MGH, Dr. Nierenberg
has a patent extension application for the combination of
buspirone, bupropion, and melatonin for the treatment of
depression.
Postgraduate Medicine, Volume 122, Issue 1, January 2010, ISSN 0032-5481, e-ISSN 1941-9260
ADHD Medication Adherence
References
1. Kessler RC, Adler LA, Barkley R, et al. The prevalence and correlates of
adult ADHD in the United States: results from the National Comorbidity
Survey Replication. Am J Psychiatry. 2006;163(4):716723.
2. Adler LA, Cohen J. Diagnosis and evaluation of adults with attention-
decit/hyperactivity disorder. Psychiatr Clin N Am. 2004;27:187201.
3. Adler LA, Chua HC. Management of ADHD in adults. J Clin Psychiatry.
2002;63(suppl 12):2935.
4. Barkley RA. Attention-Decit Hyperactivity Disorder: A Handbook for
Diagnosis and Treatment. New York, NY: Guilford Press; 1998.
5. World Health Organization. Adherence to long-term therapies: evidence
for action. Geneva, Switzerland; 2003:18.
6. Cantrell CR, Eaddy MT, Shah MB, Regan TS, Sokol MC. Methods
for evaluating patient adherence to antidepressant therapy: a real-
world comparison of adherence and economic outcomes. Med Care.
2006;44(4):300303.
7. Sanchez RJ, Crismon ML, Barner JC, Bettinger T, Wilson JP. Assess-
ment of adherence measures with different stimulants among children
and adolescents. Pharmacotherapy. 2005;25(7):909917.
8. Safren SA, Duran P, Yovel I, Perlman CA, Sprich S. Medication adher-
ence in psychopharmacologically treated adults with ADHD. J Atten
Disord. 2007;10(3):257260.
9. Ibrahim el SR. Rates of adherence to pharmacological treatment among
children and adolescents with attention decit hyperactivity disorder.
Hum Psychopharmocol. 2002;17(5):225231.
10. Charach A, Ickowicz A, Schachar R. Stimulant treatment over ve years:
adherence, effectiveness, and adverse effects. J Am Acad Child Adolesc
Psychiatry. 2004;43(5):559567.
11. Marcus SC, Wan GJ, Kemner JE, Olfson M. Continuity of methylpheni-
date treatment for attention-decit/ hyperactivity disorder. Arch Pediatr
Adolesc Med. 2005;159(6):572578.
12. Faraone SV, Biederman J, Zimmerman B. An analysis of patient
adherence to treatment during a 1-year, open-label study of OROS-
methylphenidate in children with ADHD. J Atten Disord. 2007;11(2):
6473.
13. Winterstein AG, Gerhard T, Shuster J, et al. Utilization of pharmaco-
logic treatment in youth with attention decit/hyperactivity disorder
in Medicaid database. Ann Pharmacother. 2008;42(1):2431.
14. Pappadopulos E, Jensen PS, Chait AR, et al. Medication adherence
in the MTA: saliva methylphenidate samples versus parent report and
mediating effect of concomitant behavioral treatment. J Am Acad Child
Adolesc Psychiatry. 2009;48(5):501510.
15. Olfson M, Marcus S, Wan G. Stimulant dosing for children with ADHD:
a medical claims analysis. J Am Acad Child Psychiatry. 2009;48(1):
5159.
16. Chou WJ, Chou MC, Tzang RF, et al. Better efcacy for the osmotic
release oral system methylphenidate among poor adherents to
immediate-release methylphenidate in the three ADHD subtypes.
Psychiatry Clin Neurosci. 2009;63(2):167175.
17. Perwien AR, Hall J, Swensen A, Swindle R. Stimulant treatment
patterns and compliance in children and adults with newly treated
attention-dect/hyperactivity disorder. J Manag Care Pharm. 2004;10(2):
122129.
18. Olfson M, Marcus SC, Zhang HF, Wan GJ. Continuity of methylphe-
nidate treatment of adults with attention-decit/hyperactivity disorder.
J Manag Care Pharm. 2007;13(7):570577.
19. Nierenberg AA, Ostacher MJ, Borrelli DJ, et al. The integration of
measurement and management for the treatment of bipolar disorder:
a STEP-BD model of collaborative care in psychiatry. J Clin Psychiatry.
2006;67(suppl 11):37.
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