JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY

Volume XX, Number XX, 2019

ª Mary Ann Liebert, Inc.
Pp. 1–21
DOI: 10.1089/cap.2018.0153

A Review of Factors Influencing the Three Phases

of Medication Adherence in People
with Attention-Deficit/Hyperactivity Disorder

Muhammad Umair Khan, MPhil, and Parisa Aslani, PhD

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Abstract
Objectives: Factors affecting adherence to medications in people with attention-deficit/hyperactivity disorder (ADHD) are
not well understood in the context of their influence on the different phases of adherence, that is, initiation, implementation,
and discontinuation. This review aimed to identify the factors affecting the three phases of medication adherence in people
with ADHD.
Methods: Six electronic databases, including Medline, PubMed, IPA, CINAHL, Embase, and PsycINFO, were systemati-
cally searched from inception through October 2018 with the limitations of English language and human studies. The search
strategy was based on three concepts (adherence, ADHD, and factors) and their relevant terminologies.
Results: Considerable variability was observed with regards to the criteria used to define adherence in identified studies
(n = 48). Most studies focused on the implementation phase of adherence (n = 27), while only a handful focused on the
initiation (n = 6) and discontinuation (n = 5) phase of adherence. The remaining studies (n = 10) examined multiple phases of
adherence. Conflicting information received about medication, medication frequency, and fears of medication’s effect on
growth were the unique factors impacting initiation, implementation, and discontinuation, respectively. Moreover, factors
within each phase of adherence also differed with different populations such as parents, children, adolescents, and adults. Fear
of addiction, medication effectiveness, psychiatric comorbidity, and medication side effects were the most common factors
identified in all three phases of adherence.
Conclusions: This review found some unique factors in each phase of adherence while some overlap was also noted. Future
interventions to improve adherence should be phase- and group specific rather than consider adherence as a single variable.

Keywords: initiation, implementation, discontinuation, persistence, ADHD

Introduction The use of pharmacological agents is considered an integral

component of evidence-based management in people with ADHD.

A ttention-deficit/hyperactivity disorder (ADHD) is one of

the most common psychiatric disorders among children and ad-
olescents, characterized by hyperactivity, inattention, and impulsivity
(Winterstein et al. 2008). ADHD is a chronic condition that often
continues to demonstrate notable symptoms throughout life. Polanczyk
et al. (2007) estimated the worldwide prevalence of ADHD as 5.29% in
children aged 18 years or younger. In another review, Willcutt et al.
(2012) estimated the global prevalence of ADHD as 5.9%–7.1% in
children and adolescents. In 2014, Polanczyk et al. updated their pre-
vious review and reported the global prevalence as about 5% (Polanczyk
et al. 2014). The variation in estimated prevalence of ADHD was best
explained by the methodological heterogeneity between the studies
(Sayal et al. 2018). The worldwide prevalence of ADHD has been
reported as 1.2% to 7.3% in adults (Polanczyk et al. 2007).
Stimulant medications, such as methylphenidate (immediate re-
lease, modified release, and osmotic controlled release) and am-
phetamines, are the first-line pharmacological agents for the
management of ADHD. Nonstimulants, such as atomoxetine,
guanfacine, and clonidine, are usually considered as the second-
line options (National Institute for Health and Care Excellence
2018).
Despite the availability of effective behavioral treatment, phar-
macotherapy plays a primary role in the management of ADHD
(Dopheide 2009). The use of pharmacotherapy has been supported
by robust efficacy and safety data (Murray et al. 2008). Further-
more, the use of medication is considered the most cost-effective
therapy for ADHD (National Institute for Health and Care Ex-
cellence 2018). This is particularly important owing to the chronic

Faculty of Medicine and Health, The University of Sydney School of Pharmacy, The University of Sydney, Camperdown, Australia.
Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

1
 2 KHAN AND ASLANI
nature of the disease as it allows the use of long-term pharmaco-
therapy. It has been reported that the use of long-term medications
results in improved academic and social functioning of people with
ADHD (Wilens et al. 2008; Chien et al. 2012). The use of phar-
macotherapy among children with ADHD has increased substan-
tially in the past 2 decades (Raman et al. 2018). Even in adults,
where ADHD is relatively less prevalent and diagnosed, the use of
medication has increased by 18% (Dopheide 2009). A study re-
ported that the use of methylphenidate has increased from 39.6% in
1997 to 54% in 2005 in Taiwan (Chien et al. 2012). Another study
from Germany reported that 52% of patients were prescribed
pharmacological agents as part of ADHD treatment (Garbe et al.
2012). Furthermore, a recent study suggested a 101.8% increase in
the use of ADHD medications in Australia from 2007 to 2015 (Brett
et al. 2017).
Adherence to ADHD medication is very important to achieve
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the desired treatment outcomes. However, it has been reported
that poor medication adherence is common among people with
ADHD and leads to suboptimal therapeutic response. A sys-
tematic review of 12 studies measuring adherence in children
and adolescents reported a range of 9.8% to 64% (Gajria et al.
2014). The wide variation in the reported rate of adherence
could be explained by the use of different terminologies and
taxonomies in the adherence-related literature. Medication ad-
herence comes under the broader concept of medication-taking
behavior, the history of which is as old as the time of Hippo-
crates (Osterberg and Blaschke 2005). However, in the late 20th
century, the concept was given the term ‘‘compliance’’ (Haynes
1979). Compliance was defined as ‘‘the extent to which the
patient’s behavior (in terms of taking medications, following
diets, or executing other lifestyle changes) coincides with
medical or health advice’’ (Haynes 1979). However, as the
concept of patient-centered care evolved, the term ‘‘compli-
ance’’ received criticism because it was viewed as implying
passive acceptance of clinician’s recommendation by the pa-
tient. This led to the introduction of the term ‘‘adherence’’ that
gives patients a more active role in disease management. Ad-
herence was defined as ‘‘The extent to which a person’s be-
haviour- taking medication, following a diet, and/or executing
lifestyle changes, corresponds with agreed recommendations
from a health care provider’’ (World Health Organization
2003). These terms have been used interchangeably in the lit-
erature and have generated confusion and inconsistencies in
adherence research (Ahmed and Aslani 2014).
Several studies have reported mean adherence of <6 months, and
occasionally <1 year, using naturalistic samples (Adler and Nier-
enberg 2010). Furthermore, a cohort of patients using methylphe-
nidate reported using prescribed medication only half of the time
recommended by their clinician (Darredeau et al. 2007). It has also
been reported that the rate of adherence in people with ADHD is
low regardless of the pharmacological treatment options (i.e.,
stimulant or nonstimulant) (Treuer et al. 2016). A study reported
medication discontinuation rate of 13.2% to 64% among people
with ADHD (Adler and Nierenberg 2010). The low level of ad-
herence to ADHD medications results in symptomatic relapse, in-
creased morbidity, increased health expenditure, and difficulties for
the clinician to assess the effectiveness of the prescribed regimen
(Ahmed and Aslani 2013). Nonadherence has also been associated
with suboptimal response and less improvement in clinical severity
(Childress and Sallee 2014). The success of transition from initial
management to long-term treatment is fraught with pitfalls. Lack of
adherence to the prescribed regimen is believed to be the barrier
toward successful long-term management of ADHD (Skoglund
et al. 2016).
In view of the poor medication adherence in people with
ADHD, it is essential to examine the factors contributing to
nonadherence. Lack of information about the determinants of
medication adherence can pose a critical challenge to clinicians.
The reasons for nonadherence to ADHD medications are multi-
factorial and difficult to examine (Adler and Nierenberg 2010).
There has been a recent surge in studies examining the factors
associated with medication adherence in people with ADHD
(Skoglund et al. 2016). Some studies have reported demographic
factors such as socioeconomic status, age, gender, geographic
location, race, ethnicity, and clinical characteristics as the major
barriers to adherence (Winterstein et al. 2008; Chen et al. 2009;
Coker et al. 2016). Other studies have shown the lack of treatment
effectiveness, parental will, and social factors as the main con-
tributors toward nonadherence in people with ADHD (Antony
2016). Parental beliefs and attitudes about ADHD medication
have also found to be contributory factors toward ADHD medi-
cation adherence (Dosreis and Myers 2008). Health care associ-
ated costs such as the cost of prescriptions and other indirect costs
such as time off from work and providing care for a person with
special needs may also affect adherence to medication use in some
settings (Fiks et al. 2012).
Few attempts have been made to summarize the factors affecting
adherence to medications in people with ADHD. Some reviews
have reported the factors associated with discontinuation only
(Gajria et al. 2014; Frank et al. 2015), while others have focused on
specific medications such as atomoxetine (Treuer et al. 2016). One
systematic review distinguished the factors as patient related or
medication related (Caisley and Müller 2012), while others nar-
rated the factors without any categorization (Swanson 2003;
Charach and Gajaria 2008; Greydanus and Kaplan 2012; Childress
and Sallee 2014). No attempt has been made to review the existing
body of research to identify and classify the factors affecting
medication adherence in the context of its three phases, that is,
initiation, implementation, and discontinuation. Research in other
disease populations suggests that factors influencing one phase of
adherence may not necessarily affect the other two phases (Gille-
spie et al. 2017; Srimongkon et al. 2018). Therefore, it is important
to classify factors based on the three phases so that phase-specific
interventions could be developed to improve medication adher-
ence. This concept was initially proposed by Vrijens et al. (2012)
who recommended a more rigorous taxonomy (the ABC taxonomy)
of adherence to better understand the complex issue of medication
adherence in clinical settings.
The ABC taxonomy defines medication adherence as the process
by which patients take their medications as prescribed (Vrijens
et al. 2012). In this taxonomy, adherence to medication was clas-
sified into three phases: initiation, implementation, and discontin-
uation. The three phases of adherence are underpinned by the
assumption that the patient/parent/carer has agreed with the treat-
ment. Initiation was defined as commencement of the prescribed
medication. Implementation was defined as the extent to which
patients follow their prescribed regimen from initiation until dis-
continuation. Discontinuation was defined as an earlier than pre-
scribed end of therapy by the patient for any given reason (Vrijens
et al. 2012). The aim of this review was to identify the factors
affecting adherence at initiation, implementation, and discontinu-
ation phases of adherence (ABC taxonomy) and differentiate the
factors affecting adherence to ADHD medications in children,
adolescents, adults, and parents/carers based on the three phases.
 FACTORS INFLUENCING ADHERENCE TO ADHD MEDICATION
Methods
Data sources and search strategy
The following six electronic databases were searched: Medline,
PubMed, International Pharmaceutical Abstracts (IPA), Cumulative
Index to Nursing and Allied Health Literature (CINAHL), Embase, and
the Psychological Information Database (PsycINFO). A systematic
search was performed for all studies that examined factors affecting
medication adherence or its related terms (compliance and persistence)
in people with ADHD. All databases were searched from inception
through October 2018 with the limitations of English language and
human studies. The search strategy combined terms that represented
adherence, ADHD, and factors (Supplementary Table S1).
Eligibility criteria
The eligibility criteria were developed to include all studies that
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examine the factors influencing medication adherence regardless of any
minimum or maximum requirement for study duration, number of pa-
tients, number of medication, doses, frequency, and type of medication.
Moreover, studies were not included/excluded based on the definition of
adherence. The broad approach was chosen to accommodate the
methodological and taxonomical heterogeneity in the adherence liter-
ature. The following inclusion/exclusion criteria were set for the studies.
Inclusion criteria
Studies that:
 examined factors affecting adherence or its related terms to
at least one type of medication used for people with ADHD;
 included details of what phase(s) of adherence was measured
or at what stage of medication-taking the factors were
evaluated to allow categorization of the factors based on the
three phases of adherence;
 included children, adolescents, adults, or parents/carer as
study participants.
Exclusion criteria
Studies were excluded if they:
 examined adherence to nonpharmacological management of
ADHD;
 measured adherence but did not evaluate the factors affecting
medication adherence;
 compared the level of adherence between two medications
but did not focus on examining factors affecting adherence;
 were reviews, commentaries, conference abstracts, and ex-
pert opinions.
Study selection
The articles were selected after a thorough two-phase review
process. In the first phase, both authors reviewed the title and ab-
stract of the studies retrieved from the literature search for eligi-
bility. In the second phase, the full text of the articles which met the
inclusion criteria in phase one was skim-read to ensure consistency
with the eligibility criteria. The articles that met the inclusion cri-
teria were then reviewed in detail for data extraction.
Data extraction
M.U.K. extracted the data from the eligible studies. A proportion
of extracted data were then reviewed by P.A. for consistency. The
3
data were extracted using a piloted form (Tables 1 and 2). The form
extracted the following information: author(s) and publication year,
country, study design, study duration, population studied, number
of participants, adherence definition used, study measure, type of
medication, adherence phase, factors affecting medication adher-
ence, and summary critique. Any ambiguity during this process was
addressed through a discussion between the authors.
Quality assurance
This was a narrative review, which was conducted in a sys-
tematic manner to improve the methodological rigor. Therefore, the
reporting of this narrative review was guided by the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) guidelines, an approach commonly utilized in system-
atic reviews (Moher et al. 2009) (Supplementary Table S2). For the
quality assessment of the selected studies, we followed an alter-
native approach. The Centre for Reviews and Dissemination (CRD)
guideline suggests the use of a structured strategy to assess the
quality of articles for inclusion in systematic reviews (Centre for
Reviews and Dissemination 2010). However, it also acknowledges
the complexities surrounding the definition of quality. Scholars
suggest the inclusion of a critique of individual studies in the nar-
rative review to allow the readers to decide on the quality of the
studies (Dixon-Woods et al. 2005; Lakhanpaul et al. 2014). The
same approach has been used in this review.
Data synthesis
The studies that met the eligibility criteria varied considerably in
terms of their design and methods. For example, both quantitative
and/or qualitative methods were used to address study questions
using a range of study measures. Results were synthesized in the
form of a narrative report in view of the heterogeneity among
studies, as suggested elsewhere (Dixon-Woods et al. 2005; Popay
et al. 2006; Lakhanpaul et al. 2014).
Results
Study selection
A total of 1370 records were identified through database
searching (Fig. 1). After removing the duplicates, 424 articles were
screened against the selection criteria based on their titles and ab-
stracts. This resulted in the exclusion of 298 articles because of not
meeting the inclusion criteria. The full text of the remaining articles
(n = 126) was reviewed and assessed for eligibility, of which 81
articles were further excluded for not meeting the inclusion criteria,
resulting in the inclusion of 48 articles for qualitative synthesis.
Study characteristics
An overview of the study characteristics is presented in Table 1.
Most studies were conducted in the United States (n = 17) (Rieppi
et al. 2002; Monastra 2005; Faraone et al. 2007; Safren et al. 2007;
Barner et al. 2011; Hodgkins et al. 2011; Brinkman et al. 2012;
Coletti et al. 2012; Cormier 2012; Palli et al. 2012; Toomey et al.
2012; Fiks et al. 2013; O’Callaghan 2014; Bali et al. 2015; Li et al.
2017; Schaefer et al. 2017; Sleath et al. 2017) followed by Canada
(n = 5) (Thiruchelvam et al. 2001; Miller et al. 2004; Charach et al.
2006; Darredeau et al. 2007; Hebert et al. 2013), Taiwan (n = 4)
(Chen et al. 2011; Gau et al. 2006, 2008; Wang et al. 2016), Sweden
(n = 4) (Thorell and Dahlström 2009; Bejerot et al. 2010; Bahma-
nyar et al. 2013; Emilsson et al. 2017), Korea (n = 3) (Hong et al.
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Table 1. Study Characteristics

Number of
First author (Ref) Year Country Study design Study duration Participants participants

Ahmed et al. 2017 Australia Prospective (qualitative) 3 focus groups with a total Parents 16
duration of 3–4.5 hours
Atzori et al. 2009 Italy Prospective (quantitative 36 months Children adolescents 134
and qualitative)
Ayaz et al. 2014 Turkey Prospective (quantitative 12 months Children adolescents 877
and qualitative)
Bahmanyar et al. 2013 Sweden Retrospective (quantitative) 4 years Children adolescents 7931
Bali et al. 2015 United States Retrospective (quantitative) 2 years and 6 months Children adolescents 39,981
Barner et al. 2011 United States Retrospective (quantitative) 6 years and 6 months Children adolescents 62,789
Bejerot et al. 2010 Sweden Prospective (quantitative) 5 years and 8 months Adults 133
Bhang et al. 2017 Korea Retrospective (quantitative) 5 years Children adolescents 69,631
Bijlenga et al. 2017 The Netherlands Prospective (quantitative) 3 years Adults 233
Brinkman et al. 2012 United States Prospective (qualitative) 2 months Parents 122
Charach et al. 2006 Canada Prospective (qualitative) Not mentioned Parents 17
Chen et al. 2011 Taiwan Retrospective (quantitative) 5 years Children adolescents 10,153

4
Coletti et al. 2012 United States Prospective (qualitative) 3 months Parents 27
Cormier 2012 United States Prospective (qualitative) 10 months Parents 16
Darredeau et al. 2007 Canada Prospective (qualitative 12 months Adults 66
and quantitative)
Emilsson et al. 2017 Sweden Prospective (quantitative) 15 months Adolescents 101
Faraone et al. 2007 United States Prospective (quantitative) 12 months Children 407
Fiks et al. 2013 United States Prospective (quantitative) 6 months Parents 237
Gau et al. 2008 Taiwan Prospective (quantitative) 11 months Children adolescents 607
Gau et al. 2006 Taiwan Prospective (quantitative) Not mentioned Parents 307
Hebert et al. 2013 Canada Prospective (qualitative) 2 years Parents 33
Hodgkins et al. 2011 United States Retrospective 2 years and 9 months Children adolescents adults 23,860
(quantitative)
Hong et al. 2016 Korea Retrospective (quantitative) 3 years Children adolescents 15,133
Hong et al. 2014 Korea Retrospective (quantitative) 4 years Children adolescents 300
Hong et al. 2013 Central Europe and Prospective (quantitative) 1 year Children adolescents 1068
East Asia
Kooij et al. 2013 Europe Prospective (quantitative) 15 months Adults 276
Li et al. 2017 United States Retrospective (quantitative) 1 year Adults 3545
(continued)
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Table 1. (Continued)

Number of
First author (Ref) Year Country Study design Study duration Participants participants

Miller et al. 2004 Canada Retrospective (quantitative) 6 years Children adolescents 16,945
Monastra 2005 United States Prospective (quantitative) 2 years Parents 856
O’Callaghan 2014 United States Prospective (quantitative Not mentioned Adults 67
and qualitative)
Palli et al. 2012 United States Retrospective (quantitative) 3 years Children adolescents 46,135
Raman et al. 2015 United Kingdom Retrospective (quantitative) 15 years and 5 months Children adolescents 2878
Rieppi et al. 2002 United States Prospective (quantitative) 14 months Children 579
Safren et al. 2007 United States Prospective (quantitative) Not mentioned Adults 31
Schaefer et al. 2017 United States Prospective (qualitative) Not mentioned Adolescents 10
Semerci et al. 2016 Turkey Retrospective (quantitative) Not mentioned Adults 102
Sitholey et al. 2011 India Prospective (quantitative) Not mentioned Parents 24
Sleath et al. 2017 United States Prospective (quantitative) Not mentioned Adolescents 70

5
Sobanski et al. 2014 Germany Prospective (quantitative) 24 weeks Adults 241
Thiruchelvam et al. 2001 Canada Prospective (qualitative) 5 years Children 71
Parents
Thorell and Dahlström 2009 Sweden Prospective (quantitative) Not mentioned Children Parents 158 (79 children and one
parent of each child)
Toomey et al. 2012 United States Prospective (quantitative) 6 months Parents 127
Torgersen et al. 2012 Norway Retrospective (quantitative) 8 years Adults 117
Treuer et al. 2014 China, Egypt, Lebanon, Prospective (quantitative) 12 months Children adolescents 546
Russian Federation,
Taiwan, United Arab
Emirates
van den Ban et al. 2010 The Netherlands Retrospective (quantitative) 5 years Children adolescents 13,489
adults (<45)
Wang et al. 2016 Taiwan Retrospective (quantitative) Not mentioned Children adolescents 112,140
Wehmeier et al. 2015 Germany Prospective (quantitative) 12 months Children adolescents 504
Wong et al. 2009 United Kingdom Retrospective (quantitative) 8 years Adolescents 983
Prospective (qualitative) 120

Table 2. Studies Examining Factors Affecting Medication Adherence in Patients with Attention-Deficit/Hyperactivity Disorder
First author
(Ref) Adherence definition
Ahmed et al. Initiation: factors that led participants to
(2017) commence therapy
Continuation: factors that encouraged
parents to persist with the therapy
Cessation: factors that led to
discontinuation of therapy
Atzori et al. Medication adherence was defined as
(2009) medication intake of at least 80% with
no more than 4 months gap per year
Ayaz et al. Medication persistence was defined as a
(2014) continuity of medicine intake from
initiation throughout 12 months period
with a max gap of 3 months.
Bahmanyar et Adherence was defined as no purchase of
al. (2013) medicine during a period of six months
after medication initiation
Bali et al. Medication persistence was defined as a
(2015) time period from initiation to
6
discontinuation
Barner et al. Adherence was defined in terms of MPR:
(2011) proportion of days the medicines were
in possession of a patient
Persistence: number of days of continuous
therapy (allowable gap period of 30
days was specified) during the
postindex period
Bejerot et al. Not mentioned
(2010)
Bhang et al. Adherence was defined in terms of MPR:
(2017) the proportion of days that patients
were in possession of their prescribed
medication with the cutoff of 80%
persistence was defined as the number
of days of continuous therapy (without
a 30-day gap period) during the
postindex period
Bijlenga et al. Adherence (also termed compliance) is the
(2017) extent of conformity to the prescription
with respect to the timing, dosage, and
frequency
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Adherence Measure used to
phase examine factors Medication Factors affecting adherence Critique
Initiation Focus group discussions Methylphenidate, Child’s academic and social performance, advice of health Sample was relatively small and
Implementation Dexamphetamine care professionals (HCPs), and positive feedback from representative of a single metropolitan
Discontinuation Atomoxetine parents of other children encouraged initiation of area. Medication related factors such as
medication. medication type and effect of dosing
Improved symptoms and improved academic and social information were not examined.
performance predicted higher adherence
Side effects, addiction to or abuse of medication, impact of
medicine on growth, and social stigma predicted higher
rate of discontinuation
Implementation Data generated from IR–Methylphenidate Comorbidity, younger age, female gender, and family Method of adherence assessment was not
Discontinuation interview and Pill status (not living with both parents) predicted higher clear. Study was carried out in setting
count adherence where stimulant prescriptions were
Functional remission, lack of effectiveness, side effects, associated with higher restrictions. Sample
and old age increased discontinuation size was small. Homogenous population
limits the generalizability of findings.
Implementation Insurance claims SA MPH, LA MPH, Younger age, increased symptoms, addition of another Diagnosis of psychiatric comorbidity was
database, Telephonic Atomoxetine ADHD or psychiatric medicine, absence of side effects, not based on structured evaluations.
Interviews and lower CGI-I score (improvement in condition) were Factors like medication effectiveness and
associated with higher persistence side effects were not evaluated.
Implementation Medical record database Methylphenidate Older age and concomitant psychiatric disorder were at risk Data from the primary care clinics were not
Atomoxetine of poor adherence included where most of the consultations
Amphetamine take place
dexamphetamine
Implementation Medical and prescription Methylphenidate, Concomitant use of psychiatric medicines, children, Population was not randomized, which may
claims data Dexmethylphenidate, seasonal (winter) and geographic variations, and lead to selection bias. Only long-acting
Mixed amphetamine salts, presence of psychiatric comorbidity (depression, medications were examined.
Pemoline, anxiety, and OCD) were associated with longer Demographic information such as
Lisdexamfetamine persistence. income, education, and race.
dimesylate
Implementation Prescription claims data Immediate release stimulants, Medication type (nonstimulants), female gender, increase Some important variables such as frequency
Extended release in number of medication in general, and comorbid and severity of side effects, parent
stimulants, Prodrug medications predicted higher adherence education, and family history were not
stimulant, Nonstimulant examined in this study.
Implementation Self-reported Methylphenidate, Medication effectiveness predicted higher adherence Limited sample size may not represent the
Discontinuation questionnaire Dexamphetamine Anxiety/depression, lack of effectiveness, and side effects entire population. The study used tougher
predicted early discontinuation eligibility criteria that led to exclusion of
participants with alcohol abuse. Majority
of participants had higher education and
socioeconomic status.
Implementation Insurance claims IR- Methylphenidate Medication type (atomoxetine), older age (10–15), National health insurance data (from where
database ER- Methylphenidate prescription by specialist, and comorbid psychiatric participants were identified) may not
OROS- Methylphenidate condition were associated with higher adherence include patients with private insurance.
Atomoxetine Information was not clear regarding the
adjustment of confounding factors.
Implementation Questionnaire followed IR and ER methylphenidate, Higher educational level and the combined ADHD subtype Small sample size. Questionnaire was not
by telephonic IR and ER were related to nonadherence validated.
interview dextroamphetamine
(continued)
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Table 2. (Continued)

First author Adherence Measure used to

(Ref) Adherence definition phase examine factors Medication Factors affecting adherence Critique

Brinkman et al. Not mentioned Initiation Focus group discussion Stimulants Parents’ recognition of child functional problems, There was a considerable homogeneity
(2012) medication beliefs, medication effectiveness, side among participants. Parents who did not
effects, relationship with physician, family support, and participate in this study may have had
drug addiction affected initiation of medication some different views on treatment
initiation.
Charach et al. Adherence was measured by the question: Implementation Questionnaire Stimulants Physical side effects (heartburn, increased blood pressure, The study did not examine the effect of
(2006) Are you currently using stimulants to (quantitative) insomnia, and weight loss), psychological side effects some important factors on adherence
treat ADHD? Participants selected one Telephone interview (feeling anxious, irritable, and emotionally out of such as comorbidity and symptom
of three options: Yes, everyday; (qualitative) control) and lack of effectiveness, health insurance and/ severity. Sample size was limited.
Sometimes, when needed; No, not at or prescription coverage predicted lower adherence
all.
Chen et al. Not mentioned Initiation Focus group discussions Stimulants Medication safety, social influence, conflicting information, Small sample size and inclusion of
(2011) and negative media portrayal of medication use participants from a single medical center
prevented initiation may not represent the entire ADHD
population.
Coletti et al. Adherence was defined in terms of Initiation Health insurance Methylphenidate Lower socioeconomic status, older age, diagnosed during Limited numbers of factors were studied due
(2012) medication initiation after prescription Discontinuation database school days, receiving prescription from specialist, to lack of data. Data were obtained from
or discontinuation with a gap of 90 receiving diagnosis from district hospital/clinic were a single database, hence may not be
days. associated with earlier initiation generalizable to other insurance plans.
Prescription from hospital or clinics (compared to medical
center) predicted higher rate of discontinuation, while
change of treatment center reduced rate of
discontinuation by 58%.

7
Cormier (2012) Adherence was defined in terms of Initiation Focus group discussion Stimulants and nonstimulants Concerns about side effects and belief about medications Confounding factors such as access to
medication initiation after prescription affected medication initiation mental health services were not taken
into account, which may have affected
decision to initiate rather than the
reported factors.
Darredeau et Not provided Initiation Semistructured Stimulants and nonstimulants Negative beliefs, social stigma, and concerns about side Limited heterogeneity of the sample may not
al. (2007) Implementation interviews with effects delayed the initiation of medication represent the findings of the true
parents Medication effectiveness predicted higher adherence population.
Emilsson et al. Adherence was defined as number of days Implementation Structured face-to-face Methylphenidate Community support and absence of substance use predicted Conveniently selected sample may not be
(2017) medication taken in the same way as interviews and record higher adherence representative of true population. Self-
prescribed in the past 30 days of medication reported data may have resulted in
histories socially-desirable response.
Faraone et al. Adherence was defined as >92% of total Implementation Self-reported Methylphenidate Combination therapy of MPH and ATX predicts The relative homogeneity among
(2007) Medication Adherence Report Scale questionnaire Atomoxetine nonadherence than MPH alone. participants limits the generalizability of
score. (medication the findings. The questionnaire used had
adherence report limited reliability (lower internal
scale, MARS) consistency), and validity (only item
intercorrelations) was performed.
Fiks et al. Adherence was defined as the total Implementation Dosing record OROS MPH Older age, low starting dose, minority ethnic status Findings may not be similar in naturalistic
(2013) number of days medication was taken (African American, Hispanic, Asian), and fewer ADHD settings. No detail information is
divided by the total number of days on symptoms were associated with low adherence provided on how the data regarding
study with the cutoff rate of 75%. adherence were noted on the dosing
record.
Gau et al. Medication adherence was defined as Initiation Self-reported Methylphenidate, Medication acceptability (beliefs) and achievement of Limited use of covariates may have limited
(2008) initiation of medicines after a 6-month questionnaire amphetamine, atypical academic goals were associated with treatment initiation the findings related to factors leading to
follow-up period. antipsychotics medication initiation.
(continued)

First author
(Ref) Adherence definition
Gau et al. Poor adherence was defined as missing at
(2006) least 1 dose on a school day on at least
2 days a week for 4 weeks
Hebert et al. Poor adherence was defined as maternal
(2013) reports of a child missing more than 14
days of any dose of immediate-release
methylphenidate on a daily basis for
the past 1 month
Hodgkins et al. Adherence was defined as a continuous
(2011) percentage in terms of number of days
of medication per week/over 7 days per
week
Hong et al. Medication persistence was defined as the
(2016) number of days patient remained on
the drug initially prescribed
Adherence was defined in terms of MPR:
the ratio of the number of days of the
initial therapy supplied to the total
number of days persistent
Hong et al. Persistence was defined as the number of
8
(2014) days of continuous therapy without a
specified gap (15 days and 30 days)
period during the post-index period
Hong et al. Adherence was defined in terms of MPR:
(2013) Number of days of medication supplied
within the refill interval/number of
days in the refill interval
Kooij et al. Adherence was determined for the week
(2013) prior to follow-up based on the
information obtained through the
questionnaire by the physician
Li et al. (2017) Adherence was defined as the ratio of
capsules taken on a day to capsules
prescribed by the protocol Overall
adherence was taken as the average
adherence for 13 weeks. Patients were
defined as adherent if their overall
adherence was >95%.
Miller et al. Initiation was defined as having at least 1
(2004) pharmacy claim for ADHD
medications within the 6-month fixed
time window after the index date.
Monastra Persistence was defined as continuity of
(2005) therapy between first and last
prescription with a max gap of 4
months
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Table 2. (Continued)
Adherence Measure used to
phase examine factors Medication Factors affecting adherence Critique
Implementation Interviews and self- IR-methylphenidate Poor adherence was related to older age (continuous Objective assessment of adherence was done
Discontinuation reported questionnaire variable), family history, paternal education of college by an interviewer based on the
or higher, high frequency of MPH, and high dose of participants’ response. The possibility of
MPH interviewer-related bias may have
Treatment at national medical center, higher dose of MPH, affected the findings.
multidose administration, and more severe inattention
symptoms predicted higher rate of discontinuation
Implementation Self-reported IR- Methylphenidate Older age and increased frequency of medication predicted Possibility of recall bias exists in this study.
questionnaire poor adherence Limited factors were studied.
Confounding factors were not taken into
account.
Implementation Parents’ interviews slow-release Male gender and psychosocial benefits predicted higher Influence of gender on adherence in this
methylphenidate, adherence study could be debatable due to small
lisdexamfetamine number of females (n = 7) compared to
males (n = 26).
Implementation Medical and Pharmacy All stimulants and long- Medication type (LA medications) and younger age Data obtained from the claims form were
Discontinuation claims database acting nonstimulants predicted higher adherence limited in terms of economic and clinical
(only MPH) Psychiatric comorbidity, medication count, and female information. These factors may have
gender predicted early discontinuation demonstrated adherence to medication.
Discontinuation Health insurance IR- Methylphenidate Decreased ADHD-related hospital visit led to higher Demographic variables were not studied due
database ER- Methylphenidate discontinuation to availability issues.
OROS- Methylphenidate
Atomoxetine
Initiation Medical record database Methylphenidate Younger age, younger parents, high maternal education, Data retrieved from a single database may
and high patient IQ were likely to drop out before not account for other settings. Some
initiation important factors such as psychiatric
comorbidity were not considered.
Implementation Questionnaire All stimulants and Geographic variation (East Asia), family history, parental Those participants who were willing to
nonstimulants emotional problems, and no other children at home participate in long-term follow-up study
predicted lower adherence were included. Findings may not be
representative of true clinical sample.
Implementation MPR OROS MPH Male gender, increased time since diagnosis, and high This was a randomized control trial; hence,
school education were associated with higher adherence. the findings may not represent the real
Psychiatric problems led to lower adherence world settings. Several key factors such
as psychiatric comorbidity and number of
doses were not evaluated.
Initiation Medical record database Methylphenidate, Male, racial and ethnic minorities, younger age groups, Study participants were those enrolled in
Dexmethylphenidate, severe mental comorbidities and, concordantly, use of Medicaid program; hence, results are
Mixed amphetamine salts, antipsychotics or mood stabilizers had a decreased mainly valid to low-income population.
Dextroamphetamine, propensity for treatment initiation
Methamphetamine,
Pemoline, Atomoxetine
Implementation Medical record database Methylphenidate Younger age, male gender, and prescription from Patients taking ADHD medication other
psychiatrist predicted higher adherence than MPH were not included. This may
affect the external validity of the
findings.
(continued)
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Table 2. (Continued)

First author Adherence Measure used to

(Ref) Adherence definition phase examine factors Medication Factors affecting adherence Critique

O’Callaghan Not defined Implementation Parents’ questionnaire Methylphenidate Side effects and lack of confidence in assessment process Reliability and validity of the survey were
(2014) Discontinuation Amphetamine predicted lower adherence not mentioned.
Side effects and persistence of symptoms promoted
discontinuation
Palli et al. Persistence was defined as the consecutive Implementation Claims database Stimulants Ethnicity (African, Hispanic), age (6–12), year of entry into Limited number of factors was studied.
(2012) refill history during a treatment period Nonstimulants cohort, foster care, starting the index medication during Adherence was based on the assumption
with a gap of 30 days between refills. autumn or winter, diagnosis of bipolar disorder or that the medication has been taken as
psychosis, and concurrent psychotropic medication prescribed if it has been dispensed to the
predict persistence patient.
Raman et al. Medication persistence was defined as Implementation Electronic patient record IR methylphenidate, LA Medication type (LA MPH) predicted higher adherence Diagnostic criteria to define ADHD were
(2015) continuous treatment for 6 months after data methylphenidate, unknown. The stringent eligibility
initiation atomoxetine, criteria may have resulted in exclusion
dexamphetamine of ADHD patients and the loss of some
critical information about factors
affecting adherence.
Rieppi et al. Adherence was defined as acceptance of Implementation Parents self-reported Stimulants None identified Only the socioeconomic status was studied.
(2002) assigned treatment and attendance at questionnaire Nonstimulants
‡80% of appointments (not specified)
Safren et al. Medication adherence was defined as a Implementation Self-reported All stimulants and Severity of ADHD symptoms was associated with lower Confounding factors were not controlled.
(2007) total number of dosage units ingested questionnaire nonstimulants adherence Sample size was relatively small.
compared to the total number of
dosage units prescribed in a given time
period with the cutoff rate of 80%.
Schaefer et al. No definition was provided Implementation Individual Interviews, Not mentioned Side effects and false beliefs about ADHD medications Provision of social desirability responses,
(2017) self-reported predicted lower adherence convenience sampling method, and
questionnaire limited sample size may affect the

9
generalizability.
Semerci et al. Adherence was defined as the extent to Implementation Medical record database LA- Methylphenidate University education and family history predicted higher Participants were highly educated and were
(2016) which patients take medication as Atomoxetine adherence mostly males. Use of patients’ report
prescribed by their health care provider enhances the possibility of recall bias.
Sitholey et al. Nonadherence was defined as taking less Implementation Parents’ self-reported IR- Methylphenidate Side effects, fear of addiction, medication access, perceived Sample size was relatively small. No
(2011) than 80% of prescribed medication questionnaire Clonidine medication ineffectiveness, medication cost, social information was provided about the
and/or not visiting clinic within 2 influence, medication frequency, and duration of reliability and validity of the
weeks of the scheduled appointment. therapy were associated with poor adherence questionnaire. Procedure to assess
adherence was not clear.
Sleath et al. Not provided Implementation Visual analog scale Not specified Nonwhite and older youth were less likely to be adherent Some potential factors such as concomitant
(2017) psychiatric diseases were not considered
in this study.
Sobanski et al. Adherence was defined as >80% intake of Implementation Pill count and other MPH-ER Patient’s education (lower than secondary school), no Since the patients were randomized, it is
(2014) the dispensed medication according to Discontinuation patient-related, family history, mild-to-moderate symptoms, and difficult to translate these results into
pill count, during the study period. treatment-related, and decreased medication effectiveness were associated routine clinical settings.
disorder-related with nonadherence.
information obtained Male gender, low MPH dose, and lower education
through a predicted higher discontinuation rate.
questionnaire
Thiruchelvam Adherence was defined as the child taking Implementation Semistructured interview Methylphenidate Younger age (range was not mentioned), increased number Decreased follow-up in later phases of study
et al. (2001) the studied drugs for at least 5 days a Dextroamphetamine of ADHD symptoms, and absence of ODD were resulted in fewer observation regarding
week throughout the follow-up period Pemoline associated with higher adherence. medication adherence.
(max gap of 14 weeks was allowed per
year)
Thorell and Not mentioned Implementation Children self-reported Methylphenidate Academic and social performance and negative parental Information about reliability and validity
Dahlström questionnaire and Amphetamine views on medications were associated with poor of the questionnaire was clear.
(2009) parents’ self-reported adherence
questionnaire
(continued)
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Table 2. (Continued)

First author Adherence Measure used to

(Ref) Adherence definition phase examine factors Medication Factors affecting adherence Critique

Toomey et al. Medication discontinuation was defined as Discontinuation Telephone survey Stimulants (specific Medication side effects, medication effectiveness, and Information regarding the validity and
(2012) children not taking ADHD medicines medications not mental health comorbidity predicted higher rate of reliability of the survey was not
at the time of survey as reported by mentioned) discontinuation provided.
parents
Torgersen et al. Medication adherence was defined as the Implementation Medical record database MPH-IR, MPH-ER, OROS Medication type (extended release), use of second Data were only collected by a single author.
(2012) use of drug for 36 months with a gap of MPH, dexamphetamine stimulant, higher dose, and less side effects were linked The chances of observer bias could not
no more than 3 months. IR to higher adherence be ignored.
Treuer et al. Medication persistence: length of time Discontinuation Self-reported Methylphenidate, Low initial dose predicted higher rate of discontinuation Dose of atomoxetine was missing for several
(2014) from initiation to discontinuation questionnaire atomoxetine patients. Findings may not be
generalizable to the entire population.
van den Ban et Nonadherence was defined as not having Discontinuation Prescription record IR- Methylphenidate Females and older age (>18) were more likely to Study did not ensure if the data are of
al. (2010) refilled a new prescription for any review ER- Methylphenidate discontinue ADHD patients rather depended on
ADHD drug within 3 months after the Atomoxetine ADHD medication to assume patient
theoretical end date of the previous would have ADHD. Treatment-related
prescription factors were not studied.

10
Wang et al. Initiation: Initiation of medication after Initiation Insurance claims data Immediate release (IR) Male gender and psychiatric comorbidity predicted higher Participants were not screened through the
(2016) first prescription Discontinuation methylphenidate, Osmotic possibility of initiation diagnostic procedure.
Discontinuation: Cessation of medication controlled-release oral Female gender, older age, and psychiatric comorbidity Several sociodemographic and clinical
for 180 days or longer delivery system (OROS) predicted early discontinuation factors were included because of
methylphenidate, nonavailability of data.
Atomoxetine (ATX)
Wehmeier et Medication adherence was defined as the Implementation PCSR questionnaire Stimulants None identified significant No information was provided about the
al. (2015) presence of a Pediatric Compliance Atomoxetine survey used in this study.
Self-Rating instrument (PCSR) score
‡5 at all visits documented.
Wong et al. Medication cessation was defined as a Discontinuation Medical record database IR methylphenidate, LA Gender (female) and year of study entry (patients aged 15 Retrospective analysis failed to collect data
(2009) minimum gap of 6 months between Individual Interviews methylphenidate, between 1999 and 2003 were more likely to discontinue about some essential factors (severity of
prescriptions. atomoxetine, than the patients of the same age between 2004 and symptoms and socioeconomic status),
dexamphetamine 2006) predicted higher adherence which may have predicted adherence.

Adherence definition was taken from the studies, while adherence phase was based on authors’ interpretation.
ADHD, attention-deficit/hyperactivity disorder; MPR, medication possession ratio; ODD, oppositional defiant disorder.
 FACTORS INFLUENCING ADHERENCE TO ADHD MEDICATION
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FIG. 1. PRISMA flow diagram.
2014, 2016; Bhang et al. 2017), United Kingdom (n = 2) (Wong
et al. 2009; Raman et al. 2015), Turkey (n = 2) (Ayaz et al. 2014;
Semerci et al. 2016), Germany (n = 2) (Sobanski et al. 2014;
Wehmeier et al. 2015), the Netherlands (n = 2) (van den Ban et al.
2010; Bijlenga et al. 2017), Italy (n = 1) (Atzori et al. 2009), India
(Sitholey et al. 2011), Australia (n = 1) (Ahmed et al. 2017), and
Norway (n = 1) (Torgersen et al. 2012). The three remaining studies
were multicenter studies conducted in different parts of nonwestern
countries (Treuer et al. 2014), Central Europe and East Asia (Hong
et al. 2013), and Europe (Kooij et al. 2013). All studies were
published between 2001 and 2017. Most studies collected data
prospectively (n = 31) (Thiruchelvam et al. 2001; Rieppi et al.
2002; Monastra 2005; Charach et al. 2006; Gau et al. 2006, 2008;
Darredeau et al. 2007; Faraone et al. 2007; Safren et al. 2007;
Atzori et al. 2009; Thorell and Dahlström 2009; Bejerot et al. 2010;
Sitholey et al. 2011; Brinkman et al. 2012; Coletti et al. 2012;
Cormier 2012; Toomey et al. 2012; Fiks et al. 2013; Hebert et al.
2013; Hong et al. 2013; Kooij et al. 2013; Ayaz et al. 2014;
O’Callaghan 2014; Sobanski et al. 2014; Treuer et al. 2014;
Wehmeier et al. 2015; Ahmed et al. 2017; Bijlenga et al. 2017;
Emilsson et al. 2017; Schaefer et al. 2017; Sleath et al. 2017)
compared to retrospective studies (n = 16) (Miller et al. 2004; van
den Ban et al. 2010; Barner et al. 2011; Chen et al. 2011; Hodgkins
et al. 2011; Palli et al. 2012; Torgersen et al. 2012; Bahmanyar et al.
2013; Hong et al. 2014, 2016; Bali et al. 2015; Raman et al. 2015;
11
Semerci et al. 2016; Wang et al. 2016; Bhang et al. 2017; Li et al.
2017), while 1 study used both approaches (Wong et al. 2009). The
majority of studies included both children and adolescents as study
participants (n = 17) (Miller et al. 2004; Gau et al. 2008; Atzori
et al. 2009; Barner et al. 2011; Chen et al. 2011; Palli et al. 2012;
Bahmanyar et al. 2013; Hong et al. 2013; Ayaz et al. 2014; Hong
et al. 2014; Treuer et al. 2014; Bali et al. 2015; Raman et al. 2015;
Wehmeier et al. 2015; Hong et al. 2016 Wang et al. 2016; Bhang
et al. 2017) followed by parents (n = 11) (Monastra 2005; Charach
et al. 2006; Gau et al. 2006; Sitholey et al. 2011; Brinkman et al.
2012; Coletti et al. 2012; Cormier 2012; Toomey et al. 2012; Fiks
et al. 2013; Hebert et al. 2013; Ahmed et al. 2017), adults (n = 10)
(Darredeau et al. 2007; Safren et al. 2007; Bejerot et al. 2010;
Torgersen et al. 2012; Kooij et al. 2013; O’Callaghan 2014; So-
banski et al. 2014; Semerci et al. 2016; Bijlenga et al. 2017; Li et al.
2017), adolescents (n = 4) (Wong et al. 2009; Emilsson et al. 2017;
Schaefer et al. 2017; Sleath et al. 2017), children (n = 2) (Rieppi
et al. 2002; Faraone et al. 2007), children and parents (n = 2)
(Thiruchelvam et al. 2001; Thorell and Dahlström 2009), and
children, adolescents, and adults (n = 2) (van den Ban et al. 2010;
Hodgkins et al. 2011). The study duration varied from 2 months to 4
years in prospective studies and 2.5 years to 15.6 years in retro-
spective studies. The number of participants varied from 102 to
112,140 in retrospective studies and 10 to 1068 in prospective
studies.
 12
Results of individual studies
Table 2 summarizes the results of individual studies with regards
to the definition of adherence, use of adherence measures, adher-
ence phase, and factors affecting medication adherence.
Adherence definition
A considerable variation was observed regarding the criteria
used to define adherence. Some studies (Barner et al. 2011;
Hodgkins et al. 2011; Hong et al. 2014; Bhang et al. 2017) defined
adherence in terms of medication possession ratio by determining
the proportion of days patients were in possession of their medi-
cines. Some studies defined adherence based on gaps in therapy
(Thiruchelvam et al. 2001; Gau et al. 2006, 2008; van den Ban et al.
2010; Chen et al. 2011; Torgersen et al. 2012). Some defined gaps
as no more than 3 months (Thiruchelvam et al. 2001; van den Ban
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et al. 2010; Chen et al. 2011; Torgersen et al. 2012), while others
took it as missing at least 1 dose on a school day for at least 2 days
per week for 4 weeks (Gau et al. 2008) or missing 14 days of
medication in a month (Gau et al. 2006). A few studies used a cutoff
score achieved by patients after using medication adherence in-
struments to evaluate and define adherence (O’Callaghan 2014;
Hong et al. 2013; Wehmeier et al. 2015; Emilsson et al. 2017). For
example, medication adherence was defined as the presence of a
Pediatric Compliance Self-Rating score of ‡5 on a scale of 1–7
(Wehmeier et al. 2015).
Persistence definition
Persistence was generally defined as continuity of therapy from
initiation (Miller et al. 2004; Barner et al. 2011; Hodgkins et al.
2011; Palli et al. 2012; Ayaz et al. 2014; Treuer et al. 2014; Bali
et al. 2015; Raman et al. 2015; Hong et al. 2016). However, the
length of continuity varied among studies along with the allowed
gap (no medication taking) period. It was observed that a gap of
1 month was allowed if persistence was measured over 6 months.
A maximum gap of 3 months was allowed if the persistence was
measured over a period of 12 months except for one study in which
a gap of 4 months was allowed (Miller et al. 2004). One study
defined persistence as taking more than 80% of prescribed medi-
cation according to the pill count method (Sobanski et al. 2014).
Definitions used for different phases of adherence
A limited number of studies (n = 6) defined the three phases of
adherence; initiation, implementation, and discontinuation (Wong
et al. 2009; Chen et al. 2011; Coletti et al. 2012; Fiks et al. 2013;
Wang et al. 2016; Ahmed et al. 2017). Initiation was defined as
commencement of therapy (Wang et al. 2016; Ahmed et al. 2017).
Implementation was defined in terms of continuation and persis-
tence with therapy (Ahmed et al. 2017). A couple of studies defined
discontinuation as the cessation of therapy for at least 6 months
(Wong et al. 2009; Wang et al. 2016). In contrast, a study assumed
discontinuation if the patient was not taking therapy at the time of
the survey (Toomey et al. 2012). Another study defined discon-
tinuation as the cessation of therapy without specifying the time
limit (Ahmed et al. 2017).
Use of measures to examine factors
affecting adherence
More than one-third of the studies utilized secondary databases
such as hospital prescription records or insurance databases to
KHAN AND ASLANI
identify factors affecting medication adherence (n = 18) (Miller
et al. 2004; Faraone et al. 2007; van den Ban et al. 2010; Barner
et al. 2011; Chen et al. 2011; Hodgkins et al. 2011; Palli et al. 2012;
Torgersen et al. 2012; Bahmanyar et al. 2013; Hong et al. 2013,
2014, 2016; Bali et al. 2015; Raman et al. 2015; Semerci et al. 2016;
Wang et al. 2016; Bhang et al. 2017; Li et al. 2017) followed by
questionnaire (n = 12) (Rieppi et al. 2002; Monastra 2005; Gau
et al. 2006; Safren et al. 2007; Thorell and Dahlström 2009; Bejerot
et al. 2010; Sitholey et al. 2011; Fiks et al. 2013; Hong et al. 2013;
Treuer et al. 2014; Wehmeier et al. 2015; Emilsson et al. 2017),
interviews (n = 3) (Thiruchelvam et al. 2001; Cormier 2012; Hebert
et al. 2013), and focus group discussions (n = 4) (Charach et al.
2006; Brinkman et al. 2012; Coletti et al. 2012; Ahmed et al. 2017).
A few studies (n = 4) used multiple measures (questionnaires and
interviews) to examine factors affecting adherence (Gau et al.
2008; O’Callaghan 2014; Bijlenga et al. 2017; Schaefer et al.
2017), while a couple of studies used a combination of prescription
records and interviews to collect data (Wong et al. 2009; Ayaz et al.
2014). The detailed description is presented in Table 2.
Studies examining factors affecting different phases
of adherence
When the studies were screened against the ABC taxonomy, it
was found that more than half of the studies (n = 27) examined the
factors affecting implementation of medication taking (Thir-
uchelvam et al. 2001; Rieppi et al. 2002; Miller et al. 2004; Gau
et al. 2006; Darredeau et al. 2007; Faraone et al. 2007; Safren et al.
2007; Thorell and Dahlström 2009; Barner et al. 2011; Sitholey
et al. 2011; Kooij et al. 2013; Palli et al. 2012; Torgersen et al. 2012;
Bahmanyar et al. 2013; Hebert et al. 2013; Hong et al. 2013; Ayaz
et al. 2014; O’Callaghan 2014; Bali et al. 2015; Raman et al. 2015;
Wehmeier et al. 2015; Semerci et al. 2016; Bhang et al. 2017;
Bijlenga et al. 2017; Emilsson et al. 2017; Schaefer et al. 2017;
Sleath et al. 2017). Only a handful of studies identified the factors
affecting initiation (n = 6) (Charach et al. 2006; Brinkman et al.
2012; Coletti et al. 2012; Fiks et al. 2013; Hong et al. 2014; Li et al.
2017) and discontinuation (n = 5) (Wong et al. 2009; van den Ban
et al. 2010; Toomey et al. 2012; Treuer et al. 2014; Hong et al.
2016) of ADHD medications. A few studies examined multiple
phases of adherence such as initiation and implementation (n = 1)
(Cormier 2012), initiation and discontinuation (n = 2) (Chen et al.
2011; Wang et al. 2016), and implementation and discontinuation
(n = 6) (Monastra 2005; Gau et al. 2008; Atzori et al. 2009; Bejerot
et al. 2010; Hodgkins et al. 2011; Sobanski et al. 2014). Only one
study evaluated the factors affecting all three phases of adherence
(n = 1) (Ahmed et al. 2017).
Factors affecting medication adherence in people
with ADHD
This review found that multiple factors affect medication ad-
herence in people with ADHD. A distinction has been made to
differentiate the factors based on the phase of adherence (initiation,
implementation, or discontinuation) defined by the ABC taxonomy
(Fig. 2). This review also differentiated the factors affecting med-
ication adherence in children, adolescents, and adults at each of the
three phases (Table 3).
Factors affecting the initiation phase of adherence
Medication beliefs and fear of side effects were the prominent
parent-related factors reported by most studies. Negative beliefs
 FACTORS INFLUENCING ADHERENCE TO ADHD MEDICATION
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FIG. 2. Factors influencing the three phases of medication adherence in patients with ADHD. ADHD, attention-deficit/hyperactivity
disorder.
were associated with lower rates of medication initiation (Brink-
man et al. 2012; Coletti et al. 2012; Fiks et al. 2013). Similarly, fear
of side effects negatively affected parents’ decision to initiate
medication (Charach et al. 2006; Brinkman et al. 2012; Coletti et al.
2012; Cormier 2012).
Three studies (Atzori et al. 2009; Chen et al. 2011; Wang et al.
2016) examined the factors affecting treatment initiation in children
and adolescents with ADHD. Age, gender, and psychiatric co-
morbidity were the frequently reported factors that affected medi-
cation initiation. Two studies linked the presence of psychiatric
comorbidity with a higher rate of medication initiation (Atzori et al.
2009; Wang et al. 2016). Older adolescents were more likely to
initiate their medication than younger ones (Chen et al. 2011). One
study [58] found that males were more likely to initiate medication,
while another study (Atzori et al. 2009) predicted higher initiation
rates among females. No study examined the factors associated with
the initiation of medication in adults with ADHD.
Factors affecting the implementation phase
of adherence
Medication effectiveness, side effects, and frequency of medi-
cation use were the frequently parent-related reported factors. Lack
of medication effectiveness in terms of academic and social per-
formance was associated with poor medication adherence (Thorell
and Dahlström 2009; Sitholey et al. 2011; Hebert et al. 2013;
Ahmed et al. 2017). Presence of side effects was also negatively
associated with medication adherence (Monastra 2005; Sitholey
et al. 2011; Cormier 2012). It was noted that the increased dosing
frequency of medications resulted in poor medication adherence
(Gau et al. 2006; Sitholey et al. 2011).
A total of 25 factors were identified among children. Age, psy-
chiatric comorbidity, concomitant use of psychiatric medications,
and medication type were the common factors identified in the
studies. Younger age was associated with higher rates of adherence
(Thiruchelvam et al. 2001; Miller et al. 2004; Faraone et al. 2007;
Gau et al. 2008; Atzori et al. 2009; Hodgkins et al. 2011; Bahmanyar
13
et al. 2013; Bhang et al. 2017). Two studies (Barner et al. 2011;
Bhang et al. 2017) reported that nonstimulants were associated with
higher adherence than stimulants, while other studies (Hodgkins
et al. 2011; Raman et al. 2015) reported that the use of long-acting
medications predicted higher adherence rates. Concomitant use of
psychiatric medications also predicted higher adherence (Barner
et al. 2011; Ayaz et al. 2014; Bali et al. 2015). Variation in findings
was observed regarding the presence of psychiatric comorbidity and
adherence. Four studies (Atzori et al. 2009; Palli et al. 2012; Bali
et al. 2015; Bhang et al. 2017) predicted higher adherence in patients
with psychiatric comorbidity, while two studies (Thiruchelvam et al.
2001; Bahmanyar et al. 2013) reported that the presence of co-
morbidity was associated with lower adherence.
A total of 23 factors were identified among adolescents. Age and
psychiatric comorbidity were the most frequently identified factors.
All but one study (Bhang et al. 2017) reported younger age to be
highly associated with medication adherence (Miller et al. 2004;
Gau et al. 2008; Atzori et al. 2009; Hodgkins et al. 2011; Bahma-
nyar et al. 2013; Ayaz et al. 2014). Similarly, except for one study
(Bahmanyar et al. 2013), most studies reported the presence of
psychiatric comorbidity to be associated with higher medication
adherence during implementation phase (Atzori et al. 2009; Barner
et al. 2011; Palli et al. 2012; Bahmanyar et al. 2013; Bali et al. 2015;
Bhang et al. 2017).
Patient education and medication effectiveness were the com-
mon factors affecting adherence to medication in adult patients.
Some studies demonstrated an association between medication
effectiveness and higher adherence (Darredeau et al. 2007; Fiks
et al. 2013), while other studies linked higher education with higher
medication adherence in adult patients (Kooij et al. 2013; Semerci
et al. 2016; Bijlenga et al. 2017).
Factors affecting the discontinuation phase
of adherence
Medication discontinuation was associated with medication ef-
fectiveness and side effects among parents. Lack of effectiveness
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Table 3. Factors Affecting Different Phases of Adherence in Patients with Attention-Deficit/Hyperactivity Disorder

No. of No. of
Adherence phase Participants Factors affecting adherence studiesa participants

Initiation Children & Gender, psychiatric comorbidity, socioeconomic status, age, diagnosis during school days, number of doctoral visit, parental 3 122,593
adolescents1 age, maternal education, IQ level
Adults None 0 0
Parents/carers2 Medication beliefs, achievement of academic goals, recognition of child functional problems, medication effectiveness, fear of 6 435
side effects, relationship with physician, family support, fear of drug addiction, advice of health care professionals (HCPs),
positive feedback from parents of other children, child’s social isolation, social stigma, conflicting information about
medication, and negative media portrayal of medication use
Implementation Children3 Medication type, gender, number of prescribed medication, age, family history, paternal education, high dose, increased 17 274,555
medication frequency, time since diagnosis, geographic variation, seasonal variation, psychiatric comorbidity, parental
emotional problem, number of children at home, starting dose, number of ADHD symptoms, ethnicity, side effects,
medication effectiveness, lower CGI score, number of coprescribed psychiatric medicine, family status (living with single
or both parents), academic and social performance, parental views on medications, and prescription from psychiatrist
Adolescents4 Medication type, gender, number of coprescribed medication, age, family history, paternal education, dose and frequency 16 273,451
of prescribed medications, side effects, medication beliefs, time since diagnosis, geographic variation, psychiatric
comorbidity, parental emotions, number of children at home, symptomatic response of medication, family status, ethnicity,
foster care, and prescription from psychiatrist
Adults5 Medication type, age, side effects, medication effectiveness, health insurance/prescription coverage, gender, time since 11 24,961
diagnosis, patient education, psychiatric comorbidity, dose, concomitant medication, severity of symptoms, family history,
community support, and presence of substance use disorder

14
Parents/carers6 Child’s age, number of symptoms, psychiatric comorbidity, medication effectiveness, child’s academic and social 8 1481
performance, gender, psychosocial benefits, negative parental views on medications, medication frequency, side effects,
lack of confidence in assessment process, fear of addiction, medication cost, social influence, and duration of therapy
Discontinuation Children7 Gender, age, psychiatric comorbidity, dose, medication count, place of treatment (hospital/GP), severity of symptoms, 8 176,062
multidose administration, functional remission, side effects, medication effectiveness, number of hospital visit
Adolescents8 Gender, psychiatric comorbidity, age, dose, medication count, multidose administration, severity of symptoms, medical 8 167,012
facility where medication was prescribed, functional remission, lack of effectiveness, side effects, number of hospital visit
Adults9 Psychiatric comorbidity, medication count, gender, dose, education, medication effectiveness, side effects, age 4 37,723
Parents/carers10 Side effects, medication effectiveness, psychiatric comorbidity, addiction or abuse, impact of medicine on growth, social 3 999
stigma
a
Total number of studies are more than 45 as one study has included more than one group of population.
1
Chen et al. 2011; Hong et al. 2014; Wang et al. 2016.
2
Charach et al. 2006; Brinkman et al. 2012; Cormier 2012; Coletti et al. 2012; Fiks et al. 2013; Ahmed et al. 2017.
3
Thiruchelvam et al. 2001; Rieppi et al. 2002; Miller et al. 2004; Faraone et al. 2007; Gau et al. 2008; Atzori et al. 2009; Thorell and Dahlström 2009; Barner et al. 2011; Hodgkins et al. 2011; Palli et al. 2012;
Bahmanyar et al. 2013; Hong et al. 2013; Ayaz et al. 2014; Bali et al. 2015; Raman et al. 2015; Wehmeier et al. 2015; Bhang et al. 2017.
4
Miller et al. 2004; Gau et al. 2008; Atzori et al. 2009; Barner et al. 2011; Hodgkins et al. 2011; Palli et al. 2012; Bahmanyar et al. 2013; Hong et al. 2013; Ayaz et al. 2014; Bali et al. 2015; Wehmeier et al. 2015; Bhang et al.
2017; Emilsson et al. 2017; Schaefer et al. 2017; Sleath et al. 2017; Raman et al. 2018.
5
Darredeau et al. 2007; Safren et al. 2007; Bejerot et al. 2010; Hodgkins et al. 2011; Torgersen et al. 2012; Kooij et al. 2013; O’Callaghan et al. 2014; Sobanski et al. 2014; Semerci et al. 2016; Bijlenga et al. 2017; Li
et al. 2017.
6
Thiruchelvam et al. 2001; Monastra 2005; Gau et al. 2006; Thorell and Dahlström 2009; Sitholey et al. 2011; Cormier 2012; Hebert et al. 2013; Ahmed et al. 2017.
7
Gau et al. 2008; Atzori et al. 2009; van den Ban et al. 2010; Hodgkins et al. 2011; Chen et al. 2011; Treuer et al. 2014; Hong et al. 2016; Wang et al. 2016.
8
Wang et al. 2016; Treuer et al. 2014; Hodgkins et al. 2011; Gau et al. 2008; Wong et al. 2009; Atzori et al. 2009; van den Ban et al. 2010; Hong et al. 2016.
9
Hodgkins et al. 2011; Sobanski et al. 2014; Bejerot et al. 2010; van den Ban et al. 2010.
10
Toomey et al. 2012; Monastra 2005; Ahmed et al. 2017.
 FACTORS INFLUENCING ADHERENCE TO ADHD MEDICATION
was associated with higher discontinuation rates (Monastra 2005;
Toomey et al. 2012), while the presence of side effects also resulted
in early medication discontinuation (Toomey et al. 2012; Ahmed
et al. 2017).
Eight studies examined the factors affecting discontinuation
among children with ADHD (Gau et al. 2008; Atzori et al. 2009;
van den Ban et al. 2010; Chen et al. 2011; Hodgkins et al. 2011;
Treuer et al. 2014; Hong et al. 2016; Wang et al. 2016). A total of 10
unique factors were identified. Psychiatric comorbidity and gender
were found to be the most common factors identified in the studies.
Female patients were more likely to discontinue their medication
(van den Ban et al. 2010; Hodgkins et al. 2011; Wang et al. 2016).
Patients with psychiatric comorbidity were also associated with
early medication discontinuation (Hodgkins et al. 2011; Wang et al.
2016). Similar factors influenced medication adherence among
adolescents and adults; however, the effect of these factors varied
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between studies. For example, females were more likely to dis-
continue their medication than males in adolescent and adult pa-
tients (Wong et al. 2009; Hodgkins et al. 2011; Wang et al. 2016) in
contrast to another study (Fiks et al. 2013) in which males were
more likely to discontinue medication than their female counter-
parts. Presence of psychiatric comorbidity was also associated with
early discontinuation of medication among adolescents and adult
patients (Bejerot et al. 2010; Hodgkins et al. 2011; Wang et al.
2016).
Discussion
Prior attempts have been made to review the factors affecting
medication adherence in people with ADHD (Gajria et al. 2014;
Treuer et al. 2016), but no efforts were made to identify the factors
affecting the three phases of adherence. This review has summa-
rized as much as possible the available literature and identified the
factors affecting adherence at its three phases. This differentiation
is essential to better understand the phenomenon of medication-
taking behavior and to devise tailored interventions to improve
medication adherence in people with ADHD.
This review observed a large variation in the criteria used to
define adherence in the selected studies. The findings indicated that
most studies focused on examining the factors affecting the im-
plementation phase of adherence, while only a handful of studies
focused on the initiation and discontinuation phase of adherence.
Some unique factors were identified that affected the specific
phases of adherence, while patient’s age, gender, fear of addiction,
medication effectiveness, parent’s education, number of hospital
visits, psychiatric comorbidity, and medication side effects influ-
enced all three phases of adherence. This review also identified that
factors affecting one phase of adherence differed with regards to
different groups; that is, parents/carers, children, adolescents, and
adults. Medication beliefs and fear of side effects were the main
parental factors that affected the initiation of medication. In con-
trast, age, gender, and psychiatric comorbidity were frequently
reported as the predictors of medication initiation among children
and adolescents. For the implementation phase, factors such as
medication effectiveness and side effects were related to parents,
age and psychiatric comorbidity were associated with children and
adolescents, while patient education and medication effectiveness
were related to adults. Medication effectiveness and fear of side
effects among parents mainly led to discontinuation of medication.
Although gender was the common factor among children, adoles-
cents, and adults that affected discontinuation, its effect on adher-
ence varied between studies.
15
Definition of medication adherence and its phases
Included studies appeared to have used different definitions of
the three phases of adherence. For example, Wang et al. (2016) and
Ahmed et al. (2017) defined initiation as the commencement of
therapy; however, Wang et al. (2016) considered commencement
as the first prescription of ADHD medication, while Ahmed et al.
(2017) considered commencement as the administration of medi-
cation. Different conceptual approaches were used to define im-
plementation. Variations in the definition of implementation were
not only evident between studies that used different conceptual
approaches but also between studies that used the same conceptual
approach. For example, when adherence during the implementation
phase was defined as conformity to prescription with respect to
dosage, one study (Gau et al. 2006) defined nonadherence as
missing at least 1 dose on a school day on at least 2 days a week for
4 weeks, while another study (Hebert et al. 2013) defined non-
adherence as missing more than 14 days of any dose on a daily basis
for the past 1 month. Similarly, when implementation was defined
as continuity of medication, some studies defined implementation
as continuation of medication for 12 months (Monastra 2005; At-
zori et al. 2009; Ayaz et al. 2014), while other studies defined
implementation as continuation at 6 months (Raman et al. 2015)
and 36 months (Torgersen et al. 2012). It is important to note that
amongst studies that used 12 months as a cutoff period, some
studies allowed a gap of 4 months (permissible time off medication)
(Monastra 2005; Atzori et al. 2009), while another study allowed a
gap of 3 months (Ayaz et al. 2014). Similarly, most studies (Wong
et al. 2009; Toomey et al. 2012; Wang et al. 2016; Ahmed et al.
2017) defined discontinuation as the cessation of therapy; however,
Wong et al. (2009) and Wang et al. (2016) considered cessation as
not taking medication for at least 6 months, while Toomey et al.
(2012) and Ahmed et al. (2017) did not use any cutoff period to
define discontinuation.
Considerable variability was also observed among studies with
regards to the definition of medication adherence, a finding con-
sistent with the literature on adherence in other disease states
(Hearnshaw and Lindenmeyer 2006; Banek et al. 2014). The lack of
consensus on a definition of adherence in different disease states
indicates that it is a universal issue amongst adherence research
(Vermeire et al. 2001; Gebbia et al. 2012; Verbrugghe et al. 2013).
Lack of consistency and uniformity in the use of operational defi-
nitions of medication adherence has hampered health outcome re-
search in the past (Cramer et al. 2008). A considerable number of
studies have examined the factors affecting the medication-taking
behavior of people with ADHD, yet it is difficult to draw a mean-
ingful conclusion from those findings because of the varied con-
cepts and definitions of adherence used. There is a need to
standardize the literature by developing a consensus on the use of
the operational definition of medication adherence. The more
transparent conceptual model of adherence (ABC taxonomy)
proposed by Vrijens et al. (2012) should be considered for use in
future research. A consensus was built on this model in the 13th
European Consensus Meeting attended by participants from
around the world (Vrijens et al. 2012). The use of this conceptual
model will standardize the literature, provide a common platform
for comparing and combining health research, aid in the devel-
opment of tailored interventions to improve medication adher-
ence, and promote health policy decisions based on consistent
scientific evidence.
Variability in the definition of adherence phases in the literature
has increased ambiguity in research findings. Despite a growing
 16
number of studies measuring adherence and examining factors
influencing medication adherence in patients with ADHD, the
ambiguity in research findings has halted the development of ad-
herence research in ADHD population, which is evident by the lack
of evidence-based intervention to improve medication adherence at
its three phases. Standardization of adherence research using a
common taxonomy and conceptual definition of adherence and its
phases is important for the development of adherence research in
ADHD.
Factors affecting medication adherence
This review found that while there are common factors that
affect the three phases of adherence, there are also factors that are
unique to each of the three phases of adherence. Studies in other
disease populations have also identified different determinants for
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each adherence phase (Gillespie et al. 2017; Jensen et al. 2017). The
primary reason for differences in factors affecting different phases
of adherence is a clear distinction in the dynamics of the three
phases that change over time. This needs to be given serious con-
sideration while planning interventions to improve adherence and
long-term medication outcomes for people with ADHD. More
studies are required to investigate the influencing factors based on
the phases of adherence.
The review also found variation in the factors within each phase
of adherence based on the population being studied. For example,
parental factors affecting initiation of medication were consider-
ably different from the factors affecting the initiation in other
groups. This finding is supported by other studies that have reported
different barriers to adherence between children, adolescents,
adults, and parents (McQuaid et al. 2003; Buchanan et al. 2012).
Medication adherence among children presents unique challenges,
which are different from those in adolescents and adults. The role
of parents becomes crucial in this group as parents are mainly
responsible for making health decisions. As children grow into
adolescents they start to take responsibility for their own medica-
tions; however, parents still play an important role in this group.
Growing awareness and physical, emotional, and cognitive chan-
ges present unique circumstances in adolescents compared to
children and adults. To develop effective interventions, it is es-
sential to identify unique adherence barriers impacting different
groups in the population.
It is noteworthy to highlight the parental factors that affect med-
ication initiation. Involvement of parents in the treatment process is
essential for the successful management of ADHD (Swanson 2003).
Therefore, it is essential to provide them information about the dis-
order, its management, and the likely side effects of medications
(Ghanizadeh 2007) so that they can make informed decisions about
the use of medications (Swanson 2003). Lack of knowledge leads to
negative attitudes and beliefs of parents toward the disease and its
management (Schommer 1990). This review found that the negative
beliefs about medication and fear of side effects among parents were
major obstacles toward achieving optimum medication adherence.
These findings have potential implications for both clinicians and
researchers. Parents visit clinics with the expectations that their
children’s condition will improve. However, negative beliefs about
the medication may affect their medication-giving behavior and
contribute negatively to medication adherence. This indicates the need
for interventions to improve patients’ understanding of the disease and
the medication. One possible intervention could be the provision of
education to parents about their children’s symptoms and medications
(Ferrin and Taylor 2011).
KHAN AND ASLANI
In contrast, age, gender, and psychiatric comorbidity were the
common factors that affected medication initiation in children and
adolescents. It is worthwhile highlighting the issue of treatment
consideration in people with ADHD and psychiatric comorbidities.
Some studies have reported that improvements in comorbid psy-
chiatric symptoms could be achieved with effective treatment of
ADHD (Spencer et al. 2006; Adler and Nierenberg 2010), which
therefore could facilitate adherence. On the contrary, there is also a
risk that stimulants (which are the first-line options for ADHD) may
lead to mood destabilization in patients with bipolar disorders
(Bond et al. 2012), which could lead to reduced adherence or
treatment cessation if experienced by the patient or not initiating
treatment if the patient or parent believes in the possibility of mood
destabilization occurring. This review shows that psychiatric co-
morbidities may increase the initiation of ADHD medication. This
is likely due to more adverse behavioral outcomes in patients with
comorbidities compared to people with ADHD alone (Cuffe et al.
2015) and, therefore, more likely for ADHD treatment to be initi-
ated if positive psychiatric symptoms are expected. However, due
to a limited number of studies, there is a need for further research in
this area. Inconsistencies in findings were observed regarding the
effect of gender on medication adherence, making it difficult to
provide specific recommendations regarding the effect of gender on
medication initiation in people with ADHD. This finding is in line
with other studies that explored the effect of gender on medication
adherence in other psychiatric and nonpsychiatric disease states
(Ahmed and Aslani 2014).
Although more than half of the studies examined factors af-
fecting the implementation phase of medication adherence, the
results were not consistent. Inconsistencies in reported factors were
not only observed between different groups (parents, children,
adolescents, and adults) but also were apparent between the studies
within the same population. Similarly, inconsistencies were ob-
served for the discontinuation phase of adherence. However, it is
of great importance to discuss the highly variable effects of
gender on discontinuation. The possible reasons for the effect of
gender were not mentioned in the individual studies; however, the
literature suggests that factors contributing to the differences
could be related to how adult males and females cope with the
burden of managing a chronic disease (Nau et al. 2007). The
evidence suggests that adult female patients often use inappro-
priate coping strategies due to their impulsive nature, which for-
ces them to make an ill-thought decision than their peers (Rucklidge
2010). It is quite possible that their ability to misjudge the situa-
tion because of their impulsiveness may affect their medication-
taking behavior. With regards to other disease states, studies have
reported lower adherence among females with diabetes and car-
diovascular complications, but the reasons for these differences
have remained a source of speculation (Pittman et al. 2011).
Theories have been put forward such as complexity of regimen,
out-of-pocket expenses, appearances of side effects, social ex-
pectations, and priorities to explain the effect of gender on med-
ication adherence (Manteuffel et al. 2014), but more studies are
needed to understand the complicated quagmire of gender-related
medication adherence in ADHD. Medication effectiveness was
the common factor that affected the discontinuation of medication
in all groups. These results are in accordance with previous
studies in different disease states in which treatment effectiveness
was linked to medication adherence (Osterberg and Blaschke
2005; Brunner et al. 2009; Brown and Bussell 2011). These
findings support the importance of following up patients to ensure
the effectiveness of medication and hence its adherence (Kav et al.
 FACTORS INFLUENCING ADHERENCE TO ADHD MEDICATION
2008; Jimmy and Jose 2011). However, it is important to under-
stand that the effectiveness of medication in ADHD depends very
much on dose optimization. If not tailored according to patients’
needs, it either results in a suboptimal response or may lead to side
effects ( Jensen 1999).
Gaps in the literature and future research
This review did not find any study that evaluated the factors
affecting initiation of medications in adult patients with ADHD.
This could be due to the lower proportion of new diagnoses of
ADHD in adults (de Graaf et al. 2008). However, the prevalence of
ADHD in adults has increased by more than threefold in recent
times (Montejano et al. 2011), and perhaps more studies will be
conducted in the future. Initiation studies are also very limited
among children and adolescents. Although a good number of
studies have examined the factors affecting the implementation
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phase of medication adherence, inconsistencies in findings warrant
further research, in particular, the greater delineation between the
factors influencing parents alone and those that influence children
and adolescents directly and indirectly through their parents. In
view of the relatively higher prevalence of ADHD in Australia
(Graetz et al. 2001), limited data are available regarding adherence
to medications. There is a significant need to bridge the knowledge
gap in this area. The findings of this review suggest that future
studies should examine the factors influencing adherence at each of
the three phases of adherence. Within each phase, factors should be
differentiated between parents, children, and adults as each popu-
lation may have unique influencing factors. Moreover, future
studies should examine the instruments/measures that can be used
to measure adherence at each phase.
Limitations
The findings of this review should be considered in view of
some limitations. Although an effort was made to improve the
methodological rigor, no statistical techniques were used to
synthesize the data due to the narrative nature of this review.
Caution should be exercised while generalizing the findings of
this review due to heterogeneity in designs, adherence measures,
and definitions used in the selected studies. Although a number of
factors influencing medication adherence were identified in this
review, it is difficult to comment on the aggregate magnitude of
these predictors in people with ADHD. Most of the studies fo-
cused on implementation phase; therefore, more data are avail-
able about predictors of adherence at the implementation phase.
More than one-third of studies included children and adolescents
as participants. Although a critique of individual studies was
provided, no formal approach was undertaken to evaluate the
quality of each study. Despite our efforts to differentiate the
factors, there remains a possibility for overlap of the factors
between the age groups. Gray literature, unpublished studies, and
articles not written in the English language were not included for
pragmatic reasons. Although a comprehensive 2-phase review
process was executed for the selection of eligible studies, there is
a possibility that some relevant publications may have been ex-
cluded inadvertently. Since there is no consensus on the terms
used for adherence and its phases, the search was limited to the
concept of adherence, compliance, medication taking, and the
three phases of adherence (initiation, implementation, and dis-
continuation). This may have resulted in the omission of studies
that have used other terms like medication acceptability and
refusal.
17
Conclusion
This review found that factors influencing one phase of adher-
ence are relatively different from the ones affecting other phases,
while some overlap was also noted. Within each phase, different
factors were identified for parents, children, adolescents, and
adults, as well as factors that impact one or more groups.
Clinical Significance
The findings of this review should help health care profes-
sionals and policymakers plan targeted interventions to promote
adherence at each of the three phases of adherence and, for each
phase, tailored to the needs of people with ADHD and their
parents/carers.
Disclosures
No competing financial interests exist.
Supplementary Material
Supplementary Table S1
Supplementary Table S2
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