Drug Holidays From ADHD Medication: International Experience Over the Past Four Decades

Abstract

Objective:
ADHD is managed by stimulants that are effective but can cause growth retardation. Prescribers should ideally monitor children and trial a "drug holiday" to enable catch-up growth. Our aim was to map the experience of drug holidays from ADHD medication in children and adolescents.

Method:
A comprehensive search of the literature identified 22 studies published during the period 1972 to 2013.

Results:
Drug holidays are prevalent in 25% to 70% of families and are more likely to be exercised during school holidays. They test whether medication is still needed and are also considered for managing medication side effects and drug tolerance. The impact of drug holidays was reported in terms of side effects and ADHD symptoms. There was evidence of a positive impact on child growth with longer breaks from medication, and shorter breaks could reduce insomnia and improve appetite.

Conclusion:
Drug holidays from ADHD medication could be a useful tool with multiple purposes: assessment, management, prevention, and negotiation.

Full text

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Journal of Attention Disorders
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DOI: 10.1177/1087054714548035
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Kinda Ibrahim and Parastou Donyai
Drug Holidays From ADHD Medication: International Experience Over the Past Four Decades
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Article
Introduction
ADHD is characterized by hyperactivity/impulsivity and
inattention, and is one of the most common psychiatric
childhood conditions, affecting 3% to 6% of school-age
children in the United Kingdom (National Institute of
Health and Care Excellence [NICE], 2013). The condition
is associated with many potential medical, emotional,
behavioral, social, and academic consequences (NICE,
2006). Usually the treatment of ADHD is multi-disciplinary
involving medical, behavioral, and educational interven-
tions. The short-term effectiveness of stimulant medication
such as methylphenidate and amphetamines in controlling
the core symptoms of ADHD and enhancing cognitive
function and academic performance among children and
adolescents with ADHD are well documented (DuPaul,
2006; Hechtman et al., 2004; Pietrzak, Mollica, Maruff, &
Snyder, 2006; Wilson, Cox, Merkel, Moore, & Coghill,
2006). However, the long-term effects (either positive or
negative) of using stimulant medication among young
patients with ADHD are not yet well documented. In addi-
tion, the short-term adverse events associated with stimu-
lants can be very harsh for patients and their families.
Research has shown a possible relationship between using
stimulants and reduced growth of children with ADHD.
Two review studies have linked stimulant use with decreases
in height and weight especially during the first years of
treatment (Poulton, 2005; Rapport & Moffitt, 2002).
However, one other study that monitored the weight and
height of 89 ADHD children over 3 years reported a low but
not significant reduction in weight gain and no effects on
the ultimate growth. The author of this study suggested that
despite the possible negative effects of stimulants on
growth, the benefits of medical treatment outweighed the
growth-related side effects (Zachor, Roberts, Bart, Isaacs,
& Merrick, 2004). However, clinicians are asked to monitor
closely and regularly the height and weight of children who
are treated with stimulants usually every 6 months to mini-
mize the side effects and avoid undesirable events, and to
take any necessary arrangement where needed (NICE,
2013; Taylor et al., 2004). One of the recommended arrange-
ments if child growth is affected is to plan a break from
medication as referred to as a “drug holiday” (van de Loo-
Neus, Rommelse, & Buitelaar, 2011). NICE states,
548035JADXXX10.1177/1087054714548035Journal of Attention DisordersIbrahim and Donyai
research-article2014
1University of Reading, UK
Corresponding Author:
Parastou Donyai, University of Reading, Whiteknights House, Reading
RG6 6AP, UK.
Email: p.donyai@reading.ac.uk
Drug Holidays From ADHD Medication:
International Experience Over the Past
Four Decades
Kinda Ibrahim1 and Parastou Donyai1
Abstract
Objective: ADHD is managed by stimulants that are effective but can cause growth retardation. Prescribers should ideally
monitor children and trial a “drug holiday” to enable catch-up growth. Our aim was to map the experience of drug holidays
from ADHD medication in children and adolescents. Method: A comprehensive search of the literature identified 22
studies published during the period 1972 to 2013. Results: Drug holidays are prevalent in 25% to 70% of families and are
more likely to be exercised during school holidays. They test whether medication is still needed and are also considered
for managing medication side effects and drug tolerance. The impact of drug holidays was reported in terms of side effects
and ADHD symptoms. There was evidence of a positive impact on child growth with longer breaks from medication, and
shorter breaks could reduce insomnia and improve appetite. Conclusion: Drug holidays from ADHD medication could
be a useful tool with multiple purposes: assessment, management, prevention, and negotiation. (J. of Att. Dis. XXXX; XX(X)
XX-XX)
Keywords
ADHD, drug holiday, medication, children, adolescents
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2 Journal of Attention Disorders
If growth is significantly affected by drug treatment (that is, the
child or young person has not met the height expected for their
age), the option of a planned break in treatment over school
holidays should be considered to allow “catch-up” growth to
occur. (2013, pp. 36-37)
A drug holiday refers to “the deliberate interruption of
pharmacotherapy for a defined period of time and for a
specific clinical purpose” (Howland, 2009, p. 1). NICE
guidelines in the United Kingdom and guidance by the
American Academy of Child and Adolescent Psychiatry
(AACAP) in the United States recommend intentional
breaks from medicine-taking (drug holidays) to test the
continuing need for therapy in children and adolescents
with ADHD (AACAP, 2007; NICE, 2013). AACAP guid-
ance recommends “patients should be assessed periodi-
cally to determine whether there is continued need for
treatment or symptoms have remitted. Treatment of ADHD
should continue as long as symptoms remain present and
cause impairment” (AACAP, 2007, p. 913). This guideline
states that clinicians should discuss the continuing need
for medication with patients and their parents if the patient
with ADHD has been free of symptoms for at least 1 year.
Signs of remissions that could warrant consideration of
planned drug holidays include the following: patient has
been stable on the same dose for a prolonged period of
time, ability to concentrate during previous drug holidays,
and lack of deterioration when medication is missed.
School holidays are good opportunities to withdraw the
medication; however, parents should purposefully assign
cognitively demanding tasks (reading a book, practicing
mathematical problems) to test that remission has
occurred. If symptoms of ADHD recur and affect child
functioning at school and home, then doctors are advised
to return the child to medication. The evidence that backs
up advice relating to drug holidays is sometimes related to
the Multimodal Treatment Study of ADHD (MTA), which
showed that medication effectiveness can subside after 2
to 3 years of treatment (MTA Cooperative Group, 2004).
European clinical guidelines for hyperkinetic disorder
state, “If there are indications of growth retardation, drug
holidays (e.g. during the summer vacation) are recom-
mended” (Taylor et al., 2004, p. 16). In addition, in the
United States the Institute of Clinical Systems Improvement
(ICSI) recommends that linear growth impairment might
be managed by limiting stimulant to high-priority needs,
for example by trying weekend or vacation “drug holi-
days” (ICSI, 2012). Yet the European guidelines on man-
aging the adverse effects of medication for ADHD are not
in favor of applying drug holidays (Graham et al., 2011).
These guidelines suggest taking into account the “the
risk–benefit balance of drug holidays.” Moreover, they
report that to date, and despite their theoretical benefits,
the evidence that drug holidays can help control side
effects is very limited (Graham et al., 2011).
The NICE guidelines do not routinely recommend drug
holidays but instead they emphasize finding a best pattern
of use, which can include periods without drug treatment.
However, it is not often clear whether drug holidays are sys-
tematically considered and introduced in children and ado-
lescents with ADHD and what their real impact is, which
provides the rationale for the current article. The attitudes
toward and the outcomes of interrupting ADHD medication
taking among children and adolescents could have an
impact on the practice of drug holidays. Given that no
reviews have been published that address the recorded
experience of “drug holidays” from ADHD medication, the
purpose of this review is to map the practice and impact of
periodical breaks from medication among children and ado-
lescents with ADHD. The specific aims of this review are to
outline the prevalence of ADHD drug holidays among chil-
dren and adolescents, explore the reasons for ADHD drug
holidays, and extrapolate the impact of ADHD drug holi-
days in this patient group.
Method
Information Sources and Searches
A comprehensive search of the published literature was
conducted to identify all studies that had examined the
uptake of or attitudes toward “drug holidays” from ADHD
mediation in children and adolescents. From January to
March 2013 (with a supplementary search in January 2014),
Medline and PsycINFO academic databases were searched
for articles published between 1970 and 2013 on this sub-
ject. The aim of this review was to map the experience of
ADHD drug holidays since the introduction of medication
for this condition; therefore, the search period extended
back four decades. In addition to the academic databases
listed above, the search engine Google Scholar was used in
an attempt to capture studies published online, which were
not at first identified by the more traditional means. The
reference lists of all important articles were also scanned to
check for other relevant studies that may have been missed
via database searching.
A variety of search terms was constructed for use within
the databases, including attention deficit disorder (ADD)
with hyperactivity (MeSH term), withholding treatment
(MeSH term), medication adherence (MeSH term), patient
compliance (MeSH term), drug holiday(s), treatment inter-
ruption, medication continuation, medication discontinua-
tion, treatment continuation, treatment discontinuation,
treatment cessation, medication cessation, treatment drop-
out, prescriptions, and prescribing. These terms were com-
bined suitably according to the databases used. A number of
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Ibrahim and Donyai 3
additional terms potentially portraying drug holidays from
ADHD medication were later identified through the articles
retrieved and these were additionally inputted into the data-
bases, but did not increase the yield of articles: trial off
medication, trial without medication, break from medica-
tion, temporary medication cessation, medication vacation,
structured treatment interruption, intentional non-adherence,
and time on and off medication. The details of the search
and retrieval strategy are outlined in Figure 1.
Study Selection
The title and abstracts of all articles initially identified (384)
were scanned after duplicates (22) were removed. Studies
of any design that had examined the reasons for, the preva-
lence of, or the impact of drug holidays from ADHD medi-
cation among children and adolescents patients published
from 1972 to 2013 were included for initial review. A total
of 63 articles were selected for full text assessment from
which 15 were included in this review. Additional 7 articles
were identified by searching reference lists of retrieved
articles and Google Scholar search. So a total of 22 research
articles were included eventually in this review. We chose
to include articles with different epistemological bases
because we wanted to gain in-depth information about the
practice of “drug holidays” among children and adolescents
with ADHD, which could include qualitative as well as
quantitative data.
384 citations after
duplicates removed
Records excluded
because they were
judged not relevant
(n=321)
Full-text articles
assessed for eligibility
(n=63)
Full-text articles
excluded (n=48)
Full-text articles
included n=22
Medline (313
citations
identified)
PsycINFO (94
citations
identified)
The title and abstract of the
papers were screened for
potential eligibility.
The search terms were used to
identify potentially relevant
papers published in English
from 1972 to 2013
The full-text of each remaining
article was assessed for
eligibility. Studies that met the
following criteria were
included in the review: primary
research paper, peer reviewed
article, qualitative or
quantitative study, information
about drug holidays in ADHD ,
and age was limited to under
18.
Articles were excluded
because when examined the
full text had information
about non-adherence issues
but did not report on
temporary planned drug
holidays or the focus of the
study was on adults with
ADHD, or non-English
published paper .
Hand searching of the
reference lists of articles
retrieved and searching
Google Scholar identified a
further 7 research papers that
met the inclusion criteria but
were not published in journals
indexed in Medline and
PsycINFO.
Figure 1. The literature search strategy and identification of publications included in this review.
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4 Journal of Attention Disorders
Inclusion and Exclusion Criteria
The following inclusion criteria were used to select articles
for this review: primary research articles, qualitative or
quantitative study, studies that reported information about
drug holidays among patients aged between 6 and 18 years
old, and English language publication. Articles were
excluded if the focus was on treatment discontinuation per
se or non-adherence rather than brief temporary medication
cessation. Studies were also excluded if they were pub-
lished in a language other than English and if the focus was
on adults with ADHD rather than children and adolescents.
Data Abstraction, Appraisal, and Synthesis
The articles included in this review were analyzed in line
with qualitative review methodology (Donyai, Herbert,
Denicolo, & Alexander, 2011) to produce a number of
themes that reflect published knowledge about ADHD drug
holiday experience. A grid was created to record summaries
of the articles for conceptualization and construction of the
literature review. This initial tabulation presented informa-
tion on study characteristics including the year of study, the
study sample, country where research took place, research
design, and a brief description of study aims (see Table 1).
The full text of all included articles was reviewed and any
information about drug holidays was extracted for further
analysis. Data from articles included in the review and
relating to the experience of “drug holiday” from ADHD
medication were grouped into three categories: prevalence
of ADHD drug holidays, outcomes of ADHD drug holi-
days, and reasons for ADHD drug holidays.
The quality of the studies was evaluated with criteria
based on those established by Hawker, Payne, Kerr, Hardey,
and Powell (2002). The critical appraisal tool consists of a
nine-item checklist to evaluate the quality of both qualita-
tive and quantitative studies. Accordingly, to assess the
quality of the studies, for each article the title and abstract,
introduction and aims, method and data, samplings, data
analysis, ethics and bias, results, transferability and gener-
alizability, and implications and usefulness were all indi-
vidually rated as either good (g), fair (f), poor (p), or very
poor (vp) before returning a total score for each of these
rating categories relating to that article (see Table 2). The
scoring system then allowed comparison of articles so that,
for example, a study scoring “g = 7, f = 1, vp = 1” could be
judged of better quality against one scoring “f = 4, p = 3, vp =
2.” The quality of the included studies in this review varies
widely. The aim of this review was to capture a wide and
practical picture of the experience of drug holidays from
ADHD medication. Therefore, all studies were included
even those judged to be of low quality but interpreted care-
fully in the discussion. The majority of the studies contrib-
uted something new and added a novel perspective to the
practice of drug holiday.
Results
Twenty-two studies met the criteria for inclusion in this
review and were therefore selected for analysis. No system-
atic reviews were identified. The methodology that had
been adopted in the articles included quantitative research
(using, for example, surveys, clinical trials, and review of
prescription rates) as well as qualitative research (using
focus groups or interviews). Out of the 22 studies included,
17 research articles followed the nomothetic approach to
knowledge construction using different quantitative meth-
ods, whereas only 5 studies followed the idiographic
approach to knowledge construction using interviews and
focus groups techniques. It is interesting to note that only 4
studies (Brinkman et al., 2009, 2012; Bussing & Gary,
2001; Hazell, McDowell, & Walton, 1996) in total actually
referred to guideline recommendations about drug holidays,
3 of which were qualitative studies (Brinkman et al., 2009,
2012; Bussing & Gary, 2001).
The findings were grouped into three categories: preva-
lence of ADHD drug holidays, outcomes of ADHD drug
holidays, and reasons for ADHD drug holidays.
Prevalence of ADHD “Drug Holidays”
The practice of drug holidays from ADHD medication
among children and adolescents is a relatively common
phenomenon according to the research identified. The
majority of studies (13) included in this review provided
information on the prevalence of drug holidays from ADHD
medications by reporting either on uptake by parents or
practice by doctors (see Table 3). Anything from 25% to
almost 60% of families (with an average of 43%) surveyed
in 6 of these studies appear to skip medication administra-
tion at some point during the treatment course especially at
weekends and summer holidays (see Figure 2; Barnard-
Brak, Schmidt, & Sulak, 2013; Dosreis et al., 2003; Faraone,
Biederman, & Zimmerman, 2007; Hugtenburg et al., 2005;
Snyman & Truter, 2012; Wilens et al., 2005). The main
source of information about utilizing drug holidays in these
studies was parents of children and adolescents with ADHD.
This was confirmed by a study that examined prescription
data among patients with ADHD who were on a medical
treatment monthly for 4 years (Cascade, Kalali, Weisler, &
Lenderts, 2008). This study revealed a seasonality pattern in
prescribing methylphenidate among children and adoles-
cents with ADHD, as the total volume of ADHD medication
prescriptions decreases between May and July by almost
25%. This reflects a school-year-only dosing pattern
adopted by some families who give their children the medi-
cation only during the school period and stop it during sum-
mer break.
A survey with 788 parents of children with ADHD
showed that 70% of children stop taking their medication at
some point; and only in 34% stopping the medication was
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Ibrahim and Donyai 5
Table 1. Summary of All Studies Included in the Review in Reverse Chronological Order of Publication Year.
Author(s) Year Study design Country Study sample Brief description of the study aim
Barnard-Brak, Schmidt,
and Sulak
2013 Survey The United States 259 parents of children with an
average age of 10.61 years
Examine medication vacations among children with
ADHD according to parent–child dyad
Snyman and Truter 2012 Survey South Africa 51 parents of children with an
average age of 10.27 years
Investigate the etiology, diagnosis, and treatment
of children and adolescents with ADHD in South
Africa
Brinkman et al. 2012 Focus groups The United States 44 adolescents aged 13 to 18
years
Gain a detailed understanding of how adolescents
with ADHD contribute to medication treatment
decisions
Wong et al. 2009 Interviews The United
Kingdom
10 clinicians and 15 adolescents
with ADHD aged between 15
and 21 years
Explore the process and outcome of medication
cessation to understand how cessation can be
appropriately managed
Brinkman et al. 2009 Focus groups The United States 52 parents of children with
ADHD aged between 6 and
17 years
Understand how parents make decisions about
treatment for their child or adolescent with
ADHD
Cascade, Kalali,
Weisler, and
Lenderts
2008 Prescriptions data The United States Patients with ADHD aged
between 0 and 18 years
Investigate the trends in ADHD prescribing
Skilling, Robinson, and
Fielding
2008 Survey Scotland 17 child and adolescent
psychiatry departments
Establish follow-up services available for children
and adolescents with ADHD and adherence to
guidelines
Faraone, Biederman,
and Zimmerman
2007 Open-label study The United States 407 children aged between 6
and 13 years
Analyze patient adherence to OROS
methylphenidate during a 1-year open-label study
Spencer et al. 2006 Open-label study The United States 170 children aged 6 to 13 years Investigate whether prolonged therapy with long-
acting stimulant affects growth in children with
ADHD
Pliszka, Matthews,
Braslow, and Watson
2006 Naturalistic study The United States 179 children with average age
of 9 years
Determine whether methylphenidate and mixed
salts amphetamine have different effects on
growth
Wilens et al. 2005 Open-label study The United States 229 children aged between 6
and 13 years
Assess the effectiveness and tolerability of
stimulants when used for prolonged periods in
children with ADHD
Rafalovich 2005 Interviews The United States 26 clinicians Investigate clinicians’ perceptions about the
diagnosis and treatment of ADHD
Hugtenburg et al. 2005 Pharmacy
dispensing data
The Netherlands 28 parents of children with
ADHD aged between 4 and
14 years
Gets insight into the compliance with medication in
children using methylphenidate
Martins et al. 2004 Double-blind
controlled
withdrawal study
Brazil 40 children aged between 6 and
14 years
Assess whether weekend drug holidays during
methylphenidate administration would change
drug efficacy and tolerability in children with
ADHD
Stockl, Hughes, Jarrar,
Secnik, and Perwien
2003 Survey The United States 365 clinicians Examine physicians’ perceptions of using medication
to treat ADHD in children and adolescents
Dosreis et al. 2003 Survey The United States 254 parents of children with
ADHD aged between 4 and
19 years
Assess parental attitudes and satisfaction with
stimulant treatment
Salmon and Kemp 2002 Survey The United
Kingdom
100 clinicians Identify the difference between CAMHS and
pediatric approaches to the assessment and
management of ADHD
Bussing and Gary 2001 Focus groups The United States 25 families of children with an
average age of 9.5 years
Examine parental evaluation of treatment
approaches to ADHD and their attitudes
regarding medication
Hazell, McDowell, and
Walton
1996 Survey The United
Kingdom
788 parents of children with
ADHD aged younger than
19 years
Examine the local procedures for assessment of
ADHD and its management with stimulants
Klein, Landa, Mattes,
and Klein
1988 Controlled
withdrawal study
The United States 58 children aged between 6 and
12 years
Examine the effects of methylphenidate withdrawal
on the growth of hyperactive children
Satterfield, Cantwell,
Schell, and Blaschke
1979 Prospective study The United States 72 children aged between 6 and
12 years
Examine the growth of hyperactive children treated
with methylphenidate
Safer, Allen, and Barr 1972 Controlled
withdrawal study
The United States 20 children with an average age
of 10 years
Examine the long-term effects of stimulant drugs on
indexes of growth in hyperactive children
Note. OROS = osmotic-controlled release oral delivery system; CAMHS = Child and Adolescent Mental Health Services.
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6 Journal of Attention Disorders
Table 2. The Quality Assessment of Studies Included in This Review.
Study
1. Title
and
abstract
2. Introduction
and aims
3. Method
and data 4. Sampling
5. Data
analysis
6. Ethics
and bias 7. Results
8. Transferability
and
generalizability
9. Implications
and usefulness
Total
score
Cascade, Kalali, Weisler,
and Lenderts (2008)
f p p vp vp vp f p f f = 4
p = 3
vp = 2
Hugtenburg et al. (2005) g f f p f vp g p p g = 2
f = 2
p = 4
vp = 1
Satterfield, Cantwell,
Schell, and Blaschke
(1979)
p vp g f f vp g f f g = 2
f = 4
p = 1
vp = 2
Pliszka, Matthews, Braslow,
and Watson (2006)
g g g g g vp g f g g = 7
f = 1
vp = 1
Bussing and Gary (2001) f g g g f g g p g g = 6
f = 2
p = 1
Spencer et al. (2006) g g g g g vp g f p g = 6
f = 1
p = 1
vp = 1
Stockl, Hughes, Jarrar,
Secnik, and Perwien
(2003)
g f g g g vp g f vp g = 5
f = 2
vp = 2
Brinkman et al. (2012) g p g g f g g f f g = 5
f = 3
p = 1
Brinkman et al. (2009) g p g g f f G f f g = 4
f = 4
p = 1
Salmon and Kemp (2002) p g f g f vp F f f g = 2
f = 5
p = 1
vp = 1
Skilling, Robinson, and
Fielding (2008)
f f f f p vp F f p f = 6
p = 2
vp = 1
Klein, Landa, Mattes, and
Klein (1988)
f f f g f vp F f vp g = 1
f = 6
vp = 2
Dosreis et al. (2003) f f g g g f G f g g = 5
f = 4
Barnard-Brak, Schmidt, and
Sulak (2013)
g g f g g vp F f p g = 4
f = 3
p = 1
vp = 1
Wong et al. (2009)
Faraone, Biederman, and
Zimmerman (2007)
g g g g g g G g g g = 9
g g g g g vp G p vp g = 6
p = 1
vp = 2
Hazell, McDowell, and
Walton (1996)
g f f g p vp G f vp g = 3
f = 3
p = 1
vp = 2
(continued)
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Ibrahim and Donyai 7
planned in order to test the real need for medication but the
length of the break was not mentioned (Hazell et al., 1996).
The length of and the reasons for drug holidays in the
remaining cases (36%) and whether the break from medica-
tion was planned or unplanned were not reported in that
published study.
Two open-label studies that evaluated the effects of
osmotic-controlled release oral delivery system (OROS)
methylphenidate among a combined total of 636 children
with ADHD documented that about (32%-40%) of
patients took drug holidays for a duration longer than a
week during the study period (Faraone et al., 2007; Wilens
et al., 2005). All patients in a third open-label study also
had “some” degree of a drug holiday during the study
course, with almost 29% of children taking drug holidays
≥30 days during 21 months of the study (Spencer et al.,
2006).
The use of different definitions of “drug holiday” among
the studies included in this review (see Table 4) could
account for the differences in the reported drug holiday
rates from ADHD medication. In some studies, not taking
the medication temporarily at weekends and/or during
school holidays is defined as a planned drug holiday,
whereas other studies had proposed more specific defini-
tions and considered any break from medication for at least
7 consecutive days as a planned drug holiday. Other studies
did not differentiate between planned and unplanned drug
holidays and considered any break from medication admin-
istration for more than 24 hr to be a drug holiday and this
was linked with the largest prevalence rate of 70%.
Furthermore, another possible reason for the differences in
the prevalence of drug holidays reported could be the data
collection method. Examining prescribing records revealed
a lower prevalence rate of drug holidays than questioning
parents of children with ADHD. This could be explained by
the fact that many parents will initiate drug holidays them-
selves without doctor involvement or even without report-
ing to their doctors. Therefore examining medical records
would not be enough to capture real experiences.
Doctors’ attitudes toward and consideration of regular
planned drug holidays were shown to vary culturally. A sur-
vey in the United States in 2003 with 365 prescribers of
ADHD medication indicated that only 30% of doctors agree
or strongly agree that drug holidays should be incorporated
in the medical regimen of children with ADHD (Stockl,
Hughes, Jarrar, Secnik, & Perwien, 2003). Whereas in the
same decade, in the United Kingdom and Scotland, around
60% of surveyed pediatricians and child and adolescents
psychiatrists said that they consider a trial without the medi-
cation on an annual basis (Salmon & Kemp, 2002; Skilling,
Robinson, & Fielding, 2008). These differences could be
due to culturally different views and beliefs of doctors about
ADHD medications which might in turn impact on their
attitudes toward drug holidays. The local guidelines and
recommendations about the management of ADHD could
also affect doctors’ practice of drug holidays. However, cur-
rently this is not the case because nowadays both British
and U.S. guidelines recommend that doctors consider peri-
odical breaks from ADHD medication among their patients.
The percentages reported in these surveys reveal only doc-
tors’ views about drug holidays but not their actual practice.
Doctors might discuss having a break from medication with
families but this does not guarantee parental agreement to
interrupt the treatment.
Study
1. Title
and
abstract
2. Introduction
and aims
3. Method
and data 4. Sampling
5. Data
analysis
6. Ethics
and bias 7. Results
8. Transferability
and
generalizability
9. Implications
and usefulness
Total
score
Snyman and Truter (2012) g f f p p f F p p g = 1
f = 4
p = 4
Wilens et al. (2005) g g g g f vp G f g g = 6
f = 2
vp = 1
Martins et al. (2004) g g g f g f G f g g = 6
f = 3
Safer, Allen, and Barr
(1972)
f f g f g vp G p f g = 3
f = 4
p = 1
vp = 1
Note. 1. Abstract and title: Did they provide a clear description of the study? 2. Introduction and aims: Was there a good background and clear statement of the aims of the
research? 3. Method and data: Is the method appropriate and clearly explained? 4. Sampling: Was the sampling strategy appropriate to address the aims? 5. Data analysis:
Was the description of the data analysis sufficiently rigorous? 6. Ethics and bias: Have ethical issues been addressed, and what has necessary ethical approval gained? Has the
relationship between research and participants been adequately considered? 7. Results: Is there a clear statement of the findings? 8. Transferability or generalizability: Are the
findings of this study transferable (generalizable) to a wider population? 9. Implications and usefulness: How important are these findings to policy and practice? Criteria: g =
good; f = fair, p = poor; vp = very poor.
Table 2. (continued)
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8 Journal of Attention Disorders
Attitudes Toward and Reasons for ADHD “Drug
Holidays”
Drug holidays from ADHD medication can be initiated either
by doctors or by parents and their children. A brief description
of the five qualitative studies included in this review is shown
in Table 5. The analysis of the results and the quotes identified
in these studies was grouped together into different themes
that reflect the reasons for considering drug holidays.
Is the medication still needed? There is ongoing dialogue
about the necessity of keeping children on the medication.
Therefore, some clinicians seem to consider drug holidays
from ADHD medication on an annual basis as standard
practice to test the continuous need for medication. As one
mother states in an article,
We have done this about every year, along with the paediatrician.
But he wants it to be consistent, normal time. Not over Easter
Table 3. Summary of the Included Studies That Report the Prevalence of Drug Holidays From ADHD Medication.
Study Study method Medication The main findings
Barnard-Brak,
Schmidt, and
Sulak (2013)
Survey — Almost 58.6% of parents of children with ADHD reported utilizing
drug holiday
Snyman and Truter
(2012)
Survey Methylphenidate
and
atomoxetine
Almost 53% of patients took drug holidays at weekends, while
approximately 59% went on drug holidays during school holidays.
About 24% went off the medication sometimes during weekends and
drug holidays
Skilling, Robinson,
and Fielding
(2008)
Survey — About 57% of the designated ADHD follow-up teams offer an annual
drug holiday as standard while it is only considered by 40% of
services where there is no ADHD follow-up team
Cascade, Kalali,
Weisler, and
Lenderts (2008)
Examining
prescribing
records
Methylphenidate There is seasonality in prescribing methylphenidate as evidence by the
finding that the total monthly prescription volume decreased from
22% to 29% between May and July for patients aged younger than 18
years
Faraone,
Biederman, and
Zimmerman
(2007)
Open-label
study
Methylphenidate
OROS
A total of 130 patients (31.9%) took drug holidays. In almost a quarter
of these children, the break was ≥30 consecutive days, whereas
the duration of break in the remaining children was from 7 to 29
consecutive days. Older children, minority ethnic groups, and those
with less severe symptoms are more likely to take medication breaks
and to have lower adherence to therapy
Spencer et al.
(2006)
Open-label
study
Methylphenidate
OROS
All children have some degree of drug holiday at some point. Almost
29% of children who participated in the study took drug holiday ≥30
days during 21 months of the study
And 71% reported to have a drug holiday less than 30 days
Wilens et al.
(2005)
Long-term
open-label
study
Methylphenidate
OROS
About 40% of children had a drug holiday more than 7 days. Almost
22% of them had a break for 7 to 29 days and the rest had it for a
longer time
Hugtenburg et al.
(2005)
Examining
pharmacy
records
Methylphenidate
IR
Almost 30% do not use methylphenidate at weekends, and 25% do not
use medication during holidays (2 weeks or shorter). Slightly more
than 30% do not use medications during summer holidays
Dosreis et al.
(2003)
Survey Methylphenidate
ER and IR
About 42% of parents give their children the medication only during
school days and 30% reported that they do not use medication at
school time and some non-school days
Stockl, Hughes,
Jarrar, Secnik,
and Perwien
(2003)
Survey Stimulants and
non-stimulants
Only 30% of doctors agree or strongly agree that drug holidays from
ADHD medication should be incorporated
Salmon and Kemp
(2002)
Survey — Almost 60% of the surveyed participants were reported to consider
trial without the medication on an annual basis
Hazell, McDowell,
and Walton
(1996)
Survey Stimulants Almost 70% of children who had been receiving medication for a year
will stop it at some time, but only in 34% stopping the medication
was planned in order to determine whether the medication is still
needed
Note. Dashes indicate that the medication type was not reported in the study. OROS = osmotic-controlled release oral delivery system; IR = immedi-
ate release formulation; ER = extended release formulation.
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Ibrahim and Donyai 9
break. Give it maybe a month or two off the medication to see
how it works. We have done it several times, and we have
always went back on the medicine. (Brinkman et al., 2009,
p. 585)
Parents also appear to use time on and off the medication
to see the effect for themselves and check the continuous
benefits of medication. Some parents may face a continuous
debate about whether to continue to medicate their children
driven by concerns about the adverse effects of ADHD
medication, which might make them question whether their
goals can be achieved without the medication. These trials
without the medication enable parents to clarify whether
they have to continue to medicate their children or not
(Brinkman et al., 2009). Some parents have been convinced
after a trial without the medication that their children need
to keep taking the medication, finding, for example, that
their child cannot function well at school without
medication:
We’d try to take her off and the teacher would write back, “What’s
going on? Behaviour is different, attention is different.” We tried
to see if the other stuff had kicked in . . . to see if the organizational
stuff had kicked in. (Brinkman et al., 2009, p. 585)
0
10
20
30
40
50
60
70
DH rate %
Summer DH %
weekend DH %
Figure 2. The different rates of “drug holidays” reported by parents of children with ADHD in the published literature identified as
part of this review.
Note. DH = drug holidays.
Table 4. The Different Definitions of Drug Holiday Across Some of the Studies That Reported the Prevalence of Drug Holidays.
Study Definition of a “drug holiday” Drug holiday prevalence
Snyman and Truter (2012) A drug holiday means having no or less
medication at weekends or school holidays
53% at weekend, 59% at school holiday, and
24% sometimes at weekends and school
holidays
Hugtenburg et al. (2005) A drug holiday means having no medication
at weekends and school holidays (such
as holidays less than 2 weeks or summer
holidays)
30% at weekends, 30% at summer holidays,
25% at school holidays less than 2 weeks,
and 25% to 30% use less medication at
weekends and school holidays
Faraone, Biederman, and
Zimmerman (2007)
A drug holiday means missing the medication
on ≥7 consecutive days
32% stopped the medication for more than
7 consecutive days
Wilens et al. (2005) A drug holiday means missing the medication
on ≥7 consecutive days
40% stopped the medication for more than
7 consecutive days
Barnard-Brak, Schmidt, and
Sulak (2013)
A drug holiday is defined as any period of 24
hr or more without the administration of
medication
58.6% took drug holidays
Dosreis et al. (2003) A drug holiday means having no medication
at weekends and school holidays
42% of parents reported undertaking drug
holidays over school holidays
Hazell, McDowell, and Walton
(1996)
A drug holiday refers to missing the
medication any time
70% of parents report missing the
medication at some point during the
treatment course
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10 Journal of Attention Disorders
Moreover, adolescents assume increased responsibility
for managing their health and especially medication tak-
ing as they grow up and mature. Adolescents with ADHD,
driven by their curiosity or rebellious nature, seem to
interrupt the medication themselves (Brinkman et al.,
2012). Trials without the medication seem to help adoles-
cents with ADHD to see how they would manage without
the medication. Thus, some adolescents get the confidence
to attempt a more prolonged period of cessation (Wong
et al., 2009) or in reverse they become convinced that they
really need the medication: “when I went off, I wanted to
see if I could be just ok without (medicine), my golf game
went to hell” (Brinkman et al., 2012, p. 15). The experi-
ence of drug holidays among adolescents with ADHD was
argued to be either a continuation of the medication usage
patterns adopted by their parents which involved having
regular breaks from medication or teenagers’ curiosity or
desire to rebel against their parents and doctors.
Managing medication adverse effects. Taking ADHD medica-
tions is associated with side effects such as sleep problems,
appetite suppression, and growth retardation (van de Loo-
Neus et al., 2011). Experiencing some medication side
effects lead some doctors to consider drug holiday, which is
seen a way of relieving the body from the unpleasant adverse
effects:
I will recommend a break from the meds if there is a consistent
lack of caloric intake. That is one of the common side effects,
lack of appetite. With the younger ones we have to really watch
them. We give them a break so they can eat normally and get
their caloric count on par with others their age. (Rafalovich,
2005, p. 316)
Parents’ concerns about the medication side effects also
result in some withholding medication at home and during
the holidays (Bussing & Gary, 2001). Moreover, drug holi-
days can come about as a result of intentional non-adherence,
which involves the child in smashing, hiding, or disposing
the medication. These breaks are initiated by patients them-
selves as a result of dislike of taking the medication due to
experiencing undesirable side effects (Wong et al., 2009).
Table 5. Summary of the Qualitative Studies Included in the Review.
Study
Method of data
collection Sample description The main findings
Brinkman et al.
(2012)
Focus group 44 adolescents aged 13
to 18 years
Many adolescents contrast trials on and off the
medication to test the continued efficacy of
medication. Some experimented over the summer
holidays so they did not have to jeopardize their
schoolwork
Brinkman et al.
(2009)
Focus group 52 parents of children
with ADHD aged
between 6 and 17
years
Parents contrast time on and off the medication,
which helped them inform decisions about
whether to persist with medication. Medication
was discontinued as a trial to see if the child still
benefits from the medication
Wong et al.
(2009)
Interviews 10 clinicians + 15
patients aged
between 15 and 21
years
Drug holidays at weekends and school holidays are
most suggested by clinicians or parents. Clinicians
prefer drug holidays to take place outside term
time to reduce any potential problems occurring
at school. Drug holidays could exhibit in a form
of intentional non-adherence such as smashing,
hiding, or disposing the medication. These breaks
are initiated by patients themselves as a result
of dislike taking the medication due to their side
effects
Rafalovich
(2005)
Interviews 26 physicians (GPs,
pediatricians,
psychiatrists, and
clinical psychologists)
The majority of clinicians recommend drug holidays
when the demands at school are not present.
Concerns about the medication adverse effects
and the development of drug tolerance make
doctors consider planned drug holidays
Bussing and
Gary (2001)
Focus group 25 parents of children
with an average age
of 9.5 years
Many parents reported school-time medication use
whereby stimulants are only administrated during
school days and withheld at home and in summer
Note. GPs = general practitioners.
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Ibrahim and Donyai 11
Management of drug tolerance. Drug tolerance, described as
a condition in which the effectiveness of medication is
maintained only through increasingly larger doses, is
another reason that was reported by some doctors for con-
sidering drug holidays from ADHD medication:
When tolerance is built up the drugs are far less effective and that
often means an increase in the dosage. It is better to allow the
child to take a break from the medication and let the body readjust
rather than to change the dose. (Rafalovich, 2005, p. 317)
Outcomes of ADHD “Drug Holidays”
The effects of having temporary breaks from ADHD medi-
cation were examined in seven research articles as outlined
in Table 6.
Effects of drug holiday on child growth. Five studies included
in this review examined the effects of drug holidays on
child weight and height and yielded different results. Three
studies reported a degree of advantages of summer drug
holidays on child growth (Klein, Landa, Mattes, & Klein,
1988; Safer, Allen, & Barr, 1972; Satterfield, Cantwell,
Schell, & Blaschke, 1979). Child’s height and weight were
measured and compared between two groups: those who
continued with medication during the summer holiday(s)
and those who stopped it. Safer et al. (1972) reported that
children who showed delays in height and weight when
treated with methylphenidate or dexamphetamine during
the school year experience accelerated growth rate when
medication is stopped during the summer. Children (on dex-
amphetamine) who discontinued the medication during the
summer experienced twofold increase in weight gain and
height velocity compared with those who continued on the
medication (Safer et al., 1972). The weight and height
velocity were, respectively, 68% and 15% more than
expected among children (on methylphenidate) who
stopped taking their medication during the 3 months sum-
mer. The other two studies examined the effects of two con-
secutive summer holiday drug holidays on child growth
(Klein et al., 1988). The first study reported that after two
summers of drug holidays from stimulant medication, sig-
nificant positive effects were reported on height but not on
weight. Children who were removed from medication dur-
ing the two summer holidays were significantly taller than
those who remained on it. The second study showed contra-
dictory results where significant positive effects for discon-
tinuing the medication during two summer holidays were
reported on children weight but not on their height (Satter-
field et al., 1979). The differences in reported findings could
be interpreted due to different factors such as individual dif-
ferences, the study design, the medication dosage, and the
initial baseline of child height and weight. Moreover, it
could be interpreted that the effects of stimulant medication
on height are not secondary to the weight reduction. The
length on treatment could also be a factor. None of the stud-
ies examined the possible link between how long children
with ADHD were taking their medication and the impact of
drug holidays on their growth. For example, some studies
had enrolled drug-naïve children who had never used
ADHD medication before, whereas others included chil-
dren who had already started taking medication before
entering the study.
Another two studies reported no significant impact of
having breaks from medication on child growth (Pliszka,
Matthews, Braslow, & Watson, 2006; Spencer et al., 2006).
Patients were allowed to have breaks from medication
themselves and all patients in the two studies were reported
to have taken some degree of drug holiday. One study con-
sidered any gap between visits and refills as a drug holiday
and reported that all patients have some degree of drug holi-
day at some point and that the length of drug holidays had
no impact on child growth (Pliszka et al., 2006). The other
study showed that almost 30% of patients took drug holi-
days lasting more than 30 days and 70% had less than 30
days without the medication, and no significant differences
in child height and weight were reported between these two
groups of patients (Spencer et al., 2006). Medication with-
drawal in both studies was not controlled but left optional to
families that participated in the study. Child growth was
compared between groups of patients who had different
degrees of drug holidays without using a control group
(e.g., “no drug holiday” group). So the results of these two
studies should be interpreted carefully because they may
not accurately capture the impact of drug holidays on child
growth. Differences in study design (controlled or uncon-
trolled), length, and whether or not breaks from medication
were consecutive could all account for differences in find-
ings in relation to child growth.
Effects of drug holiday on ADHD symptoms and medication side
effects. In addition to the four previous studies that exam-
ined the effects of drug holidays on child growth, two stud-
ies reported the impact of drug holidays on medication side
effects and symptoms of ADHD (Martins et al., 2004; Sny-
man & Truter, 2012). A double-blind controlled study with
40 children with ADHD compared the symptoms and medi-
cation side-effect profiles between two groups of children:
those who took drug holidays at weekends and those who
did not for 4 consecutive weeks. Rating scales to evaluate
ADHD symptoms and medication side effects were com-
pleted by teachers and parents. Weekend drug holiday was
reported to reduce insomnia and appetite suppression with-
out increasing the symptoms of ADHD (Martins et al.,
2004). Another study has shown that half of surveyed par-
ents of children with ADHD (about 25 out of 50 parents),
who had been on medication for an average of 16.7 months,
stop giving their children the medication at weekends and/
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12 Journal of Attention Disorders
or during school holidays. Those parents reported noticing
some changes in child symptoms during drug holidays at
weekends and/or during school holidays such as being more
active, less able to concentrate, more aggressive, and more
destructive (Snyman & Truter, 2012). At the same time, the
effect of drug holidays on child appetite was reported to be
low as only 9% reported that the appetite comes back when
medication is stopped at school holidays and weekends.
The findings of this study should be interpreted carefully
because no control groups were used to compare the
Table 6. Summary of the Studies That Examined the Impact of Drug Holidays on Medication Side Effects and/or ADHD Symptoms.
Study Design Measures used Study sample Medication
Drug holiday
length The main findings
Klein, Landa,
Mattes,
and Klein
(1988)
Randomized
controlled
withdrawal
study
Standard height
and weight
measures
58 children
aged 6 to 12
years
Methylphenidate Two
consecutive
summer
vacations
(3 months
each)
Summer drug holiday from
methylphenidate showed no
significant effect on children height
after the first summer, but after
two summers, children receiving
continuous methylphenidate were
1.5 cm shorter than those on drug
holiday. Weight did not differ
significantly between on and off
groups after the second summer
Spencer et al.
(2006)
Open-label
study for 21
months
Weight z
scores, height
z score, and
BMI z score
178 children
aged 6 to 13
years
Methylphenidate
OROS
30 days or
more within
21 months
Almost 29% of children who
participated in the study took drug
holiday ≥30 days during 21 months
of the study. And 71% reported to
have more than 30 days without the
medication. Drug holiday did not
reduce any impact of stimulants on
growth
Satterfield,
Cantwell,
Schell, and
Blaschke
(1979)
Prospective
study
Standard height
and weight
measures
72 children
aged
between 6
and 12 years
Methylphenidate Two
consecutive
summer
vacations
(3 months
each)
Children who did not take the
medication during the two summer
holidays had smaller height and
weight deficits during the second
year of treatment. This trend was
statistically significant for weight but
not for height
Safer, Allen,
and Barr
(1972)
Withdrawal
study
Standard height
and weight
measures
20 children
with an
average age
of 10 years
Methylphenidate or
dexamphetamine
3 months/one
summer
65% of children took drug holiday
during summer. Those children
gain more weight and height than
the other group who continue with
medication particularly those on
dexamphetamine and higher doses
of methylphenidate
Martins et al.
(2004)
Double-blind
study
Conners’
Abbreviated
Rating Scale
+ Barkley
Side Effects
Rating Scale
40 children
with ADHD
aged
between 6
and 14years
Methylphenidate 4 consecutive
weekends
Weekend holiday from
methylphenidate administration
reduces the side effects of insomnia
and appetite suppression without
a significant increase in symptoms
either in weekends or in the first
school day after them
Pliszka,
Matthews,
Braslow,
and
Watson
(2006)
Linear
regression
method
Height z score 179 Children
with ADHD
with an
average age
of 9 years
Methylphenidate Not specified All patients had some degree of drug
holiday either planned or unplanned.
Patients showed to miss their
medication for almost 32% of their
time. This study has not found any
effect of drug holiday on children
growth
Snyman and
Truter
(2012)
Survey Parents reports 51 parents
of children
with ADHD
Methylphenidate/
atomoxetine
Weekends
and school
holidays
Children are more active, less able to
concentrate, more aggressive, more
destructive during drug holidays.
The impact of drug holidays on
appetite is moderate as almost 9%
reported that the appetite comes
back
Note. BMI = body mass index; OROS = osmotic-controlled release oral delivery system.
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Ibrahim and Donyai 13
symptoms of ADHD or side-effect profiles. The effects of
drug holidays were obtained from questioning parents of
children with ADHD without being objectively verified.
Recall bias could also influence parents’ answers and
ratings.
Discussion
A total of 22 studies were examined in relation to the preva-
lence, the outcomes, and the reasons for ADHD drug holi-
days in children and adolescents. Prevalence data were
reported using different methods including parental sur-
veys, examination of medical records, and analysis of pre-
scribing data, and indicated that drug holidays are prevalent
in 25% to 70% of families and are more likely to be exer-
cised at weekends or during summer holidays in general.
But as well as being marred by different data collection
methodologies, articles reporting prevalence data did not all
report the length of the break, did not differentiate between
planned and unplanned breaks from medication, and used
different definitions of what constitutes a “drug holiday.”
Drug holidays were considered for different reasons,
namely, to test if medication was still needed (especially
with parents and adolescents), for managing persistent
medication adverse effects (for both parents and doctors),
and for managing drug tolerance (doctors only).
Qualitatively, some children returned to medication after a
drug holiday, whereas others did not and this was specifi-
cally true with adolescents. The impact of drug holidays
from ADHD medication was reported in terms of child
growth, other side effects, as well as impact on core ADHD
symptoms. Although there were weaknesses in the conduct
and reporting of some studies, there was evidence of a posi-
tive impact on child growth with longer breaks from medi-
cation during the summer holidays. In addition, shorter
breaks from medication exercised at weekends had the
potential to reduce sleep problems and improve appetite
with questionable results about whether or not the symp-
toms of ADHD intensify.
The practice of planned drug holidays with ADHD medi-
cation is acknowledged by many researchers interested in
measuring patients’ adherence to medication, who actively
take into account the experience of drug holidays in their
research (Charach, Ickowicz, & Schachar, 2004;
Thiruchelvam, Charach, & Schachar, 2001; Zhang, Du, &
Zhuang, 2010). These adherence studies show that adher-
ence rates to ADHD medications are higher when drug holi-
days are taken out of the equation. In the current review, all
planned drug holidays were found to be undertaken when
children are not at school, perhaps when the demands on the
child are lower. Certainly, studies show that behavioral and
attention problems among children and adolescents with
ADHD are mostly located within a school context (Evans,
2001) and medication such as methylphenidate is shown to
be very effective in improving children’s performance and
behavior at the school setting (DuPaul, 2006; Hechtman
et al., 2004). Therefore, understandably, worries about dis-
rupting children’s academic performance and upsetting the
balance of the school day could be the reason why drug
holidays from ADHD medication are mainly practiced out-
side of school days, at weekends, during summer, or other
breaks from schooling. A study reported a remarkable dis-
continuation of ADHD medication once young people reach
the age of 16 years for different reasons such as adolescents’
autonomy, feeling matured and not needing the medication
anymore, and experience with unpleasant medication side
effects (Marcus, Wan, Kemner, & Olfson, 2005). The
majority of clinicians in the study had experience of dis-
agreement between patients and their families on the issue
of cessation. Drug holidays from ADHD medication
appeared useful as a way of resolving conflicting ideas
about the need for continued medication.
Taking a drug holiday is a strategy that has been used to
manage side effects with a range of medication including
antiretrovirals (anti-HIV medication), bisphosphonates (for
osteoporosis), and antidepressants (Cohen, Colson, Sheble-
Hall, McLaughlin, & Morse, 2007; Curtis, Westfall, Cheng,
Delzell, & Saag, 2008; Rothschild, 1995). Similarly, in this
review it was found that worries about potential adverse
effects or the actual experience of side effects lead doctors,
parents, and adolescents to consider drug holidays from
ADHD medication. The impact of interrupting the medica-
tion on both the symptoms of ADHD as well as medication
side effects appears to depend on the length of the drug holi-
day, whether the days of the break are consecutive or not
and also which side effects are being measured. So, for
example, a significant increase in child growth is reported
with drug holidays taken during summer holidays, but not
with inconsecutive shorter breaks from ADHD medication.
However, there is some evidence that temporary withdrawal
of medication at the weekend can reduce side effects relat-
ing to sleep and appetite without increasing the symptoms
of ADHD. In the same vein, the benefits of taking drug holi-
days from antiretroviral drugs, such as reducing fatigue,
vomiting, nausea, and even toxicity, are linked to the length
of the drug holiday (eMC, 1999). In that situation, taking
the medication for 5 days and stopping for 2 days every
week was shown to be beneficial in reducing the toxicity of
antiretrovirals, while keeping the HIV suppressed (Cohen
et al., 2007).
Interestingly, the shorter breaks from medication with
antiretrovirals appear to be the only safe option because
when randomized clinical trials are conducted to assess the
benefits of long-term drug holidays the result is a worsening
of clinical outcomes in relation to immunological and viro-
logical status compared with continuous therapy (Strategies
for Management of Antiretroviral Therapy Study Group
[SMART], Lundgren, et al., 2008). So, while the longer
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14 Journal of Attention Disorders
drug holidays with ADHD medication appear to be benefi-
cial in terms of effect on child growth, none of the studies
included in this review documented the impact on clinical
symptoms, which might well be an important limitation of
these studies. It is important to measure clinical symptoms
because the perception of returning symptoms while on a
drug holiday can potentially result in children being put
back on ADHD medication without good reason. However,
measuring the symptoms of ADHD is not without its own
problems because there are no real clinical parameters to
measure apart from using rating scales, which can be sub-
jective. This is in contrast to many physical conditions
where the impact of drug holidays on disease progression
can be assessed objectively. So, for example, clinical
parameters such as bone mass density (BMD) measure-
ments are used to monitor the impact of bisphosphonate
drug holidays, and viral load and CD4 cell count are used in
HIV (Curtis et al., 2008; SMART, Emery, et al., 2008).
The development of drug tolerance and the need for
higher doses over time was reported in the literature as a
reason for planned drug holidays from ADHD medication.
The pharmacological treatment of Parkinson’s disease (PD)
with levodopa (L-DOPA) is also linked with the develop-
ment of tolerance to the medication. Research suggests that
taking a 7-day drug holiday from L-DOPA may re-sensitize
dopaminergic receptors and lower the patient’s L-DOPA
requirements, or at least prevent the need for increasing
L-DOPA dose in the near future (Corona, Rivera, Otero, &
Stopp, 1995). Stimulants’ ability to cause tolerance is con-
troversial, but certainly, the need for increasing the dose
over time has been reported in the literature. For example,
the AACAP guidelines state, “most children will need dose
adjustment upwards as treatment progresses” (AACAP,
2007). In addition, the MTA study reported that stimulants’
effectiveness subsides over time (MTA Cooperative Group,
2004). However, these specific sources do not directly sug-
gest the development of tolerance because dose escalation
could be due to adherence problems, inadequate dosage, or
wrong initial diagnosis.
However, other studies do suggest the idea of tolerance
more explicitly. Some studies suggest that after oral admin-
istration of methylphenidate, while the high concentrations
are maintained at the site of action in the brain, the effec-
tiveness on controlling behavioral symptoms dissipate. This
was suggested to be due to acute tolerance to medication,
which might be a result of an adaption response at the syn-
aptic level to the blockade of the dopamine transporter
(DAT; Swanson et al., 1999). Other research has suggested
that the need for higher doses of stimulants over time could
be as a result of changes in pharmacokinetics as children
develop, the natural worsening of the underlying illness
with time, or could be due to changes in the environment of
the child (Yanofski, 2011). The medication itself could also
worsen ADHD because dependence and tolerance have
caused “paradoxical decompensation” (Yanofski, 2011).
Here, the chronic use of stimulants can result in adaptive
physiological changes in the neurons of the central nervous
systems, resulting in delayed therapeutic effects, the devel-
opment of tolerance, and anecdotally the loss of therapeutic
effects during long-term treatment (Yanofski, 2011). Safer
and Allen (1989) reported that about 6% of children treated
with methylphenidate for 3 to 10 years developed tolerance
to the drug effect. They did not explain the reasons for
developing tolerance but suggested it could be due to physi-
ological mechanisms or possibly due to the development of
other co-morbidities that might reduce the therapeutic
response to stimulants over time (Safer & Allen, 1989). It
has been hypothesized that drug holidays from medication
could partially reverse the adaptive effects of chronic phar-
macological stimulation and re-sensitize neurons when
medication is restarted (Howland, 2009). One study sug-
gests that children with ADHD may initially manage with a
smaller dose when methylphenidate treatment is restarted
after a drug holiday (Davis & Sabir, 2009).
Implications
Although most prescribed medications should be taken con-
sistently to maintain their therapeutic effects, drug holidays
in children with ADHD can sometimes serve a useful pur-
pose. NICE guidelines do not recommend doctors to include
drug holidays routinely in the therapeutic regimens of their
children with ADHD but advise them to form an agreement
with parents and their children about the best pattern of use.
Apparently, from this review, a considerable percentage of
families incorporate planned drug holidays in their patterns
of medication use. The literature retrieved suggests that drug
holidays from ADHD medication among children and ado-
lescents are helpful rather than harmful. They could be a tool
for confirming the benefits of medication, helping verify the
need for medication, and checking coping without the medi-
cation. The qualitative data included in this review suggest
that a trial without the medication could also be a tool for
testing the feasibility of long-term medication discontinua-
tion. However, drug holidays could be helpful in convincing
adolescents or parents to continue taking medication while if
the medication is no longer needed, then drug holidays could
be useful in persuading parents that permanent cessation is a
viable option. Quantitative data suggest that short breaks
from medication could be a useful way of alleviating prob-
lems related to medication taking such as side effects and
drug tolerance. The NICE guidance (NICE, 2013) presents
experiences of some parents of children with ADHD in rela-
tion to using medication. As well as the published literature,
these descriptions also suggest that children may develop a
tolerance to ADHD medication with time. Therefore, we
believe that doctors who deal with children with ADHD
should consider planned drug holidays on non-school days
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Ibrahim and Donyai 15
with children who show a need to increase the dose of medi-
cation with time instead of increasing the dose continually.
This could, on one hand, help to prevent developing toler-
ance to ADHD medication and, on the other hand, it could
help avoid exposing children to side effects as a result of
increasing the dose. Longer drug holidays such as those
taken during the summer months could be helpful for pre-
venting or managing medication adverse effects on child
growth. Thus, a drug holiday from ADHD medication can be
a multi-purpose tool for assessing the need for medication,
preventing and managing problems related to medication,
and negotiating medication continuation or discontinuation
(see Figure 3). In this sense, planned drug holidays from
ADHD medication could be helpful and should be advised
and presented to some if not all families at some point in the
treatment of the child as a positive approach.
Study Limitations
The results of this literature review are subject to some limi-
tations. First, the experience of drug holidays was not the
primary focus in most of the studies retrieved, which meant
that these studies were not ideal for capturing the prevalence
of or attitudes toward drug holidays. Second, the aim of this
literature review was to encapsulate the whole documented
experience of drug holidays from ADHD medication since
the introduction of medication. Therefore, even low-quality
studies were included in this review if they met the basic
inclusion criteria. However, low-quality studies were inter-
preted carefully in the discussion and conclusion of this
review.
Conclusion and Future Work
The pattern of use recorded in the literature indicated that
planned drug holidays from ADHD medication among chil-
dren and adolescents are very common phenomena that
usually take place over the weekend or during school holi-
days. This comprehensive literature review explains the dif-
ferent implications of drug holidays from ADHD
medication. Moving forward, a common definition for what
constitutes a planned drug holiday from ADHD medication
would help standardize future research. Clearly, distin-
guishing between planned and unplanned drug holidays is
important for accurately reflecting the prevalence of drug
holidays. Planned intentional drug holidays should refer to
a break from medication for a specific purpose (managing
medication side effect, checking the continuing need for
medication, etc.) and can be initiated by doctors, parents, or
older children. Measuring the impact of long breaks from
medication on actual ADHD symptoms as well as medica-
tion side effect is necessary and could be achieved by con-
trolled withdrawal studies. Moreover, research could also
identify whether drug holidays should be considered for
any child with ADHD or whether there are specific cases
where drug holidays are more worthwhile and also the dif-
ferent factors that contribute to successful drug holiday
trials.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
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Assessmenttool
Drugholidayscould be useful to assess the
connuous need formedicaon andchild ability
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Prevenve tool
Drug holidays could be useful to manage the
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Managementtool
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Author Biographies
Kinda Ibrahim qualified as a bachelor of pharmacy in 2005. She
has worked in community pharmacy, research, and academia. She
obtained an MSc in Hospital and Clinical Pharmacy in 2008 from
Damascus University in Syria. This work forms part of her PhD at
the University of Reading where she is investigating the discon-
tinuation of medication in children and adolescents with ADHD.
Parastou Donyai is an academic, a pharmacist, and a psycholo-
gist with expertise in investigating medication usage and discon-
tinuation in a variety of conditions. She is associate professor of
Social and Cognitive Pharmacy and director of Pharmacy Practice
at Reading School of Pharmacy where she focuses on applying
psychological research methods to studying topical issues relating
to pharmacy practice.
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