Review

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Sleep problems associated with

ADHD: a review of current
therapeutic options and
recommendations for the future
Michel Lecendreux and Samuele Cortese

CONTENTS
Sleep alterations associated
with medications used
to treat ADHD &
comorbid conditions
Restless legs syndrome
Excessive nocturnal
motricity
Sleep-onset insomnia
Sleep problems associated
with sleep-disordered
breathing
Sleep problems associated
with psychiatric
comorbidities
Expert commentary
Five-year view
Key issues
Financial & competing
interests disclosure
References
Affiliations

Author for correspondence

Centre Pdiatrique des Pathologies
du Sommeil, Hpital Robert Debr,
48 Boulevard Srurier,
75019 Paris, France
Tel.: +33 140 032 285
Fax: +33 140 032 235
michel.lecendreux@rdb.aphp.fr
KEYWORDS:
attention-deficit/hyperactivity
disorder, dopaminergic agonists,
melatonin, pharmacological
treatment, sleep

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In recent years, there has been a growing interest in sleep problems associated with
attention-deficit/hyperactivity disorder (ADHD). The etiology of these sleep problems is
multifactorial. In this paper, we review the current literature on the treatment of the most
common disorders or factors underlying sleep problems associated with ADHD. In
particular, we focus on the management of sleep problems associated with ADHD
medications, restless legs syndrome, excessive nocturnal motricity in sleep, sleep
disordered breathing, sleep-onset insomnia and psychiatric comorbidities associated with
ADHD. Given the paucity of randomized, controlled, double-blinded, placebo-controlled
studies, it is hoped that this review will encourage further methodologically sound studies
in order to be able to develop treatment guidelines.
Expert Rev. Neurotherapeutics 7(12), 17991806 (2007)

Attention-deficit/hyperactivity disorder (ADHD)

is among the most common childhood psychiatric disorders, estimated to affect 510% of
school-aged children worldwide [1]. According to
the Diagnostic and Statistical Manual of Mental
Disorders (DSM)-IV [2] and its updated version
(text revision [TR]) [3], ADHD is defined by a
persistent and age-inappropriate pattern of
inattention, hyperactivityimpulsivity or both.
An onset before the age of 7 years and impaired
functioning in two or more settings are required
for the diagnosis. The DSM-IV and DSM-IVTR define four types of ADHD: predominantly
inattentive, predominantly hyperactiveimpulsive, combined and not otherwise specified.
Hyperkinetic disorder (HKD) is a narrower
diagnostic category defined in the International
Classification of Diseases (ICD)-10 [4]. The
diagnosis of HKD requires the presence of all
three dimensions of inattention, impulsivity and
hyperactivity. Deficits in executive functions,
including inhibition, working memory, planning and sustained attention, are common,
although far from universal, in ADHD [5].
Impairing symptoms of ADHD may persist

10.1586/14737175.7.12.1799

into adulthood in up to 60% of cases [6]. Stimulants (e.g., methylphenidate [MPH] and
amphetamines, the latter not available in
Europe) are the first-line US FDA-approved
pharmacological treatment, followed by the
nonstimulant atomoxetine (ATMX) [7]. This is
in line with European guidelines for ADHD
and ICD-10 HKD [8,9].
It is well known that ADHD is frequently
associated with psychiatric and developmental
disorders such as oppositional defiant disorder
(ODD), conduct disorder, anxiety disorders,
depressive disorders, speech and learning disorders, developmental coordination disorder
and tic disorders [10,11]. Conversely, the association between ADHD and sleep disturbances has
been quite overlooked in the past. However, in
recent years, there has been a growing interest in
the relationship between ADHD and sleep.
From a theoretical point of view, the emerging
body of research in the field aims to gain a better insight into the neurophysiological mechanisms underlying the link between ADHD and
sleep disturbances. From a clinical standpoint,
the increasing number of studies reflects the

2007 Future Drugs Ltd

ISSN 1473-7175

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need for a more appropriate and complete management of

ADHD patients who present with sleep alterations. In clinical
practice, in fact, parent-reported sleep difficulties in children
diagnosed with ADHD are quite frequent. According to a
review of the literature by Corkum et al., 2555% of parents
complain of sleep problems in these subjects [12]. The most commonly reported sleep problems include: difficulty falling asleep,
bedtime resistance, night awakenings, restless sleep and difficulties wakening in the morning. The appropriate management of
these problems is of relevance for several reasons:
Sleep problems may represent a significant source of distress for
the child and/or the family. As stated by Laufer and Denhoff
more than 60 years ago, Generally, the parents of hyperkinetic children are so desperate over the night problems that the
daytime ones pale in significance [13]. Therefore, the management of sleep problems may significantly improve the quality
of life of children with ADHD, as well as their families.
Sleep disturbances may worsen ADHD symptoms and/or
associated mood disorders [14]. Therefore, the treatment of
comorbid sleep disorders and interventions targeted at ensuring adequate sleep may substantially improve daytime
ADHD symptoms.
Any sleep disorder that results in inadequate sleep duration,
fragmented/disrupted sleep or excessive daytime sleepiness
may cause problems with mood, attention and behavior.
Therefore, sleep disturbances may mimic ADHD symptoms
in children misdiagnosed with ADHD [14]. As a consequence,
symptoms of inattention, hyperactivity and/or impulsivity
may be improved or even eliminated with treatment of the
primary sleep disorder.
It has been correctly highlighted that sleep problems
reported by patients with ADHD are multifactorial [14], meaning that they may be ascribed to different underlying sleep disorders or factors associated with ADHD. Therefore, the appropriate management of sleep problems in patients with ADHD
is based on the correct identification and treatment of sleep
disorder(s) or alteration underlying these problems. In this
review, we focus on the treatment, with a particular emphasis
on pharmacotherapy, of the main sleep disorders or alterations
underlying the most commonly reported sleep problems in
patients with ADHD.
Sleep alterations associated with medications used to treat
ADHD & comorbid conditions
Medications for ADHD

nonstimulant ATMX. Bupropion, tricyclic antidepressants

(TCAs), -agonists and modafinil are also used [15].
Subjective and objective studies on the effect of stimulants on
sleep have produced mixed results [16]. While some investigators have reported polysomnographically determined lengthened total sleep time, increased sleep-stage shifts, increased

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number of rapid eye movement (REM) periods, elevated

indexes of REM activity and REM-period fragmentation, parent-reported longer latencies to sleep onset or higher rates of
insomnia in ADHD children treated with stimulants versus
controls, others did not confirm these findings [16]. It is difficult
to combine the results of these studies owing to different stimulant formulations, dose and dose scheduling. As for dose scheduling in particular, some studies assessed the effect of stimulants
given in two doses (morning and noon). Since stimulants are
associated with the so-called rebound effect (increase over
baseline values in ADHD symptoms when the medication
wears off ) [17], it is possible that sleep problems reported in
these studies may be associated with restlessness linked to the
rebound effect more than to the direct action of stimulants.
However, other studies using a third dose (to avoid the rebound
effect) did find a more significant sleep-onset delay in children
treated with stimulants versus untreated subjects [18,19]. Therefore, and also on the basis of clinical experience, it is possible to
conclude that stimulants may negatively impact sleep, either
due to a direct effect or a secondary rebound effect as the medications wear off. The vulnerability to these negative effects is
likely to be related to individual factors. As correctly pointed
out by Brown and McMullen, while some patients with
ADHD are able to get to sleep easily within just a few hours of
taking a dose of stimulant, others need an interval of 68 h [20].
As for the effect of ATMX on sleep, in a recent randomized,
double-blind, crossover study comparing the effect of MPH
(administered three-times daily) and ATMX (administered
twice daily) on the sleep of the children with ADHD, Sangal
et al. found that MPH increased sleep-onset latency significantly more than ATMX, considering both actigraphic and
polysomnographic data [16]. Moreover, both child diaries and
parent reports indicated a better quality of sleep (getting ready
in the morning, getting ready for bed and falling asleep) with
ATMX compared with MPH. Both medications decreased
night-time awakenings, but the decrease was greater for MPH.
Clearly, these results need to be replicated.
On the basis of the aforementioned effects of ADHD medications on sleep, a panel of ADHD experts proposed the
following strategies to deal with sleep alterations caused by
stimulants [21]:
Simply wait (generally insomnia caused by stimulants attenuates after 12 months);
Adjustment in dose or dosing schedules (e.g., avoid evening
stimulant dose);
Switching to another stimulant formulation (in our clinical
experience, different formulations of the same stimulant may
impact sleep differently);
Switching to another stimulant (there are some data suggesting that amphetamines may impact sleep more significantly
than stimulants);
Switching to a nonstimulant (e.g., ATMX or buproprion);
Add antihistamines, trazodone, mirtazapine or melatonin;
Use clonidine.

Expert Rev. Neurotherapeutics 7(12), (2007)

Sleep problems associated with ADHD

If, on the other hand, the impact on sleep is caused by a

rebound effect (rebound hyperactivity leading to sleep-onset
difficulties), in our, as well as in others clinical experience, giving a low dose of MPH in the late afternoon or evening could
be helpful. Doses in the late evening could also be considered if
the rebound effect persists. As noted more than 30 years ago by
Kinsbourne, if a hyperactive child wakes during the night,
giving him a stimulant should help him go back to sleep [22].
However, it is important to note that these suggestions are
not intended as guidelines and, at the present time given the
paucity of controlled studies, no evidence-based recommendation on the strategies to face the negative impact of stimulants
on sleep can be made. As for clonidine in particular, although
no controlled studies are available, in a systematic chart review
of 62 children and adolescents with ADHD treated with clonidine for their sleep disturbances, Prince et al. reported that 85%
of patients were considered to be much very much improved by
the National Institute of Mental Health global assessment of
improvement [23]. Night-time clonidine doses ranged from 50
to 800 g. Adverse effects attributable to clonidine treatment
were generally mild and occurred in 31% of patients. The most
common adverse effects included morning sedation and fatigue.
Of note, although inadequate data were available to assess vital
signs and ECGs systematically, there were no clinical symptoms
referable to hypotension or arrhythmia.
Medications used to treat comorbid conditions
Antidepressants

Antidepressants, such as selective serotonin reuptake inhibitors

(SSRIs), used to treat comorbid depressive disorders may alleviate sleep alterations linked to depressive disorders. However,
SSRIs may increase sleep-onset latency, cause daytime sedation
and suppress REM sleep [14]. Citalopram, a new SSRI, has been
reported to have fewer negative effects on sleep continuity [14].
Venlafaxine may cause sleep-onset difficulties and problems
maintaining sleep. The new agents nefazodone (not available in
Europe) and mirtazapine may cause significantly less insomnia
than other SSRIs, although their use may be associated with
daytime sleepiness [14]. TCAs, which are no longer the first
choice in the treatment of childhood depressive disorders, have
been associated with decreased sleep-onset latency and
decreased arousals during sleep stage transitions. However, they
may also increase daytime sleepiness (particularly, amitriptyline, doxepin and trimipramine) [14]. Therefore, if the clinician
feels that antidepressants contribute to sleep problems in
patients with ADHD, they should use antidepressants that do
not significantly impact on effect on sleep, such as nefazodone
or mirtazapine.
Antipsychotics & anticonvulsants

Antipsychotics and anticonvulsants, which are used to treat

aggression associated with ADHD when stimulants alone are
not effective, as well as comorbid bipolar disorder (BPD), may
have a sedative effect resulting in excessive daytime sleepiness,
decreased sleep-onset latency, increased sleep continuity and

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suppressed REM sleep [14]. Therefore, the clinician should

modify the doses of these medications if excessive daytime
sleepiness is a side effect.
Restless legs syndrome

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an irresistible urge to move the legs, which is often
accompanied by uncomfortable sensations in the legs or, less
frequently, other body parts. These sensations are relieved by
movement and are worse in the evening, or night, and at rest.
The diagnosis of RLS is based on the revised RLS criteria developed by the International Restless Legs Syndrome Study Group
(IRLSSG) [24]. Although RLS has been traditionally considered
a disorder of middle to older aged adults, several case reports
have shown that it may occur in childhood. However, children
may report RLS symptoms differently than adults, in part
because of their limited ability to describe RLS sensations.
Moreover, the clinical presentation of RLS may differ in children. Considering these particularities, the IRLSSG has proposed a set of criteria specific for childhood RLS [24]. Polysomnographically, RLS may be associated with periodic limb
movements in sleep (PLMS) in approximately 80% of patients,
both in adults and in children. (PLMS are defined as movements that occur in series of four or more lasting 0.55 s, have
an amplitude of a quarter or more of the toe dorsiflexion during calibration and are separated by intervals of 490 s.) RLS
per se and/or associated PLMS may lead to significant sleep
fragmentation. Therefore, RLS is a recognized, although sometimes overlooked, cause of insomnia. In a review of the literature completed in 2005, our group examined the available evidence on the relationship between RLS and ADHD [25]. We
concluded that a relationship between RLS and ADHD has
been reported in the literature, although available studies did
not include representative samples and state-of-the-art assessment of ADHD. Several hypotheses may explain the relationship between RLS and ADHD/ADHD symptoms: sleep disruption associated with RLS might lead to inattentiveness,
moodiness and paradoxical overactivity; or diurnal manifestations of RLS, such as restlessness and inattention, might mimic
ADHD symptoms.
Alternatively, RLS might be comorbid to idiopathic ADHD.
Subjects with RLS and a subset of subjects with ADHD might
share a common dopamine dysfunction. When associated with
ADHD, RLS symptoms may exacerbate ADHD symptoms or
cause a later onset of symptoms of ADHD. Moreover, we have
found that children with RLS may develop bedtime refusal,
probably because they associate bedtime with the occurrence of
the unpleasant RLS sensations. Parents may consider this
refusal as the expression of a general oppositional attitude,
ignoring the real cause of the childs behavior [26]. Therefore,
RLS may be overlooked in children with ADHD and oppositional behavior. By contrast, it is also possible that ADHD
worsens RLS symptoms. Chervin et al. noticed that adult
patients with RLS sometimes report that increased daytime
activity worsens their nocturnal symptoms [27]. In the study by

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Wagner et al., the RLS symptoms were more severe in RLS

patients with ADHD symptoms than in RLS patients without
ADHD symptoms [28]. Therefore, we suggest that clinicians systematically look for RLS in patients with ADHD, and look for
ADHD symptoms in patients with RLS.
With regard to therapeutic strategies for patients with both
RLS and ADHD, interestingly some case reports have shown
the efficacy of the dopaminergic agents levodopa/carbiopa, pergolide and ropinirole in children diagnosed with both ADHD
and RLS and treated previously with psychostimulants with limited efficacy or intolerable side effects [29,30]. However, to date,
the limited number of patients treated and the absence of double-blind, placebo-controlled, randomized trials do not allow
evidence-based recommendations for treatment to be made.
Excessive nocturnal motricity

Our group reported significantly higher levels of nocturnal

activity (measured using an infrared camera) in children with
ADHD compared with controls [31]. In our meta-analysis of
the literature, we concluded that the available evidence suggests that the amount of movement in sleep is higher in subjects with ADHD than controls [32]. Although one can suppose
that high nocturnal activity fragments sleep leading to sleep
disturbance, we found no significant differences in sleep variables between ADHD children and controls. Moreover, polysomnography data showed no significant difference between
the two groups. However, interestingly, it has been reported by
ourselves [33] and another group [34] that late afternoon MPH
doses reduce nocturnal activity and improve sleep quality by
consolidating sleep. Yet, while some studies have showed that
MPH three-times daily does not impact sleep [35] or causes
only a slight decrease in sleep duration [19], others have
reported that a third dose of MPH does worsen sleep [18,36].
Given these contrasting findings, late afternoon stimulant
treatment can not yet be recommended as a guideline for
ADHD patients with high nocturnal activity. Further research
to clarify this controversial issue is welcome. As stated by Jerome, It is a common clinical experience of clinicians treating
children with ADHD that on occasion a small dose of MPH
taken before bedtime can facilitate sleep. Although this is not
the case for all children with ADHD it seems to be a robust clinical finding, which is not well documented in the literature [37].
If a third dose of stimulant seems necessary to control evening
ADHD symptoms but worsens sleep, for some patients, reducing the dose of evening stimulant or anticipating its assumption
may be noteworthy.
Sleep-onset insomnia

Approximately a third of medication-free children with ADHD

experience chronic sleep-onset insomnia (SOI) [38]. It has been
demonstrated that medication-free children with ADHD and
SOI have a delayed evening increase in endogenous melatonin
levels. To date, one open-label study and two randomized,
double-blind, placebo-controlled studies have been conducted
to assess the efficacy and tolerability of melatonin for the

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management of SOI in children with ADHD. In the openlabel study, Tjon Pian Gi et al. investigated the effect of melatonin 3 mg given in the evening on insomnia in a sample of 24
children with ADHD [39]. The authors reported that immediately after the start of melatonin treatment, the subjects fell
asleep significantly earlier than before, varying between 15 and
240 min, with a median value of 135 min in the first week of
treatment. The long-term effect after 3 months was comparable
with the immediate effect after 1 week. Interestingly, immediate relapse of insomnia was reported twice when treatment with
melatonin had been forgotten during the study period and
twice after ending the study. Restarted use of melatonin
restored the positive effect. The major limitation of this study is
the design (open label), which does not allow a placebo effect to
be ruled out since measures were based on subjective reports
and no laboratory set-up was available.
The first randomized, double-blind, placebo-controlled
study on the efficacy and tolerability of melatonin was reported
by Weiss et al. [40]. Indeed, in this study, the authors assessed
the efficacy of sleep hygiene coupled with melatonin treatment
for initial insomnia in a sample of 27 stimulant-treated children
with ADHD aged 614 years. Subjects first received sleep
hygiene intervention; nonresponders were randomized to a
30-day double-blind, placebo-controlled, crossover trial of
melatonin 5 mg. It was found that sleep hygiene reduced initial
insomnia with an overall effect of 0.67; the effect size for melatonin was 0.6. Adverse events were generally mild; however,
two limitations of this study should be noted. First, given the
design of the study, it is not possible to infer if melatonin
would have been effective in the absence of sleep hygiene. Second, since there was no prescreening with polysomnography,
patients with undiagnosed primary sleep disorders may have
enrolled in the study.
The second controlled study was reported by Van der Heijden
et al. [38]. In fact, this was the first randomized, placebo-controlled trial to assess the efficacy and tolerability of melatonin in
medication-free children with rigorously diagnosed ADHD and
SOI. A total of 105 subjects with ADHD (aged 612 years)
received melatonin (3 mg/day if body weight <40 kg and
6 mg/day if body weight >40 kg). After 4 weeks of treatment
using actigraphy it was found that sleep onset advanced by 26.9
47.8 min with melatonin and was delayed by 10.5 37.4 min
with placebo (p < 0.0001). Moreover, total time asleep
increased with melatonin (19.8 61.9 min) compared with placebo (p = 0.01). However, paralleling the findings by Weiss
et al., despite the improvements in sleep, melatonin demonstrated no effect on behavior, cognitive performance and quality
of life; the number of adverse events did not differ significantly
between melatonin and placebo [40]. The most common adverse
events were headache, hyperactivity, dizziness and abdominal
pain. Follow-up at 2 years yielded the following adverse events
in seven of the 24 followed patients: bedwetting (n = 2), abnormal feces (n = 2), drowsiness (n = 2), dizziness (n = 1), sleepmaintenance problems (n = 1), skin pigment changes (n = 1)
and decreased mood (n = 1). The lack of polysomnographic

Expert Rev. Neurotherapeutics 7(12), (2007)

Sleep problems associated with ADHD

measures is a limitation of this study. Despite their limitations,

the aforementioned studies suggest that melatonin might be an
effective treatment for SOI in children with ADHD. However,
since data on the possible long-term effects, such as on the
gonadotropic system and onset of puberty, are not available, further evidence is needed before systematically recommending
melatonin for SOI in children with ADHD.
Considering that a delayed evening increase in endogenous
melatonin levels might explain SOI in children with ADHD,
some authors investigated the efficacy of light therapy (LT). In
an open trial, Ryjak et al. administered 3 weeks of morning
bright LT to 29 adults with ADHD [41]. They found a significant phase advance in circadian preference, as well as a significant improvement in both subjective and objective measures of
ADHD. To our knowledge, no controlled study has been conducted to assess the efficacy of LT in patients with ADHD.
Moreover, with the exception of a recent case report [42], no
studies are available for pediatric age. Therefore, we think that
research in this field should be encouraged.
Sleep problems associated with sleep-disordered breathing

The relationship between sleep-disordered breathing (SDB)

and ADHD is still unclear. Several studies showed an association between SDB and ADHD symptoms [43,44]. Since some of
these studies did not use standardized ADHD criteria, it is
unclear whether SDB may be associated with ADHD symptoms or full ADHD (i.e., ADHD diagnosed according to
standardized criteria). However, the results of a meta-analysis
by our group including studies using rigorous criteria for
ADHD suggested that mild SDB may indeed be associated
with full ADHD [32].
With regard to treatment strategies, Huang et al. conducted
a controlled study in 66 children with ADHD and an
apneahypopnea index of between one and five events/h [45]. A
total of 27 children were treated with MPH, 25 underwent a
adenotonsillectomy and 14 had no treatment. The surgical
and MPH groups improved more than the nontreatment
group. When comparing surgical and MPH groups, there was
a significant difference in the sleep disturbance on the questionnaire used in the study. Moreover, some variables measured during the daytime (including attention span) and the
test of variables of attention (TOVA) subscales (impulse control, response time and total ADHD score) improved more in
the surgical group than the MPH group. These promising
results should prompt further studies to assess the effectiveness
of surgery in patients with SDB and ADHD, both for sleep
disorders and for core ADHD symptoms. They also suggest
that appropriate recognition and surgical treatment of underlying SDB in children with ADHD might prevent long-term
stimulant treatment.

children with ADHD, including up to 50% for oppositional

disorder, 3050% for conduct disorder, 1520% for mood disorders, 2025% for anxiety disorders, 1025% for learning disorders, more than 25% for developmental coordination disorder and approximately 20% for tic disorders. Moreover,
Tourettes syndrome and, in adolescents, substance abuse may
also be comorbid with ADHD. Finally, although the validity of
an early-onset form of BPD is still debated, there is some evidence to support the notion that a subgroup of children with
ADHD may present with comorbid BPD. All of these disorders
might be associated with significant sleep disturbances.
ODD may be associated with limit-setting disorder, characterized by noncompliant behavior in response to parental
requests to get ready for bed, bedtime resistance and delayed
sleep onset. Although data are still limited and, in part, contradictory, subjective as well as objective alterations of sleep have
been reported in childhood depressive [46] and anxiety [47] disorders. Evidence on sleep problems associated with BPD is still
very limited, in part because the definition of pediatric BPD is
still under discussion. However, preliminary evidence suggests
that children who are at risk for pediatric BPD reported poorer
sleep efficiency and more awakenings after sleep onset, less
REM sleep and longer periods of slow wave than matched controls, as well as significantly more sleep problems, including difficulty initiating sleep, restless sleep, nightmares and morning
headaches, than controls [48].
As for Tourettes syndrome, available data suggest longer
sleep period time, longer sleep latency, reduced sleep efficiency, prolonged wakefulness after sleep onset, more time
awake and less sleep stage II, increased epochs with short
arousal-related movements, increased frequency of sleepwalking, night terrors, trouble getting to sleep and early awakenings [4951]. Interestingly, new data from Kirov et al. have
shown that sleep problems in ADHD plus tic comorbidity follow an additive model [50]. Moreover, clinical experience suggests that tiapride, which is used to reduce tics, has a positive
effect on SOI without decreasing daytime vigilance in many
children. Further controlled studies should explore this issue.
Finally, although evidence on the effect of substance abuse on
sleep in children and adolescents is limited, available data suggest a dose-dependent relationship between sleep problems and
use of illicit drugs, alcohol and cigarettes [52].
In consideration of the impact of comorbid disorders on sleep,
we suggest that patients with ADHD are systematically evaluated for psychiatric comorbid disorders, especially when sleep
problems are reported. Clearly, the appropriate treatment of
comorbid disorders may improve sleep, but the clinician should
keep in mind that some medications used to treat comorbid
disorders may indeed impact sleep negatively (e.g., SSRIs).
Expert commentary

Sleep problems associated with psychiatric comorbidities

As stated in the introduction, psychiatric comorbid disorders are

quite frequent in ADHD. It is estimated that psychiatric comorbidity is present in as many as two-thirds of clinically referred

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Although comorbid sleep problems may be very impairing for

children with ADHD and their families, surprisingly, methodologically sound studies on treatment strategies are still limited.
With the exception of two recent studies on melatonin [38,40],

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no randomized, placebo-controlled studies are currently available. This seems to mirror the lack of strong evidence on the
pharmacological treatment of sleep disorders in the general
pediatric population. While the factors underlying some sleep
problems in ADHD (and their treatment) are currently receiving some attention (e.g., RLS or circadian rhythm disorder),
others deserve further investigation. For example, parasomnias
have been scarcely explored with objective methods in patients
with ADHD. Gaining insight into the impact of parasomnias
on sleep in this particular population could allow us to better
assess and treat factors underlying sleep problems in ADHD.
Another interesting topic is the role of iron deficiency in abnormal movement in sleep. According to some preliminary unpublished data by our group, iron deficiency might be involved in
the pathophysiology not only of RLS, but also of abnormal general movements, which may fragment sleep, thus impacting its
quality. If these data were confirmed by further studies, trials
with iron supplementation would be noteworthy. Moreover, the
interesting issue of the relationship between ADHD and primary disorders of vigilance/narcolepsy is still scarcely explored.
In our meta-analysis of the literature, we concluded that subjects with ADHD present with higher daytime sleepiness than

controls [32]. However, the relationship between narcolepsy and

ADHD has not been adequately studied. A pathophysiological
link between ADHD and narcolepsy/excessive daytime sleepiness suggests that studies on the effectiveness of wake-promoting agents (i.e., modafinil, an -noradrenergic agent) for
patients with ADHD and excessive daytime sleepiness should
be conducted.
Five-year view

In the coming years, multisite, randomized, controlled studies

should be conducted to provide stronger evidence on the
pharmacological treatment of sleep problems in ADHD,
enabling the development of practice guidelines. Further studies should confirm the efficacy of melatonin for sleep-onset
delay, as well as its long-term tolerance in children and adolescents, in particular regarding potential concerns on pubertal
development. Moreover, it is unclear how long melatonin
should and can be used. Further controlled studies are also
needed on the dopaminergic agents in order to determine their
efficacy and tolerance in children before recommending this
class of drugs in future guidelines. As for stimulants, we believe
that pharmacogenomic studies might be of interest in order to

Key issues
In clinical practice, 2555% of parents complain of sleep problems in their children referred for attention-deficit/hyperactivity
disorder (ADHD) symptoms.
The appropriate management of sleep disturbances in children referred for ADHD might significantly reduce their symptomatology
and improve their quality of life. The accurate management of sleep problems might also significantly improve symptoms of
inattention, impulsivity and hyperactivity in patients referred for a diagnosis of ADHD but who, actually, do not present full
Diagnostic and Statistical Manual of Mental Disorders criteria.
The etiology of sleep complaints in patients with ADHD is likely to be multifactorial. The following factors or conditions may
contribute to sleep disruption: medications for ADHD, comorbid psychiatric disorders, restless legs syndrome (RLS), excessive
nocturnal motricity, idiopathic sleep-onset insomnia and sleep-disordered breathing.
The appropriate management of sleep complaints in patients with ADHD is based on the identification and treatment of the
underlying disturbance or condition.
Dose or scheduling adjustment or switching to another class of medication are usually appropriate strategies to face sleep problems
associated with ADHD medications.
The appropriate nonpharmacological and pharmacological treatment of psychiatric comorbidities (avoiding medications known to
affect sleep) may significantly improve sleep problems.
Some case reports have shown the efficacy of the dopaminergic agents (levodopa/carbiopa, pergolide and ropinirole) in children
diagnosed with both ADHD and RLS and treated previously with psychostimulants with limited efficacy or intolerable side effects.
Two randomized, placebo-controlled studies have proved the efficacy and good tolerability of melatonin for sleep-onset insomnia.
Surgical treatment may significantly improve sleep quality in patients with ADHD and comorbid sleep-disordered breathing.
Further research is welcome on the effective treatment of sleep complaints in patients with ADHD; in particular, randomized
controlled studies are needed.
The interesting issue of the relationship between ADHD and primary disorders of vigilance/narcolepsy is still scarcely explored; a
pathophysiological link between ADHD and narcolepsy/excessive daytime sleepiness would suggests that studies on the
effectiveness of wake-promoting agents (such as modafinil, an -noradrenergic agent) for patients with ADHD and excessive
daytime sleepiness should be performed.

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Sleep problems associated with ADHD

better understand why some, but not all, patients do not tolerate an evening dose of MPH. Although, presently, this still has
a pure research interest, it could have interesting practical
implications in the near future. Further studies are also needed
on nonpharmacological treatment strategies (i.e., behavioral
therapy, surgery for SDB and LT for SOI). Studies assessing the
combination of nonpharmacological and pharmacological
treatments are also welcome. Research on new molecules
should also be encouraged in light of the advances in the potential pathophysiological mechanisms underlying sleep alterations
and ADHD. Such research might lead to more etiological treatments for both sleep alterations and ADHD symptoms. For
example, the finding that a subgroup of ADHD children have
primary excessive daytime sleepiness suggests that controlled
studies on the effectiveness of wake-promoting agents, such as
modafinil, to better treat excessive daytime sleepiness should be
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Biederman J. Attention-deficit/
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www.future-drugs.com

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involved in a randomized controlled trial assessing the effectiveness and tolerability of mazindol, a tricyclic compound that acts
as a central stimulant. All this body of research should help elaborate useful guidelines for the clinician who faces the challenge
of sleep problems associated with ADHD.
Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement

with any organization or entity with a financial interest in or
financial conflict with the subject matter or materials discussed in
the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents
received or pending, or royalties.
No writing assistance was utilized in the production of this
manuscript.

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Affiliations

Michel Lecendreux, MD
Centre Pdiatrique des Pathologies du Sommeil,
Hpital Robert Debr, 48 Boulevard Srurier,
75019 Paris, France
Tel.: +33 140 032 285
Fax: +33 140 032 235
michel.lecendreux@rdb.aphp.fr

Samuele Cortese, MD
AP-HP, Child and Adolescent Psychopathology
Unit, Robert Debr Hospital, Paris VII
University, Paris, France; Child Neuropsychiatry
Unit, GB Rossi Hospital, Department of
Mother-Child and Biology-Genetics,
Verona University, Verona, Italy
Tel.: +33 140 032 263
Fax: +33 140 032 297
samuele.cortese@gmail.com

Expert Rev. Neurotherapeutics 7(12), (2007)

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