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SLEEP PROBLEMS IN CHILDREN AND A

SLEEP PROBLEMS IN CHILDREN AND ADOLESCENTS WITH ATTENTION DEFICIT HYPERACTIVITY DISORDER: A CLINICAL UPDATE

1 Avinash De Sousa, 2. Aruna Kurvey

Consultant Psychiatrist & Psychotherapist Desousa FoundationMumbai, 1 Prof and Head Department of Psychology SL Raheja College Mumbai.2

 

 

Abstract

Recent evidence has been accumulating that the sleep of  individuals with attention deficit hyperactivity disorder (ADHD) is not only disrupted in a nonspecific way but that ADHD has an increased association with simple sleep related movement disorders such as restless legs syndrome/periodic limb movements in sleep, rhythmic movement disorder, and parasomnias, such as disorders of partial arousal. In addition an increased association has been reported between ADHD, narcolepsy and sleep apnea as well as circadian rhythm disorders, such as delayed sleep phase syndrome. These relationships are reviewed and the implications for such associations are explored. The implication of pharmacotherapy of ADHD on sleep problems is explained along with the effects of developmental and newer psychiatric comorbidity. It is prudent that patients with sleep disorders should be clinically questioned about the symptoms of ADHD and vice versa.

Key words: ADHD, Sleep disorders, Narcolepsy, Restless legs syndrome, Periodic limb movement disorder, Rhythmic movement disorder, Stimulants.

Introduction


Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioural disorders, with an estimated worldwide prevalence of approximately 5-15% in school-age children.1 Complaints of sleep problems in children with ADHD are common in clinical practice and are reported in 45-55% of cases.2 In the last decade, there has been a renewed interest in the relationship between ADHD and sleep disorders.3 Several groups have attempted to clarify the links between ADHD and sleep disorders. Research in this topic is relevant from a theoretical standpoint, suggesting possible novel etiopathophysiological models of ADHD as well as new insights into the effects of sleep alterations on behavioural and cognitive functions.4-5 The proper detection and management of sleep problems in children with ADHD may significantly reduce symptom severity and improve the quality of life of these children as well as that of their families.6 Indeed, it has been pointed out that any sleep disorder that results in inadequate sleep duration, fragmented or disrupted sleep, or excessive daytime sleepiness can lead to or contribute to problems with mood, attention, and behaviour.7

 

Critical Issue with Sleep Related Studies in ADHD

 

Researchers have studied sleep and alertness in children with ADHD using both subjective and objective measures. There have been studies based on questionnaires filled out by the children or their parents while others have used techniques such as polysomnography, actigraphy and the Multiple Sleep Latency Test (MSLT).8 Results from both groups of studies are highly inconsistent. Some researchers have reported significant differences between children with ADHD and controls, while many studies have failed to replicate these findings.9 These inconsistencies are often due different inclusion criteria used by these studies.10 There are also a few important reasons to account for the heterogeneity of sleep studies in ADHD.

First, there are marked differences in the evaluation methods for ADHD across studies, ranging from simple evaluation of symptoms of hyperactivity, impulsivity and inattention to a more rigorous application of different diagnostic criteria. Standardized and stringent diagnostic criteria are appropriate for a proper diagnosis of ADHD.11 The use of DSM-III criteria to assess the relationship between sleep problems and ADHD also has some limitations. DSM-III had included restless sleep as a defining characteristic of attention deficit disorder, and hence studies conducted with DSM-III criteria may have been confounded by the use of sleep disturbance as a diagnostic criterion12. Therefore, the use of DSM-III-R and DSM-IV criteria minimizes subject-selection bias.13 Second, only a few studies have excluded or controlled for the effects of psychiatric comorbidity. Comorbid disorders frequently associated with ADHD such as oppositional defiant disorder, depression and anxiety disorders may account for some of the sleep disturbances found in ADHD.14 It has been reported that depression with a childhood or adolescent onset may be associated with delayed sleep onset, problems with sleep maintenance, and excessive daytime sleepiness.15 Children and adolescents with anxiety disorders have also reported sleep-onset delay, problems with sleep maintenance, and sleep-related involuntary movements.16 Children with oppositional defiant disorder and conduct disorder too have clinically presented with difficulty in sleep onset in subjective studies.17 Psychiatric comorbidity may thus influence the results of the studies comparing sleep and alertness in children with ADHD versus control subjects.18

Thirdly, many studies on sleep issues in ADHD did not exclude or control for medication related factors and effects. Since pharmacological treatments for ADHD may affect sleep and alertness, it is preferable that one assesses non-medicated subjects to evaluate the relationship between sleep-alertness alterations and ADHD.19 Systematic reviews and meta-analyses on the subject have not been able to control for the above-mentioned potential confounding factors.20

It is possible that the difficulties reported as significantly higher in children with ADHD refer to inappropriate behavior in the context of problematic parent–child interaction and parents of children with ADHD may more likely report high levels of daytime and sleep-related problematic behaviours in a sort of a ‘negative halo effect’.21 Results from reviews on the subject do suggest otherwise. Results suggest that some of the parentally reported complaints about their children’s sleep may actually be due not only to inappropriate parent–child interaction but also to objective sleep disturbances.22 Another factors is the fact that that children with ADHD present with a night-to-night variability in sleep patterns.23 Therefore, it is possible that parents are more likely to recall and thus report as ‘typical’ those nights on which a child has significant bedtime resistance or difficulty falling asleep. It has been pointed out that sleep problems in ADHD are multifactorial i.e., they can be ascribed to many underlying factors. Therefore, the correct identification of such factors facilitates the appropriate management of sleep disturbances in this population.24 There have been reviews of sleep related problems in children and adults with ADHD but the present review restricts itself to ADHD in children and adolescents alone.

 

ADHD, Restless Legs Syndrome (RLS) & Periodic Limb Movements in Sleep (PLMS)

 

Restless legs syndrome (RLS) is a common 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.25 These sensations are worse at rest, relieved by movement, and worse in the evening or night and at rest. In RLS, patients frequently experience in­somnia from the leg discomfort and the need to move around.26 The diagnosis of RLS is based on the revised RLS criteria de­veloped by the International Restless Legs Syndrome Study Group (IRLSSG).27 Children may report RLS symptoms differently than adults, in part because of their limited ability to describe RLS sensations and it has been noted that the clinical presentation of RLS may differ in children.28

Patients with RLS also frequently have a related sleep dis­order called periodic limb movements in sleep (PLMS). PLMS are defined as movements that last 0.5–10 seconds and recur every 5 to 90 seconds in a series of ≥ 4.29 70-80% of adult patients with RLS have PLMS.30 PLMS have been reported in children with RLS although their prevalence in children has not been adequately studied.31 It has been correctly pointed out that sleep disturbances may mimic ADHD symptoms in the evening or be associated with ADHD symptoms.32 In these cases, the appropriate treatment of sleep disturbances may significantly improve diurnal ADHD symptoms. In a review of the literature, it was concluded that up to 44% of subjects with ADHD have been found to have RLS or RLS symptoms, and up to 26% of subjects with RLS have been found to have ADHD or ADHD symptoms.33 However, data should be considered with caution given some methodological limitations of the reviewed studies and it is probable that the real estimates of the prevalence of RLS in ADHD and vice-versa are more conservative.34 Further large epidemiological and clinical methodological studies are needed to assess the real prevalence of RLS (diagnosed according to standardized criteria) in children with ADHD (diagnosed according to DSM-IV criteria), as well as the prevalence of ADHD in children with RLS.35

Several hypotheses have been proposed to explain the association between RLS and ADHD (or ADHD-like symptoms). RLS associated sleep disturbance may cause inattentiveness, moodiness and paradoxical overactivity, thus mimicking symptoms of ADHD.36 Another hypothesis is that diurnal manifestations of RLS (who have been reported in children) mimic ADHD symptoms.37 Some children who are seriously affected with RLS cannot sit in school during the day for extended periods because they get up and walk around to relieve their leg discomfort. Hyperactivity might thus lead to inattention through the mechanism of leg discomfort in a subgroup of patients.38 In fact, true ADHD and RLS can be comorbid conditions.39 ADHD and RLS might share a common dopaminergic dysfunction.40 Since iron deficiency (which is a co-factor in dopamine synthesis) has been implicated into the pathophysiology of RLS41 and has also been reported in children with ADHD42, it has been suggested that iron deficiency is a common underlying pathophysiological factor to both RLS and ADHD. Genetic research in both RLS and ADHD are currently under investigation but no concrete evidence has been ascertained.43 Children with RLS can develop bedtime opposition, 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 child’s behaviour.44 It is also possible that ADHD worsens RLS symptoms.45 With regard to psychopharmacologic strategies for patients with both RLS and ADHD, some case reports have demonstrated the efficacy of low doses of dopaminergic agents (levodopa, pergolide, and ropinirole) in children diagnosed with both conditions who were previously unsuccessfully treated with psychostimulants.46 However, though dopaminergic agents are considered the first-line treatment for adults with RLS, they are not approved for use in children with RLS.47 No concrete evidence for iron supplementation as therapy has been noted in this group though some anecdotal reports exist.48

A number of studies have examined the relationship of ADHD to PLMS.49-51 A recent meta-analysis summarizing several such studies showed an intimate link between ADHD and PLMS.52 Since no randomized double-blind trials have been conducted to assess the potential effectiveness of the dopaminergic agents for ADHD and PLMS in children with both the conditions, this may represent a research avenue for the future. Moreover, since PLMS may improve after treatment with iron sulfate,53 in consideration of the possible role of iron in ADHD, it would be worthwhile to conduct randomized, placebo-controlled trials of iron supplementation for PLMS and ADHD.

 

ADHD, Narcolepsy and Daytime Alertness

 

Narcolepsy is characterized by excessive daytime drowsi­ness with or without sudden loss of body tone under conditions of strong emotion (cataplexy). Hypnologic hallucinations and sleep paralysis are frequently associated features.54 Arousals can be divided into phasic (tasks that require immediate attention) and tonic (tasks that require sustained attention). One of the glaring deficits in this area is that there has been no attempt to see if narcoleptic patients are also hyper­active. It is theoretically possible that narcoleptics move more in order to stay alert, but this has not been formally tested.55 ­More than a third of adults with ADHD are drowsy, as de­termined by a score >12 on the Epworth Sleepiness Scale ac­cording to one study.56 In ADHD patients, inattention scores correlated with the excessive daytime sleepiness scores. Of course, daytime drowsiness may be caused by disorders (such as sleep apnea) other than narcolepsy.57 To our knowledge, there is no study that systematically evaluates individuals with ADHD for the presence of either the MSLT findings of narcolepsy or secondary features of narcolepsy (sleep paralysis, hypna­gogic/hypnopompic hallucinations, or cataplexy).

To summarize, symptoms of inattention are com­mon in narcolepsy, but symptoms of hyperactivity in narco­lepsy need to be further explored. Drowsiness is common in ADHD, but the prevalence of narcolepsy in ADHD remains to be determined. The nature of excessive daytime sleepiness has yet to be determined: excessive daytime sleepiness might be a primary disorder or the consequence of some other sleep alteration.58 If excessive daytime sleepiness is actually a primary disorder in ADHD, these findings suggest new potential therapeutic strategies for a subgroup of children who present with ADHD associated with an alteration in sleep or wakefulness, and who may not respond adequately to first-line stimulant treatments, such as MPH and amphetamine salts.59 Wake promoting agents could be an important alternative to stimulants in these children. The use of the wake-promoting, non-stimulant agent modafinil has been proposed for this specific indication60, although the drug is not approved for this use. Double-blind studies should be conducted to evaluate the potential usefulness of this agent specifically in children with ADHD and excessive daytime sleepiness.

 

Sleep Disordered Breathing, Obstructive Sleep Apnea and ADHD

 

Obstructive sleep apnea (OSA) is characterized by relaxation of throat muscles during sleep and temporary obstruction of the airway for ≥ 10 sec. An apnea/hypopnea index > 30/hour is con­sidered severe and, over time, patients with OSA are possibly more subject to hypertension, heart disease, and stroke.61-62 A number of studies have examined the relationship between sleep disordered breathing and ADHD.63-64The possible mechanisms for the link between OSA and ADHD are sleep fragmentation and episodic hypoxia. Sleep disruption leads to non- restorative sleep that, together with intermittent hy­poxia or hypercarbia and the consequent disruption of cellular or chemical homeostasis, may induce alterations in the neurochemi­cal substrate of the prefrontal cortex.65 This in turn may result in executive dysfunction with adverse daytime effects such as poor planning, disorganization, rigid thinking, difficulty in maintain­ing attention and motivation, emotional liability, and over activity/ impulsivity.66 Another point in favour of this hypothesis are the improvements in behaviour, neuropsychological functioning, and sleepiness after treatment of sleep disordered breathing (SDB) .67 The results to date suggest that it is generally the milder forms of SDB that tend to be more common in ADHD children than in controls. This may be due both to the more frequent occurrence of milder as op­posed to more severe OSA in the pediatric community and to somnolence during the day in the severe cases, masking hyper­activity.68

There is a ‘primary’ ADHD with no OSA or other sleep disorders characterized by a reduced sleep frag­mentation at night (hypo arousal) and increased levels of day­time sleepiness on MSLT, and a ‘secondary’ ADHD, i.e., due to sleep disorders (OSA, PLMS), that, when treated result in improvement of the ADHD symptoms.69 To the best of our knowledge, no studies in obese children with ADHD have considered the effect of weight reduction on the symptoms of ADHD in parallel with the improvement of sleep disordered breathing.70 There is no mention of a parallel treat­ment effect on OSA for the non-stimulants used to treat ADHD, e.g. atomoxetine, bupropion, the α-2 adrenergic agents guanfa­cine and clonidine, tricyclic antidepressants, or modafinil.71

It is possible that OSA can cause mild inattention or hyperactivity, but it is still questionable whether children with a diagnosis of moderate to severe ADHD suffer from inat­tention or hyperactivity as a result of OSA. SDB may contribute to some mild ADHD-like symptoms that can be readily misperceived and may be the theoretical basis of overlap between the two diagnoses. Longitudinal and prospective studies evaluating the treatment effect of both the disorders may eventually clarify the relation­ship between OSA and ADHD.72 With regard to treatment strategies in this population, authors have reported that children with ADHD and an apnea–hypopnea index >1 and <5 events/hour improved significantly more after Aden tonsillectomy than after stimulant treatment.73-74 This suggests that appropriate recognition and surgical treatment of underlying SDB in children with ADHD might prevent the need for long-term stimulant treatment. A recent longitudinal study has shown that improvements are maintained 2.5 years after surgery.75

 

Circadian Rhythm Sleep Disorders in ADHD

Delayed sleep phase syndrome occurs primarily in adoles­cence and is characterized by sleep onset insomnia if the in­dividual tries to go to sleep early. In delayed sleep phase syndrome, the individuals with a propensity to sleep at a later time than normal is thought to be mediated through the biological clock located in the suprachiasmatic nucleus of the hypothalamus.76 ADHD seems to be characterized, in some cases, by a sleep onset insomnia characteristic of delayed sleep phase syndrome.77 On the other hand, the reverse relationship does not seem to hold, as a preliminary study suggests that ADHD symptoms are not common in delayed sleep phase syndrome.78 It may be that hyperactivity at night in ADHD causes a delayed sleep onset characteristic of Delayed Sleep Phase Syndrome, but that the sleep disruption from a delayed sleep onset is not enough to cause daytime inattention and hyperactivity charac­teristic of ADHD.79 It has been reported that medication-free children with ADHD and sleep-onset insomnia (SOI) exhibit a delayed evening increase in endogenous melatonin levels.80 Therefore, it has been hypothesized that SOI in ADHD is a circadian rhythm disorder due to a dim light melatonin onset delay.81 This may underlie and contribute to symptoms of bedtime discomfort with secondary resistance to go to bed, which may be erroneously considered as the expression of a general ‘oppositional-defiant disorder’.82

Considering that a delayed evening increase in endogenous melatonin levels might contribute to SOI in children with ADHD, some investigators have also assessed the effect of light therapy (LT) in this population.83 To our knowledge, no controlled study has been conducted to assess the efficacy of LT in children with ADHD, with the exception of a case report.84 It is noteworthy to report that, to date, pharmacological agents other than melatonin have not been found effective for sleep-onset insomnia in randomized controlled trials. In particular, a recent controlled trial85 reported that zolpidem at a dose of 0.25 mg/ kg per day to a maximum of 10 mg failed to reduce the latency to persistent sleep on polysomnographic recordings after 4 weeks of treatment in children and adolescents with ADHD.

 

Increased Nocturnal Motor Activity & Rhythmic Movement Disorder (RMD) in ADHD

 

Rhythmic Movement Disorder (RMD) primarily occurs in young children and is characterized by head banging or body rocking prior to sleep onset and sometimes during sleep itself. Most children outgrow the disorder. It is not truly considered a disorder unless sleep-related injury is present (which is uncom­mon), or daytime consequences related to reduced sleep quality are present. The disorder often disappears as children age.86 ADHD seems to be more common in RMD and, in turn, RMD seems to be more common in ADHD.87 The sample sizes tested are small, and results need to be confirmed in larger series. Whether sleep disruption from RMD leads to symptoms of ADHD, or whether a program for increased motor activity has a common diathesis in both RMD and ADHD bears further investigation.88 While some studies have showed that MPH three-times daily does not impact upon sleep89 or causes only a slight decrease in sleep duration90, others have reported that a third daily dose of MPH does worsen sleep. Given these contrasting findings, late-afternoon stimulant treatment cannot yet be recommended for ADHD patients with high nocturnal motor activity, and further research to clarify this controversial issue is welcome91.

 

Disorders of Partial Arousal and ADHD

 

Disorders of Partial Arousal (DOA) consist of complex be­haviours that are outside the conscious awareness of the individual. Patients with DOA are difficult to arouse and have little recollection of the events the next day. Subjects with DOA may walk (sleep walking or somnambulism- SW), talk in a confused way (Confusional arousals- CA) or run in a confused terror while screaming (Sleep Terrors- ST or Night Terrors- NT). Children usually outgrow DOA but DOA may recur in adulthood under conditions of emotional or physical stress.92-93 Despite scanty reports on Disorders of Partial Arousal in ADHD, this type of parasomnia seems to be quite prevalent in ADHD, and probably depends on chronic sleep deprivation via sleep fragmentation due to multiple arousals.94 Disorders of Partial Arousal frequently coexist with epilepsy but less so with nocturnal seizures.95 Levetiracetam exerts a positive overall effect not only upon epilepsy but also upon Disorders of Partial Arousal.96 The reverse prevalence, i.e., the prevalence of ADHD in Disorders of Partial Arousal remains to be studied.97

 

Psychiatric Comorbidity in ADHD and Sleep

 

Psychiatric comorbid disorders including oppositional disorder, conduct disorder, mood disorders, anxiety disorders, learning disability, developmental coordination disorder and tic disorder or Tourette’s syndrome are frequent in ADHD.98 Most of these psychiatric disorders might be associated with significant sleep disturbances, from a subjective and, less consistently, objective standpoint.99 One must systematically evaluate associated psychopathologies in patients with ADHD, especially when sleep problems are reported. The appropriate treatment of comorbid disorders may improve sleep, but the clinician should keep in mind that some medications used to treat these conditions may negatively impact sleep (e.g., selective serotonin reuptake inhibitors).100

 

ADHD Medications and Sleep

 

Psycho stimulants (methylphenidate, amphetamine salts and lisdexamfetamine dimesylate) are the first line, US Food and Drug Administration approved treatments for ADHD, followed by the non-stimulant atomoxetine (ATX). However, non-approved drugs, such as bupropion, tricyclic antidepressants, alpha-agonists and modafinil are also used.101 It has been suggested that stimulants used in the treatment of ADHD lead to sleep disturbances. In particular, it has been reported in some studies that stimulants have effects on sleep-onset delay102, night awakenings103, shorter sleep duration and dyssomnias.104 However; subjective and objective studies investigating the effects of stimulants on sleep in ADHD have produced mixed results. While some investigators have reported, among other outcomes, lengthened total sleep time, increased sleep-stage shifts, increased number of rapid eye movement (REM) sleep periods, elevated indices of REM activity, and REM-period fragmentation, others did not confirm these findings.105 As stimulant use may be associated with the so-called ‘‘rebound effect” (i.e., increase over base-line values in ADHD symptoms when the medication wears off) it is also possible that reported sleep problems may be linked with such restlessness rather than occurring as a direct action of the agents themselves.106

Regarding the effect of atomoxetine (ATX) on sleep in children with ADHD, in a recent randomized, double-blind, crossover study comparing the effect of MPH given three times daily and ATX given twice daily, it was  found that MPH increased sleep-onset latency significantly more than did ATX, considering both actigraphic and PSG data. Moreover, both child diaries and parental reports indicated a better quality of sleep with ATX compared with MPH.107 Both medications decreased night-time awakenings, but the decrease was greater with MPH. Clearly, these results need to be replicated in additional studies.

 

Future Research Needs

 

There is increasing evidence of alterations of sleep in children with ADHD, albeit at present there is still a lack of evidence on the most effective and safe treatment strategies (both pharmacological and non-pharmacological). Looking ahead, one of the most important issues in the research on the relationship between ADHD and sleep disturbances is to conduct methodological sound studies controlling for the possible confounding effects of psychiatric comorbidities and ADHD on sleep variables. Once we gain further insight in the relationship between ADHD and sleep, appropriate treatment strategies of sleep disturbances in subjects with ADHD should be systematically addressed. One research area which needs to be developed is represented by the effectiveness of behavioral strategies for sleep problems in children with ADHD.108

Moreover, since evidence on the effectiveness of some medications (such as dopaminergic agents for RLS) comes from single cases or case series, further large randomized controlled studies on the effectiveness and tolerability of medication for sleep disorders associated with ADHD are needed. Besides randomized controlled trials on the effectiveness of pharmacological and non-pharmacological treatments for sleep disturbances in ADHD, there are some under-explored areas of research. The interesting issue of the relationship between ADHD and narcolepsy or primary disorders of vigilance has yet to be fully explored. Another area of research which is still under-developed is the relationship between ADHD and parasomnias, which could provide important insights into the pathophysiology of ADHD and could suggest useful treatment strategies to improve sleep quality in ADHD.109 Finally, possible genetic underpinnings and neuroimaging correlates of the association between sleep disturbances and ADHD lay the ground work for fruitful and innovative avenues of research.110-111

 

Conclusions

 

ADHD symptoms occur frequently in the setting of several specific sleep disorders and vice versa. We would recommend that clinicians be aware of the potential connection between ADHD and the specific sleep disorders mentioned. We have two general recommendations. First, because the various sleep disorders mentioned more frequently have symptoms of ADHD than control populations, we recommend that patients with these sleep disorders be queried about the symptoms of ADHD. Second, since ADHD patients more frequently have symptoms of the various sleep disorders in question, we also recommend that patients with ADHD be queried about the sleep disorders in question. If these sleep disorders are present in patients with ADHD, they should be addressed. In addition, there remains the possibility that treatment of the associated sleep disorder may lead to adjunctive improvement of the ADHD symptoms in conjunction with stimulant therapy. In addition to strengthening already established connections, future investigations should explore whether narcolepsy is char­acterized by paradoxical hyperactivity, whether ADHD patients have a higher prevalence of narcolepsy, and whether patients with DOA more frequently have ADHD symptoms.


 

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