Sleep and Adhd: a Review

By Bartholomew, Kristin; Owens, Judith

Attention deficit/hyperactivity disorder (ADHD), the most common childhood psychiatric disorder, affects between 5 and 10% of schoolage children in the United States.1 Approximately four times more boys than girls are diagnosed with ADHD; this finding may be partially due to referral bias, but probably also reflects a true gender difference. Although the clinical presentation varies somewhat with age and gender, the cardinal features of the disorder are both behavioral (hyperactivity, impulsivity) and cognitive (inattention, difficulty focusing, distractibility) in nature. Deficits in “executive functions” (e.g,., working memory, response inhibition), controlled by the prefrontal cortex, are also a hallmark of the disorder. Dysfunction in any of these areas can lead to social and family difficulties, academic underachievement, and impaired occupational functioning.2 In the majority (upwards of 60%) of children diagnosed with ADHD, functional impairment continues into adulthood.

Although a number of “objective” measures of inattention (e.g., computerized performance tasks (CPT)) may be helpful in the evaluation of a child with ADHD symptoms, the diagnosis remains essentially a clinical one. Positive identification of 6 out of 9 DSM-IV-R inattention or hyperactivity/impulsivity characteristics in two or more settings is required; ADHD subtypes include primarily inattentive (approximately 25%), primarily hyperactive/impulsive (15%) and combined (60%).3 Symptoms must be present before the age of 7, persist for at least 6 months, and significantly impair academic, social, or occupational functioning. Other important considerations are that the child’s symptoms are viewed in a developmental framework, (i.e., based on what is expected of others in the same age group and of the same cognitive level and evaluated in the context of the individual child’s cognitive potential.

Upwards of 65% of children with ADHD may have a co-morbid psychiatric disorder, such as oppositional defiant disorder (ODD; 40- 60%), learning disabilities (40%), anxiety disorders (30%), conduct disorder (14%), and chronic motor tic disorders (11%). ADHD may contribute to substance abuse disorders in adolescents and adults,4 although studies suggest that treatment with psychostimulants appears to mitigate, rather than increase, the risk of, substance abuse in ADHD. Co-morbid conditions complicate the diagnosis and treatment of ADHD, and many children with co-morbidities may benefit from additional psycho-social interventions.5

One of the more recently recognized co-morbid conditions in childhood ADHD is sleep disorders.5 Clinical experience suggests that sleep problems in children with ADHD are not only common, but may exacerbate symptoms of inattention and behavioral dyscontrol. Although precise figures are unavailable, a number of research studies have also suggested that sleep problems are a common co- morbid condition with ADHD.6 Some studies have assessed the prevalence of neurobehavioral deficits in clinical populations of children with diagnosed primary sleep disorders; the pediatric sleep disorders most frequently studied from this perspective are discussed below and are sleep disordered breathing conditions including obstructive sleep apnea (OSA) and snoring, Restless Legs Syndrome/ Periodic Limb Movement Disorder (RLS/PLMD) and narcolepsy.7 Conversely, other studies have examined the prevalence of sleep problems in pediatric populations identified with learning, behavioral, attentional, or academic problems compared to control populations.8 Finally, a number of studies which have examined the effects of both acute and chronic partial sleep deprivation (sleep restriction) in older children and adolescents under experimental conditions have documented relative deficits in a number of neurobehavioral and neurocognitive domains, including behavioral signs and subjective reports of sleepiness, attention, reaction time, memory, and problem-solving ability and creativity (so-called “executive” or higher level cognitive processes).9 For example, early rise times in fifth graders have been associated with self- reported difficulties in attention and concentration.10

ADHD AND PRIMARY SLEEP DISORDERS

Obstructive sleep apnea affects roughly 2% of children ages 3 to 7. 11 Adenotonsillar hypertrophy is considered the most prevalent risk factor in childhood, but OSA is frequently identified in children who are overweight and obese. Most pediatric studies have supported a similar range of deficits in children with ADHD and with sleep-disordered breathing (SDB) in terms of attention, memory, and executive functions, as well as an increase in subjective sleepiness and mood disturbance.12-15 A higher prevalence of parent-reported externalizing behavior problems, including impulsivity, decreased attention span, hyperactivity, aggression, and conduct problems has been frequently reported in studies of children with either polysomnographically-diagnosed OSA or symptoms suggestive of SDB, such as frequent snoring. Furthermore, studies which have looked at changes in behavior and neuropsychological functioning in children following treatment (usually adenotonsillectomy) for OSA/SDB have also documented significant improvement in daytime sleepiness, behavior, and academic performance post-treatment.1618 In addition to these more subjective reports of improvement, there were objective improvements in neuropsychological measurements of attention, vigilance and reaction time, and cognitive functions.

Alternatively, the prevalence of SDB symptoms in children with identified attentional, behavioral, and academic problems has also been examined. One sample of first graders performing academically in the lowest 10th percentile found a prevalence of 18% of significant SDB symptoms.17 Several recent reports have documented a significant increase in OSA symptoms specifically in children being evaluated for or diagnosed with ADHD, and have suggested that as many as 25% of ADHD diagnoses may be linked to symptoms of sleepdisordered breathing such as habitual snoring.14

Significant neurobehavioral consequences may also occur related to RLS/PLMD, and may present as symptoms of ADHD.19, 20 Restless legs syndrome (RLS) is characterized by what is often described as uncomfortable “creeping” or “crawling” sensations occurring primarily in the lower extremities and during periods of rest or inactivity (e.g.,, sleep onset), which are relieved by movement. There is frequently a familial component, and exacerbating factors include increased caffeine intake and iron deficiency (low ferritin). Although the prevalence of RLS in the pediatric population is unknown, approximately 10% of adults in the US has the disorder, and retrospective reports given by these adults suggest that symptoms (such as restless sleep and “growing pains”) frequently first appear in childhood. 21 Approximately 80% of patients with RLS also have repetitive rhythmic kicking movements of the lower extremities during sleep called periodic limb movements. RLS is a clinical diagnosis; the diagnosis of PLMD requires polysomnography to detect the characteristic rhythmic movements of the tibialis anterior muscle group and frequent arousals. The symptoms of RLS appears to reflect decreased dopaminergic activity. Furthermore, treatment of these children with dopamine antagonists has been shown to result not only in improved sleep quality and quantity, but also in improvement in “ADHD” behaviors previously resistant to treatment with psychostimulants.

IS SLEEP IN CHILDREN WITH ADHD “DIFFERENT”?

Studies of children with ADHD have largely used either parental (or self-report) surveys or polysomnography (PSG) to examine the relationship between sleep architecture, sleep patterns and behaviors, and sleep disturbances and ADHD. While results have been mixed and at times contradictory, some features of sleep in children with ADHD appear to be relatively consistent across studies. First, most of the “objective” studies have failed to find consistent significant differences in sleep architecture and patterns between children with ADHD and controls.22 Second, although actigraphy studies using lightweight activity monitors,23 which presumably capture more “naturalistic” sleep wake patterns across time (3 to 5 nights), have also failed to demonstrate striking, consistent differences between children with ADHD and controls on the typical actigraphic sleep parameters (sleep onset, sleep duration, sleep efficiency, night wakings), they have suggested there may be two other distinctive features of sleep in these children. Activity during sleep in children with ADHD has been shown to be higher in several actigraphy studies, both in terms of frequency and duration of movements; this finding is also supported by a study which utilized infrared video recordings to assess nocturnal movements in children with ADHD.24 Several more recent studies examined not only the average of the actigraphic sleep parameters across the 5 day monitoring period, which was not different from controls, but also the night-to-night variability.25 The authors concluded that the instability of sleep patterns in children with ADHD set them apart, and postulated that this variability might reflect a fundamental impairment in arousal regulation in ADHD.

Finally, somewhat counter-intuitively, these studies consistently suggest that childr\en with ADHD, although their sleep parameters are comparable, may actually be “sleepier” (as measured by the number and rapidity of sleep onsets on MSLT) than normal children.26, 27 This raises the intriguing possibility that ADHD is associated with hypo- rather than hyperirousal, and that, at least for some children with ADHD, hyperactivity is an adaptive behavior that counteracts the effects of underlying daytime sleepiness. This hypothesis also provides an explanation for the seemingly paradoxical effectiveness of psychostimulants in treating this disorder.

In contrast to studies which have utilized more objective measures, parental report studies have almost universally reported a high frequency of significant sleep problems in children with ADHD. These include difficulty falling asleep, night wakings and restless sleep, at prevalence rates and/or at levels of intensity that are generally two-three fold that of control group children.28, 29 More recent studies have suggested that many of these sleep disturbances may be attributable to either medication-related effects, primarily from psychostimulants, or from common psychiatric co-morbid conditions such as Oppositional Defiant Disorder, rather than to ADHD per se.30, 31

The etiology of sleep disturbances associated with ADHD in childhood, thus, is likely to be multi-factorial and to vary across patients. As noted above, several studies have suggested that pharmacologie treatment (primarily stimulants) side effects may play an important role;32 for example, one study demonstrated subjective parental perception of increased (threefold) severe sleep difficulties including sleep onset delay and night wakings in children on psychostimulants for ADHD. Stimulants increase the monoamines in presynaptic clefts by blocking reuptake of dopamme and norepinephrine and enhancing their release. 33,34 Results of studies assessing objective (PSG) measures of psychostimulant effects are more variable; some have demonstrated evidence of delayed sleep onset, shorter sleep duration, and delayed onset REM. Stimulants may also have a “rebound” effect when wearing off at the end of the day, resulting in an increase in arousal and hyperactivity above baseline.35

In addition to medication-related sleep effects, there appears to be an important influence on sleep behavior of such common co- morbid conditions as oppositional defiant disorder, depression, and anxiety disorders. Virtually all psychiatric disorders in children may be associated with sleep disruption as well as daytime sleepiness, fatigue, abnormal circadian sleep patterns, disturbing dreams and nightmares, and movement disorders during sleep. For example, sleep complaints, especially bedtime resistance, refusal to sleep alone, increased nighttime fears, and nightmares are common in children with anxiety disorders. Children with oppositional and defiant behavior may be more likely to demonstrate problems with limit setting and bedtime resistance. Conversely, growing evidence suggests that “primary” insomnia (i.e., insomnia with no concurrent psychiatric disorder) is a risk factor for later developing psychiatric conditions, particularly depressive and anxiety disorders.

However, the question remains as to whether at least some children, possibly a subgroup, with ADHD have more “intrinsic” settling problems at bedtime that are unrelated to either extrinsic factors, co-morbid psychiatric conditions, pharmacologie treatment, or primary or co-morbid sleep disorders.36,37 Some authors have postulated a catecholamine-mediated “hyperarousal” mechanism that prevents or delays settling at bedtime, while others have suggested that at least some of these children may have a melatoninmediated, circadian-based sleep phase delay that results in bedtime resistance when these children are required to fall asleep earlier than their physiologic sleep onset time. An additional possibility is that some intrinsic sleep-wake regulatory dysfunction in these children results in unpredictable or erratic sleep onset latency.

MANAGEMENT

An important treatment goal should be evaluation of any comorbid sleep problems, followed by appropriate diagnostically-driven behavioral and/or pharmacologic intervention.38, 39 Difficulty falling asleep related to psychostimulant use may respond to adjustments in the dosing schedule, because in some children the sleep onset delay is due to a “rebound”effect of the medication wearing off coincident with bedtime, rather than a direct stimulatory effect of the medication itself.

The use of other pharmacologie agents as an alternative to psychostimulants might be considered in children for whom medication- related insomnia is a problem; atomoxctine (Strattera), is a non- stimulant, highly selective inhibitor of presynaptic norepinephrine reuptake which does not appear to have deleterious effects on sleep (40).

It cannot be emphasized enough that all children presenting to health care practitioners with learning, attention, behavioral, or emotional concerns, especially ADHD, should be carefully assessed for underlying or comorbid sleep disorders as part of the routine evaluation. Parents, even the children, may not connect behavioral and learning disorders to sleep problems, and thus may fail to spontaneously volunteer such information. Furthermore, because parents of older children and adolescents may not be aware of any existing sleep difficulties, it is also important to question the patient about sleep.

“…ALL CHILDREN PRESENTING TO HEALTH CARE PRACTITIONERS WITH LEARNING, ATTENTION, BEHAVIORAL, OR EMOTIONAL CONCERNS, ESPECIALLY ADHD, SHOULD BE CAREFULLY ASSESSED FOR UNDERLYING OR COMORBID SLEEP DISORDERS AS PART OF THE ROUTINE EVALUATION.”

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KRISTIN BARTHOLOMEW AND JUDITH OWENS MD, MPH

Kristin Bartholomew, who contributed to this article while an undergraduate at Brown University, is a Project Associate in clinical research at PharmaNet, a contract research organization.

Judith Owens MD, MPH. Affiliations previously cited.

CORRESPONDENCE:

Kristin Bartholomew

1955 Tulpe Way

Riegelsville, PA 18077

phone: (215) 896-6161

e-mail: bartholomewk@gmail.com

Copyright Rhode Island Medical Society Mar 2006