Sleep disorders in patients with ADHD: impact and management challenges

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is one of the most commonly diagnosed disorders in childhood and adulthood. It affects approximately 3%–5% of youth¹ and 2.9% of adults.² It endures throughout adolescence and adulthood. A diagnosis of ADHD is dependent on developmentally inappropriate symptoms of inattention, hyperactivity, and/or impulsivity, with onset before the age of 12 years and impaired functioning in two or more settings. If untreated, individuals with ADHD struggle with impairments across many crucial domains of functioning, including academic, occupational, and social realms.³

In clinical practice, sleep problems are reported in an estimated 25%–50% of individuals who have ADHD,^4–6 and adults who do not get the recommended amount of sleep are more likely to report ADHD symptoms.⁷ Sleep disturbances in such individuals have been associated with comorbid primary sleep issues and/or alterations associated with the medications used to treat ADHD.⁸ In an affected individual, sleep disturbances that result in sleep restriction or sleep fragmentation can lead to excessive daytime fatigue and interfere with mood, attention, behavior, and physical health, all of which are critical for school/work performance and a good quality of life. However, although sleep problems are very common in individuals with ADHD, comorbid sleep disorders are often overlooked and left untreated in ADHD populations.

Researchers have examined the associations between ADHD and sleep-disordered breathing (SDB), restless leg syndrome (RLS), circadian rhythm sleep disorders (CRSDs), insomnia, and narcolepsy.^9–11 SDB is characterized by abnormal patterns of respiration and/or ventilation during sleep,¹² while obstructive sleep apnea (OSA) is characterized by partial or complete upper airway obstruction, leading to disrupted sleep.^13,14 A history of snoring or possible OSA during childhood is associated with a twofold difference in the odds of ADHD diagnosis or symptoms,^15,16 and elevated incidence of SDB is found among individuals with ADHD.^17–21 SDB affects psychological outcomes through various mechanisms, including the deleterious effects of hypoxic insults and the resulting stress/inflammation in the brain and/or repeated arousal-based sleep disruptions.²² These mechanisms can alter the neurochemical substrates of the prefrontal cortex²³ leading to neurobehavioral deficits underlying ADHD symptoms.

RLS is a common sensorimotor disorder characterized by an irresistible urge to move the legs, often accompanied by uncomfortable sensations in the legs or (less frequently) other body parts. These sensations are worse at rest, relieved by movement, and most bothersome in the evening or night. Patients frequently experience insomnia from leg discomfort and the need to move around. Dopaminergic abnormalities and iron deficiency are presumed to underlie this comorbidity.^24–31 Although the prevalence of RLS in the pediatric population is unknown, approximately 10% of adults in the USA have the disorder. The evidence suggests that up to 44% of individuals with ADHD have RLS or RLS-like symptoms and up to 26% of individuals who have RLS have ADHD or ADHD-like symptoms.^{28,30,32–35} The underlying pathophysiology linking RLS and ADHD may lie in the deficit of dopamine in the nigrostriatal brain region, which has been associated with both disorders.³⁶ In addition, iron deficiency has also been linked to ADHD and RLS,³⁷ since iron is a cofactor for tyrosine hydroxylase, the rate-limiting enzyme responsible for dopamine synthesis, which also influences the dopamine pathway directly. Sleep disruption itself may lead to symptoms of ADHD, and daytime symptoms of RLS such as restlessness and inattention may mimic ADHD symptoms.³⁸

CRSDs involve a problem in the timing when a person sleeps and is awake. They are caused by alterations of the circadian time-keeping system or its entrainment mechanisms or by a misalignment of the endogenous circadian rhythm and the external environment. Delayed sleep phase syndrome (DSPS) occurs when a person regularly goes to sleep and wakes up >2 hours later than is considered normal. Individuals with ADHD have been found to have changes in these mechanisms, decreases in the volume of the pineal gland, and/or clock gene abnormalities; in particular, a recent study conducted by Baird et al found that the expression of clock genes BMAL1 and PER2 was altered in individuals with ADHD.³⁹ DSPS and late chronotype are frequently comorbid in adults^3,40,41 and adolescents⁴² with ADHD. The pathophysiology linking ADHD and CRSD maybe both behavioral and biological.⁴³ Deficits in impulsivity control may affect the ability of an individual to settle down, leading to bedtime resistance and resulting in delayed sleep onset. In addition, it is proposed that individuals with ADHD may have a stronger circadian evening preference and possible endogenous melatonin increase delay.^43,44

Insomnia is a sleep disorder characterized by difficulty falling or staying asleep, even when a person has the chance to do so.⁴⁵ Prolonged sleep onset, delayed bedtime, and frequent night awakenings are commonly seen in individuals with ADHD. It is more frequent among children (73.3%)⁴⁶ and adults with ADHD (66.8%)⁴⁷ than in the general population (children: 20%–30%;⁴⁸ adults: 6%–50%^49,50). Unhealthy sleep practices and a lack of routines, especially at bedtime, have been shown to be more common in individuals with ADHD and to have a significant negative impact on sleep initiation.⁵¹ In addition, these sleep issues could result from increased resistance at bedtime, difficulty in settling down in the evening, or poor sleep hygiene.

Narcolepsy is a chronic neurological disease that manifests as difficulty with maintaining continuous wake and sleep. The clinical presentation varies, but a diagnosis of narcolepsy requires excessive daytime sleepiness (EDS) occurring alone or together with features of rapid eye movement (REM), sleep dissociation (eg, cataplexy, hypnagogic/hypnopompic hallucinations, sleep paralysis), and disrupted nighttime sleep. There are two major types of narcolepsy: type 1 narcolepsy diagnosis is based on the individual either having low levels of hypocretin or reporting cataplexy and having EDS; type 2 narcolepsy diagnosis involves EDS in the absence of cataplexy and with normal hypocretin levels.⁴⁵ Retrospectively, adults with narcolepsy were found to have a twofold greater likelihood of having a childhood diagnosis of ADHD compared with controls.⁵² In addition, evidence suggests that children with ADHD experience hypoarousal and that their hyperactive/impulsive symptoms may be compensatory behaviors for fatigue.⁵³ The link between ADHD and narcolepsy is poorly understood,¹¹ but it is hypothesized that EDS in individuals with narcolepsy could result in inattention, poor executive function, and impulse control problems that mimic ADHD and respond well to stimulant medication.^54–56 Ultimately, the overlap of symptoms of ADHD and narcolepsy may lead to diagnostic confusion or misdiagnosis of the disorders.⁵⁴ Another hypothesis is that the link may lie in a shared brain pathophysiology.⁵⁷ In ADHD, a suspected dysregulation of dopamine and noradrenaline is an accepted hypothesis,⁵⁸ and REM sleep, in turn, is affected by noradrenergic and cholinergic neurons.⁵⁹ Dysregulation of noradrenaline could lead to changes in REM sleep similar to that seen in patients with narcolepsy.⁵⁷ In addition, medication geared at treating ADHD targets the abovementioned neurotransmitters,⁶⁰ and there is an overlap with medication used to treat narcolepsy.^61,62 There may also be a possible genetic link between narcolepsy and ADHD. Individuals with ADHD and hypersomnia can have shorter REM latencies and fulfill the criteria for type 2 narcolepsy.⁵⁷ In addition, these individuals tend to have an absence of the DQB1*06:02 allele that is usually found in individuals with type 1 narcolepsy and some individuals with type 2 narcolepsy without ADHD, alluding to the possibility that individuals with ADHD and hypersomnia could be part of a subtype of type 2 narcolepsy.⁵⁷

Previous reviews have described research findings pertaining to sleep and the mechanisms that may underlie the comorbidity between the abovedescribed primary sleep disorders and ADHD.⁶³ However, the existing reviews have neglected to examine the potential impacts of these disorders on the daytime functioning of individuals who present with ADHD and sleep issues.^64–66 This is a problem because in order to provide optimal care, clinicians need to be aware of sleep problems among patients with ADHD and their potential impacts on the very symptoms they are attempting to treat and manage. An investigation of how sleep disturbances impact ADHD symptoms will help clarify the outcomes and management challenges associated with treating individuals with ADHD and comorbid primary sleep disorders. Hence, the goal of the present review is to describe empirical findings pertaining to sleep abnormalities and cognitive, behavioral, emotional, or physical outcomes associated with sleep issues in individuals with ADHD and comorbid primary sleep disorders.

Methods

We employed a narrative review methodology to identify and synthesize empirical studies that have examined the sleep patterns of individuals with ADHD and each of the primary sleep disorders known to be comorbid with ADHD, namely SDB, RLS, CRSD, insomnia, and narcolepsy. Three electronic databases were searched in July 2018 (Embase, MEDLINE, and PsycINFO) for studies published in the prior 5 years (between January 1, 2013 and July 1, 2018). Additional records were identified by searching the references of the selected original research papers and review articles.

Separate parallel searches were conducted for each primary sleep disorder using the following key words: ADHD and narcolepsy; ADHD and CRSD, dim light melatonin onset, light therapy, or melatonin; ADHD and restless leg syndrome, RLS, periodic and extremities, periodic limb movement, iron, ferritin, ferritins, levodopa, or L-DOPA; ADHD and sleep apnea or sleep-disordered breathing; and ADHD and insomnia. The inclusion criteria were: 1) peer-reviewed original research of subjects with a sleep disorder or ADHD, in which variables related to both ADHD and sleep were measured; and 2) studies that were written in the English language and used quantitative methods. All the included published empirical studies are listed in the summary table (see Table 1). In total, the literature search yielded 39 relevant papers, including thirteen, seven, eight, seven, and six for ADHD and SDB, RLS, CRSDs, insomnia, and narcolepsy, respectively.

Table 1 Summary of studies reviewed Abbreviations: 6-OH MS, 6-hydroxymelatoninsulfate; ABAS-II, Adaptive Behavior Assessment System, second edition; ADHD, attention-deficit/hyperactivity disorder; ADHD-C, ADHD combined subtype; ADHD-DC, ADHD Diagnostic Checklist; ADHD-I, ADHD inattentive subtype; ADHD-RS, ADHD Rating Scale; AHI, Apnea-Hypoapnea Index; ANT, Attention Network Task; ASD, autism spectrum disorder; ASRS, ADHD Self-Report Scale; AT, adenotonsillectomy; BASC-2: Behavior Assessment for Children, second children; BDI, Beck Depression Inventory; BIS, behavioral inhibition system; BMI, body mass index; CAARS, Conners’ Adult ADHD Rating; CAARS-S:L, Conners’ Adult ADHD Rating Scales – Self-report, Long version; CBCL, Child Behavior Checklist; CBT, core body temperature; CCTQ, Children’s Chronotype Questionnaire; CDI, Children’s Depression Inventory; CGI-P, Conner’s Global Index, parent version; CHSQ, Children’s Sleep Habits Questionnaire; CIDI, Composite International Diagnostic Interview; CPRS, Conner’s Parent Rating Scale; CPRS-R, Conner’s Parent Rating Scale, revised; CPT, Continuous Performance Test; CRSD, circadian rhythm sleep disorder; CSF, cerebrospinal fluid; CSHQ, Children Sleep Habits Questionnaire; CSHS, Children Sleep Hygiene Scale; CTRS, Conner’s Teacher Rating Scale; DAS, Differential Ability Scale; DISC-IV, Diagnostic Interview Schedule for Children; DIVA 2.0, Diagnostic Interview for ADHD in Adults; DLMO, dim light melatonin onset; DSISD, Duke Diagnostic Interview for Sleep Disorders; DSM-IV, Diagnostic and Statistical Manual, fourth edition; DSM-IV-TR, Diagnostic and Statistical Manual, fourth edition, text revision; DSPS, delayed sleep phase syndrome; EDAH, evaluation of deficit of attention and hyperactivity; ESS, Epworth Sleepiness Scale; FBB-HKS, Symptom Checklist for Attention Deficit Hyperactivity Disorders; FSS, Fatigue Severity Scale; GSAQ, Global Sleep Assessment Questionnaire; HADS, Hospital Anxiety and Depression Scale; ICD-9, International Classification of Diseases, ninth revision; ICSD-2, International Classification of Sleep Disorders, second edition; ICSD-3, International Classification of Sleep Disorders, third edition; IED, intra-/extradimensional set shift; IRLSSG, International Restless Leg Syndrome Study Group; IQ, intelligence quotient; ISI: Insomnia Severity Scale; ISI-C, Insomnia Severity Index for Children; IVA-CPT, Integrated Visual and Auditory Continuous Performance Test; JSS, Jenkins Sleep Scale; KINDL, Questionnaire for Measuring Health-related Quality of Life in Children and Adolescents; K-SADS, Kiddie Schedule for Affective Disorders and Schizophrenia; K-SADS-PL, Kiddie Schedule for Affective Disorders and Schizophrenia, present and lifetime version; K-WISC-III, Korean Wechsler Intelligence Scale for Children, third edition; MCTQ, Munich Chronotype Questionnaire; MEQ, Morningness-Eveningness Questionnaire; MFFT-KC, Matching Familiar Figure Test for Korean Children; MOCI, Maudsley Obsessive Compulsive Index; MPH, methylphenidate; MSLT, multiple sleep latency test; MWT-B, multiple choice vocabulary test; NEPSY, A Developmental Neuropsychological Assessment; OCD, obsessive-compulsive disorder; OCIr, Obsessive-Compulsive Index-revised; OSA, obstructive sleep apnea; OSA-18, Obstructive Sleep Apnea-18; OSAHS, obstructive sleep apnea hypopnea syndrome; PDSS, Pediatric Daytime Sleepiness Scale; PedsQL, Pediatric Quality of Life Inventory; PLMD, periodic limb movement disorder; PLMI, periodic limb movement index; PLMS, periodic limb movement syndrome; PSG, polysomnography; PSQI, Pittsburgh Sleep Quality Index; REM, rapid eye movement; RLDI, Restless Leg Diagnosis Index; RLS, Restless Leg Syndrome; RME, rapid maxillary expansion; RWT, Regensburger Wortflussigkeits-Test; SCARED, screen for child anxiety related disorders; SCID-I, Structured Clinical Interview for DSM-IV Axis I Disorders; SDB, sleep-disordered breathing; SDQ, Strengths and Difficulties Questionnaire; SDSC, Sleep Disturbance Scale for Children; SF-36, Short form (36) Health Survey; SHQ, Sleep Health Questionnaire; SMFQ, Moods and Feelings Questionnaire; SNS, Swiss Narcolepsy Scale; SOC, Stockings of Cambridge; SRBD, Sleep Related Breathing Disorders questionnaire; SSS, Stanford Sleepiness Scale; STAI, State-Trait Anxiety Index; TCI, Temperament and Character Inventory; WISC-R, Wechsler Intelligence Scale for Children, revised; WURS-K, Wender-Utah Rating Scale, short form.

Results

In the following sections, findings based on recent empirical data on the sleep characteristics and their associations with daytime functioning and physical health of individuals with ADHD primary sleep disorders are reviewed. These results are organized separately for each of these subgroups in the following way: findings regarding sleep, sleepiness, or circadian characteristics are subdivided according the nature of the tools that were used (objective or subjective measures) and the age groups of the participants. Daytime impairments are divided into cognitive, emotional, and physical outcomes. Detailed information for each study referenced can be found in Table 1.

ADHD and SDB

The present review includes 13 studies (six cross-sectional, two case–control, one retrospective cohort, two prospective cohort, and two open-label) that examined the sleep characteristics of individuals with SDB and ADHD.

Sleep characteristics^67–76

Polysomnography (PSG)

School-age children. N/A; Adolescents. N/A; Adults. No significant differences in apnea–hypopnea index, a measure of apnea and hypopnea events per hour of sleep, in individuals with OSA with and without ADHD.⁷⁴

Subjective measures

School-age children. N/A; Adolescents. N/A; Adults. Increased levels of self-reported loud snoring and breathing pauses during sleep in individuals with ADHD compared with healthy controls.⁷⁷

Daytime impairments

Cognitive impairments

Subjective measures

Pre-school and school-age children. In children with SDB, significantly more symptoms of hyperactivity/inattention but not impulsivity were reported compared with healthy controls.^67,78 Adolescents. N/A; Adults. Individuals with OSA symptoms had high levels of self-reported inattention and hyperactivity when compared with individuals without OSA symptoms.⁷⁹

Objective measures

School-age children. Performance of children who reported frequent snoring (over three times per week) was poorer on tasks measuring attention, executive functions, language, intellectual functioning, and information processing when compared with healthy children who did not snore as frequently⁶⁷ (less than two times per week). In addition, children with diagnosed OSA performed worse on measures of sustained attention compared with typically developing children.⁷² Adolescents. N/A; Adults. N/A.

Emotional impairments

Pre-school and school-age children. Children with OSA and ADHD had lower ratings on quality of life compared with individuals with OSA alone.⁸⁰ Adolescents. N/A; Adults. Individuals with OSA and ADHD had lower ratings on quality of life and higher levels of reported symptoms of depression and anxiety than individuals with OSA alone.⁷⁴

Physical impairments

Pre-school and school-age children. Severity of ADHD symptoms was associated with allergic rhinitis, adenoid hypertrophy, and tonsil hypertrophy in individuals with ADHD and OSA.⁸⁰ Adolescents. N/A; Adults. No difference was found in body mass index (BMI) between individuals with OSA and ADHD and OSA alone.⁷⁴

ADHD and RLS

The present review includes seven studies (four cross-sectional, two case–control, and one randomized control trial) that examined the sleep characteristics associated with RLS and ADHD.

Sleep characteristics^81–85

PSG

School-age children. A higher periodic limb movement disorder index was found for children with ADHD and RLS compared with healthy controls⁸³ and for children with ADHD alone compared with healthy controls.⁸² Individuals with ADHD alone did not differ in periodicity of leg movements compared with healthy controls.⁸² Children with ADHD and RLS showed prolonged sleep latency, increased number of stage shifts, awakenings, and increased percentage of sleep stage 1 compared with healthy controls;⁸³ Adolescents. N/A; Adults. Individuals with ADHD had a higher periodic limb movement disorder index, longer sleep latency, and increased periodicity of leg movements compared with healthy controls.⁸⁵

Actigraphy

School-age children. Multiple night awakenings, sleep hyperkinesias, and periodic limb movements were found in children with ADHD.⁶² Adolescents. N/A; Adults. N/A.

Subjective measures

School-age children. Children with ADHD reported more restless legs symptoms when compared with healthy controls.⁸⁴ Adolescents. N/A; Adults. Higher levels of ADHD symptoms were reported by individuals with RLS, but the association between RLS and ADHD was no longer significant when accounting for sleep disturbances.⁸⁶

Physiological correlates

School-age children. No differences were found in serum transferrin and iron levels between children with ADHD and healthy controls.⁸⁴ Regarding ferritin levels two studies^84,87 reported no difference in ferritin levels between individuals with ADHD and healthy controls, whereas another study⁸¹ reported overall low ferritin levels in individuals with ADHD. Adolescents. N/A; Adults. No differences were found in serum ferritin and iron levels between individuals with RLS with or without ADHD. In addition, iron and ferritin levels did not correlate with RLS severity scores.⁸⁷

Cognitive impairments

Subjective measures

School-age children. N/A; Adolescents. N/A; Adults. N/A.

Objective measures

School-age children. Verbal IQ on the Wechsler Intelligence Scale was positively correlated with stages 3 and 4 of sleep and limb movement index with arousals. It was negatively correlated with stage 2 of sleep.⁸² On the Matching Familiar Figure Test for Korean Children (MFFT-KC), an instrument designed to measure reflection-impulsivity, more response errors were associated with longer sleep time and limb movement index with arousals and longer reaction time was associated with shorter duration of stage 2 of sleep.⁸² Adolescents. N/A; Adults N/A.

Emotional impairments

No studies were conducted to assess emotional outcomes in individuals with RLS and ADHD.

Physical impairments

School-age children. N/A; Adolescents. N/A; Adults. A study found that RLS participants were more likely to be obese (BMI >30) than participants without RLS (28.5% of the RLS group compared with 10.1% of healthy controls).⁸⁶

ADHD and CRSD

The present review includes eight studies (two cross-sectional, four case–control studies, and two open-label) that examined the sleep characteristics associated with CRSD and ADHD.

Sleep characteristics

PSG

No PSG study was conducted in individuals with ADHD and CRSD.

Actigraphy

School-age children. N/A; Adolescents. N/A; Adults. An actigraphic study revealed that sleep start time was 2:20 hours later, and sleep duration 1:08 hours shorter, sleep midpoint was delayed by 1 hour and 52 minutes, and sleep efficiency was higher in adolescents with ADHD and DSPS compared with healthy controls.⁶⁹

Objective circadian measures

School-age children and adolescents. Children and adolescents with ADHD (6–16 years) had higher urinary levels of 6-hydoxymelatoninsulfate (a urine melatonin metabolite) at daytime, nighttime, and over 24 hours compared with healthy controls.^88,89 Treatment with methylphenidate reduced urinary melatonin excretion and lowered morning melatonin in children with ADHD.⁹⁰ Adults. Dim light melatonin onset occurred 1 hour and 23 minutes later in individuals with ADHD and DSPS compared with healthy controls.⁹¹

Subjective sleep and circadian measures

School-age children. Inconsistent findings were found in children with ADHD manifesting greater eveningness in one of the two studies conducted to assess circadian tendencies in this population compared with healthy controls.^92,93 Evening chronotype was associated with more resistance to sleep, respiratory problems, and daytime sleepiness.⁹² Adolescents. Individuals with higher ADHD symptoms (>90th percentile on the ADHD Self-Report Scale [ASRS]) reported later bed and wake up times, shorter sleep duration, and lower sleep efficiency compared with individuals with low ADHD scores (<90th percentile on ASRS).⁹⁴ Adults. Greater eveningness was found in individuals with ADHD compared with healthy controls. Eveningness was related to higher severity of the ADHD symptoms.^40,95

Daytime impairments

Cognitive impairments

Subjective measures

School-age children. N/A; Adolescents. N/A; Adults. Delayed sleep timing and daytime sleepiness were associated with higher levels of reported inattention and hyperactivity in participants with ADHD and DSPD compared with healthy controls.⁹⁶ Evening chronotype was associated with higher levels of ADHD symptoms.^40,89,95

Objective measures

No studies using objective cognitive measures were conducted in individuals with CRSD and ADHD.

Emotional impairments

No studies were conducted to assess emotional outcomes in individuals with CRSD and ADHD.

Physical impairments

School-age children. Psychosomatic symptoms (stomach aches, aches and pains, complains of headaches, seems tired) on the Conner’s Parent Rating Scale were correlated to eveningness in the ADHD group.⁹² Adolescents. N/A; Adults. N/A.

ADHD and insomnia

The present review includes nine studies (three cross-sectional, five case–control, and one randomized control trial) that examined the sleep characteristics associated with insomnia and ADHD.

Sleep characteristics

PSG

No PSG study was conducted in individuals with ADHD and insomnia.

Actigraphy

School-age children. Actigraphic studies^97,98 revealed longer sleep onset latency, lower sleep efficiency, and lower total sleep time in children with ADHD alone compared with healthy controls. However, these measures were worse for children with ADHD and a comorbid psychiatric disorder (eg, anxious, depressed, oppositional symptoms) when compared with individuals with ADHD alone and healthy controls.⁹⁷ Adolescents. N/A; Adults. N/A.

Subjective sleep measures

School-age children. Parental reports described longer sleep onset delay,^97,99 shorter sleep duration, and more restless sleep in children with ADHD compared with healthy controls.⁹⁷ Children with ADHD hyperactive/impulsive subtype scored higher on measures of insomnia compared with individuals with an inattentive type,¹⁰⁰ and no differences in insomnia scores between children with ADHD and healthy controls were found in another study.⁹⁹ Adolescents. Sleep duration and time in bed were shorter for individuals scoring high (over 90th percentile) in self-reported ADHD symptoms compared with those with low scores (<90th percentile).⁹⁴ The association was stronger for individuals with ADHD-inattentive subtype compared with ADHD hyperactive or combined subtypes.⁷⁴ Adults. Subjective complaints of poor sleep quality, EDS sleep onset insomnia, and interrupted sleep as per the cutoff scores on the Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index were prevalent in samples of individuals with ADHD compared with controls.⁴⁷ Sleep quality was poorer in individuals with ADHD and an inattentive subtype compared with individuals with a combined subtype.¹⁰¹ Individuals with ADHD reported prolonged sleep latencies (>30 minutes) on the Pittsburgh Sleep Quality Index compared with controls.¹⁰² Adult women with ADHD reported higher prevalence of insomnia (43.9% vs 12.2%) compared with women without ADHD.¹⁰³

Daytime impairments

Cognitive impairments

Subjective measures

No studies using subjective cognitive measures were conducted in individuals with insomnia and ADHD.

Objective measures

School-age children. N/A. Adolescents. Individuals with ADHD and shorter duration of nighttime sleep had more omission errors compared with healthy controls on a measure of executive function.⁹⁹ Adults. N/A.

Emotional impairments

School-age children. Quality of life scores were reduced in children with insomnia and ADHD compared with healthy controls.¹⁰⁰ Adolescents. N/A. Adults. N/A.

Physical impairments

School-age children. N/A. Adolescents. N/A; Adults. N/A.

ADHD and narcolepsy

The present review includes six studies (four cross-sectional and two case–control) that examined the sleep characteristics associated with narcolepsy and ADHD.

Sleep and sleepiness

PSG

School-age children. PSG studies showed longer total sleep times, shorter sleep latency, and shorter onset of REM periods in children with ADHD and narcolepsy compared with healthy controls.^81,104 Adolescents and adults. Shorter stage 1 and longer stage 3 of sleep were found in adolescents and adults with narcolepsy and ADHD compared with individuals with narcolepsy without ADHD.⁵⁷

Actigraphy

School-age children. Participants with ADHD and sleep problems, including three individuals with narcolepsy, displayed sleep efficiency of <90%.⁸¹ Adolescents. N/A; Adults. N/A.

Multiple Sleep Latency Test (a diagnostic tool used to objectively measure sleepiness and early-onset REM sleep)¹⁰⁵

School-age children. N/A; Adolescents and Adults. Individuals with ADHD and comorbid narcolepsy type 2 had shorter REM sleep latencies compared with individuals with narcolepsy type 2 alone.⁵⁷

Subjective measures

Four studies used subjective measures to describe sleep outcomes (Children Sleep Habits Questionnaire, Pediatric Daytime Sleepiness Scale, Epworth Sleepiness Scale, Stanford Sleepiness Scale). For children, parents were the main respondents to the questionnaires. Clinicians also provided subjective information after interviewing the children.

School-age children. Higher levels of ADHD symptoms were associated with higher levels of reported sleepiness and fatigue.^81,106 Adolescents. N/A; Adults. Individuals with attention deficits and narcolepsy reported more sleepiness compared with healthy controls.¹⁰⁷

Cognitive impairments

Subjective measures

School-age children. Higher levels of inattention was found in children with narcolepsy compared with healthy controls.^104,106 Poor sleep and fatigue in participants diagnosed with narcolepsy were associated with increased levels of inattention;¹⁰⁶ Adolescents. N/A; Adults. Higher levels of inattention symptoms and higher hyperactivity scores were found in patients with narcolepsy compared with healthy controls.¹⁰⁸

Objective measures

School-age children. N/A; Adolescents. N/A; Adults. When comparing individuals with ADHD and narcolepsy to healthy controls, no significant differences were found in attention span and verbal working memory.¹⁰⁷ However, reduced verbal fluency,¹⁰⁷ greater difficulty in performing under time pressure, poorer performance on measures of executive functions (Go/no go test,¹⁰⁷ Attention Network Test¹⁰⁸) were observed in adults with narcolepsy and ADHD compared with healthy controls.

Emotional impairments

School-age children. Children with narcolepsy and comorbid ADHD symptoms had more depressive symptoms and decreased quality of life compared with healthy controls.¹⁰⁶ Adolescents. N/A; Adults. Higher depression and ADHD scores were found in individuals with narcolepsy type 1 compared with controls.^107,108

Physical impairments

School-age children. One study found a higher proportion of overweight or obesity in children with narcolepsy compared with healthy controls.¹⁰⁶ Although the narcolepsy group did have a higher proportion of ADHD individuals and individuals with overweight and obesity, the association between ADHD and obesity was not examined. Adolescents. N/A; Adults. Higher BMI was found in individuals with ADHD and narcolepsy type 1 compared with participants with narcolepsy type 2 and healthy controls.¹⁰⁸

Discussion

This review aimed to describe empirical studies pertaining to sleep abnormalities and outcomes in individuals with ADHD and comorbid primary sleep disorders in order to identify and address management challenges associated with treating these individuals.

Consistent with many previous studies, reviews, and meta-analyses, most of the PSG studies have failed in establishing consistent sleep differences in sleep architecture between individuals with sleep disorders with and without ADHD. However, a few differences have emerged. Children with ADHD and RLS were found to have an increased percentage of sleep stage 1 compared with healthy controls,⁸³ whereas for individuals with ADHD and narcolepsy, a shorter stage 1⁵⁷ and shorter REM latency^57,104 were found across all age groups compared with individuals without ADHD.

A few studies have also shown that children with ADHD and RLS and adults with ADHD alone have longer sleep latencies compared with healthy controls,^83,85 and children with ADHD and narcolepsy have shorter sleep latencies compared with healthy controls.^81,104 In addition, children with ADHD and narcolepsy were found to have lower sleep efficiency compared with healthy controls.⁸¹ In an actigraphic study, only children with ADHD were found to have more night awakenings and increased level of hyperkinesias.⁸¹

Subjective sleep reports both from parents of children with ADHD and adults with ADHD have consistently reported high prevalence of sleep problems.^{40,47,77,81,86,92,94,95,97,99,101,106,107} Higher level of reported sleepiness was found for individuals with ADHD and OSA⁷⁷ and individuals with ADHD symptoms and narcolepsy^81,106,107 compared with those without ADHD and healthy controls, respectively. Individuals with ADHD reported increased daytime sleepiness across studies^{40,47,81,92,106,107} as well as shorter sleep duration^82,91,94,97 compared with healthy controls. Finally, having an evening circadian type was more prevalent for individuals with ADHD^40,89,92,95 compared with healthy controls.

Only a few empirical studies have examined daytime impairments in individuals with ADHD and comorbid primary sleep disorders. Regarding cognitive impairments, studies revealed higher levels of reported symptoms of hyperactivity and inattention in children with SDB^68,78 and narcolepsy^104,106 and adults with OSA,⁷⁹ DSPD,⁹⁶ and narcolepsy¹⁰⁸ compared with healthy controls. Studies using objective cognitive measures revealed variable impairments across disorders and age groups. Children with OSA symptoms had impairments in attention, executive functions, language, intellectual functioning, and information processing compared with those without OSA symptoms.^67,72 The impairment in executive functions and verbal fluency was also seen in adults with ADHD and narcolepsy¹⁰⁸ compared with healthy controls.¹⁰⁷ There were no empirical studies looking at cognitive impairments in individuals with ADHD and insomnia or RLS across the different age groups.

There is a dearth of empirical studies examining emotional impairments related to disrupted sleep in individuals with ADHD and primary sleep disorders. Lower perceived quality of life was reported in children with ADHD and SDB,⁸⁰ insomnia¹⁰⁰ and narcolepsy,¹⁰⁶ and adults with ADHD and SDB⁷⁴ compared with healthy controls. Higher level of depression and anxiety symptoms were reported in adults with ADHD and OSA⁷⁴ and narcolepsy¹⁰⁷ alone compared with healthy controls. A complete lack of empirical data is noted for the assessment of emotional impairments in individuals with ADHD and RLS, CRDS, or adults with insomnia. Knowing that sleep disturbances significantly intensify emotional reactivity and negative mood and impair emotional regulation, this lack of information represents a significant gap in knowledge as well as a significant barrier to effective clinical management.

Scarce empirical data exist for physical impairments or comorbid conditions in individuals with ADHD and primary sleep disorders. For children with ADHD and SDB, an increase in medical comorbidities including allergic rhinitis, tonsillar, and adenoid hypertrophy was found compared with healthy controls;⁸⁰ however, this finding cannot be generalized across the age groups due to lack of empirical data. Furthermore, these medical comorbidities are unlikely to be present in adults since these structures (adenoids/tonsils) atrophy following puberty.¹⁰⁹ In addition to medical comorbidities, the presence of comorbid primary sleep disorders was associated with increased BMI. Adults with RLS⁸⁶ and narcolepsy¹⁰⁸ are both found to have higher BMI compared with individuals without RLS and healthy controls, respectively, and children with narcolepsy have increased overweight and obesity compared with healthy controls.¹⁰⁶ There are no empirical data regarding physical impairments or medical comorbidities for individuals with ADHD and insomnia across ages as well as children with ADHD and RLS and adults with ADHD and CRDS.

Clinical implications

The high prevalence of subjective complaints regarding sleep disturbances in individuals with ADHD across all age groups, and the prevalence of daytime symptoms of inattention and hyperactivity in individuals with primary sleep disorders, suggests that a baseline sleep evaluation during the initial assessment of ADHD as well as regular systematic screening for sleep problems is necessary component of ongoing ADHD management. This is of particular importance given that the presence of such sleep problems will likely decrease the efficacy of an intervention aimed solely at improving ADHD symptoms. As a first step, it is essential to delineate the nature of the reported sleep problems in order to eventually be able to properly treat them. It is also a possibility that there may be concomitant sleep disorders that are manifested simultaneously; therefore, having a thorough and systematic approach that includes objective sleep measures such as PSG, actigraphy, Multiple Sleep Latency Test along with obtaining detailed clinical history of the sleep, and ADHD challenges will help in establishing a clear diagnosis.

In order to undergo such tests, the treating physician will need to have access to referral to a facility that is capable of performing them. In turn, a sleep specialist will need access to a physician able to diagnose ADHD as well as psychological comorbidities in order to have a clear baseline. Collaboration between health professionals will be essential in treating these individuals and will be an integral part of the initial assessment.

Furthermore, a particular challenge will surface when assessing an adolescent population. Developmentally, during adolescence, sleep needs will naturally change. A key differentiation between normal sleep changes (eg, regular delayed sleep) and a sleep disorder (eg, DSPS) will need to be properly established.

Following a delineation of each problem, establishing a clear timeline of symptoms will be helpful to evaluate whether the symptoms of ADHD or the sleep disorder have a temporal relationship or whether they are comorbid. Moreover, it will be essential to establish whether the sleep problem is a cause or a consequence of the psychiatric comorbidity or vice versa and whether this stands true for the individual across their life span. Knowing that there is a significant prevalence of sleep disorders in ADHD and vice versa may lead to misattributions of symptoms of inattention and hyperactivity, for example, to ADHD and not a consequence of a sleep disorder. This issue will also impact the psychosocial treatment strategy as well as the pharmacologic treatment by a sleep specialist or a psychiatrist.

In addition to establishing a clear diagnosis, determining its impact or associations with daytime neuropsychological, emotional, or physical impairments would allow to map the sequence and magnitude of the required interventions. For example, if sleep disruption contributes to daytime inattention or executive dysfunction, treating it might be an ideal first step prior to or in addition to prescribing stimulant medications to address these challenges. Similarly, if sleep disturbances play a role in emotional dysregulation or low mood, treating sleep disturbance should be an important step in addressing the sleep and the comorbid disorders. In these cases, having a multidisciplinary approach will allow for simultaneous evaluation and treatment and collaboration with the goal of improving both the primary problem and the associated symptoms (eg, daytime impairments).

In terms of treatment, the first step following assessment and diagnosis will consist of psychoeducation. Both the individual affected and the social entourage of these individuals (parents, spouses, etc) will need to have proper psychoeducation on ADHD symptoms as well as the particular sleep disorder in addition to its course, prognosis, treatment, and possible functional implications. Furthermore, education on normal sleep patterns and sleep hygiene will allow for nonpharmacological improvement of sleep.

Using medication to treat sleep disorders is widespread. Medication selection, particularly if treatment for ADHD is warranted, can be targeted to improve associated problems such as daytime impairments and should be integrated with behavioral strategies. For children with ADHD and SDB, surgical removal of the adenoids or tonsils is a first-line treatment,¹¹⁰ whereas for adults with ADHD and OSA, the use of positive airway pressure devices, oral appliances, or surgery are recommended treatment options.¹¹¹ For individuals with ADHD and RLS, behavioral interventions could include modifying the sleep environment and treatment with iron supplementation¹¹² (eg, ferrous sulfate) or gabapentin¹¹³ could be considered, in particular for a younger population. Treatment with dopaminergic agents such as pramipexole, ropinirole, L-DOPA, and a relatively new medication, rotigotine, in an adult population could also be an option.¹¹⁴ For individuals with ADHD and DSPS, treatment with light therapy¹¹⁵ and chronotherapy¹¹⁶ can be explored as well as using timed melatonin treatment.¹¹⁷ Treatment for individuals with ADHD and insomnia will vary according to age group, and in addition, a clear distinction between insomnia and DSPS will have to be made given that treatment for DSPS will be different than that for insomnia. For children with ADHD and insomnia, behavioral treatments such as positive reinforcement, scheduled awakenings, unmodified extinction, and faded bedtime could be starting options.¹¹⁸ For adolescents with ADHD and insomnia, cognitive behavioral therapy for insomnia (CBT-I) can be an effective treatment.¹¹⁹ In adults with insomnia, CBT-I, stimulus control therapy, relaxation training, sleep restriction, multicomponent therapy, paradoxical intention, and biofeedback can be used alone or in conjunction with sleep medication,¹¹⁸ although treatment with pharmacotherapy for insomnia has weak evidence.¹²⁰ For individuals with ADHD and narcolepsy, treatment with modafinil, sodium oxybate, or psychostimulants is indicated and it can be supplemented with education on sleep hygiene.¹²¹ Treating with psychostimulants would allow for the added benefit of treating both underlying disorders and not restrict the treating physician for the treatment of symptoms only.

Limitations and future directions

The limitations of available empirical evidence give rise to several challenges. A key challenge is integrating information from studies that differ in the participants included in the clinical and/or the control groups. Although all the studies included in the present work examined sleep and/or daytime impairments of individuals with ADHD and primary sleep disorders, some included only individuals with diagnosed ADHD in the study group, whereas others included individuals with sleep disorders only or individuals with a diagnosis of both ADHD and a primary sleep disorder. Studies also varied in the characteristics of the control group, with some comparing the study group with a different clinical group and others comparing the study group with healthy controls. In addition, some studies included individuals with psychological comorbidities or individuals undergoing pharmacotherapeutic treatment, making the sample more heterogeneous. The interstudy differences in the study and control groups limited the ability to generalize findings across studies in some cases that precluded direct comparison of studies. A second challenge in the present work was that, for children, many of studies used parent reports or clinician evaluations to obtain information on subjective sleep measures and daytime impairments. Due to the use of subjective and retrospective reports from parents, the results must be interpreted with caution. In adolescents, few studies assessed objective and subjective sleep impairments or daytime impairments, and overall there is a dearth of literature for this population. The present work was made even more challenging by the small number of longitudinal and experimental studies that have been published in this area. The lack of such studies limited the ability to establish a better understanding of the nature and the direction of the associations between primary sleep disorders and ADHD. An alarming shortage of empirical evidence on daytime impairments caused by sleep disturbances in individuals with ADHD was noted across all domains and all age groups. Furthermore, in the few studies to date that have examined daytime impairments, the cognitive, emotional, or physical outcomes were poorly defined and were inconsistent between studies. This significantly limited the ability of the review to ascertain the nature and magnitude of the impairments caused by the presence of a primary sleep disorder in individuals with ADHD, above and beyond or in combination with the impairments they present with as a result of their ADHD.

Future research should focus on the systematic and thorough evaluation of daytime impairments associated with the combined impacts of ADHD and sleep disturbances on individuals with both conditions. Such research should clearly define outcomes that take into consideration the manners in which cognitive, emotional, and physical impairment may manifest at different ages, and should apply those definitions systematically across disorders. Ideally, these studies would compare individuals with ADHD and each of the primary sleep disorders known to be associated with ADHD to individuals with ADHD alone and to healthy controls. Results of these studies are needed to better appreciate patient needs and to inform clinical management.

Additional studies should also be conducted to capture the clinical characteristics and daytime impairments of all age groups, in particular adolescents and elderly patients (for whom there is no available empirical evidence). In addition, longitudinal studies are needed that evaluate changes in sleep, ADHD, and potential impairment over time, and that track the impacts of interventions on the sleep and daytime functioning of individuals with ADHD and comorbid sleep disorders.

Disclosure

The authors report no conflicts of interest in this work.

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