Points of Interest
• Sleep disorders affect approximately 20 to 30% of the general pediatric population. In the ASD population the prevalence is much higher and is estimated at between 44 and 86%. The most commonly reported problem is insomnia, which can include inability to initiate sleep and difficulty maintaining sleep.
• Children with ASD are at risk for other medical problems and frequently receive psychotropic medications, both of which can impact sleep. The etiology of sleep problems in children with ASD is likely multifactorial, including genetic and environmental factors as well as medical and behavioral issues.
• The most common parasomnia reported in children with ASD is bruxism (18%). Other reported parasomnias include sleepwalking and night wakings associated with either inconsolable screaming or a frightening dream.
• Sleep problems experienced by children are frequently associated with disturbances in neurocognition and behavior. In children, common consequences of poor sleep include difficulty with mood regulation and impulse control, hyperactivity or daytime sleepiness, poor concentration and impaired memory. The impact of impaired sleep on daytime functioning may be even more severe in children with poor self-regulation, a deficit common in children with ASD. Poor sleep may exacerbate existing behavioral problems.
• Parent report measures are a quick and easy way for clinicians to screen for sleep problems. The two most commonly used measures in the pediatric population are the Children’s Sleep Habits Questionnaire (CSHQ) and the BEARS. Objective measures of disturbed sleep include at home use of a physical activity monitor, or actigraph, and clinical polysomnography.
• Sleep problems should be treated first with behavioral therapy. If problems persist, consideration can be give to use of pharmacologic sleep aids.
Sleep problems in children with autism spectrum disorders (ASD) are a significant issue and warrant a place in routine clinical evaluation. Evidence consistently indicates that children with an autism spectrum disorder are more likely to have a sleep disorder than typically developing children. A wide range of sleep disorders are reported in this population, with the most common being insomnia, including difficulty falling asleep and staying asleep. Furthermore, sleep disorders negatively impact the daytime functioning of both the child and family members, as well as exacerbate coexisting medical, psychiatric, psychosocial, and developmental problems. Progress has been made in understanding pediatric sleep disorders that will contribute to better care for children with ASD and sleep problems. Reliable and valid methods for identifying and characterizing sleep problems in children exist, including short screening questionnaires that can be easily administered at any point of contact. When sleep problems are identified, effective treatments are available. In this chapter we will consider an overview for the clinician of the clinical presentations of sleep disorders in children with autism spectrum disorders, as well as discuss the evaluation and treatment of these disorders.
Prevalence and Correlates
Sleep disorders affect approximately 20 to 30% of the general pediatric population (Owens, Spirito, et al., 2000b; Sadeh, Raviv, et al., 2000). In the ASD population the prevalence is much higher and is estimated at between 44 and 86% (Richdale & Prior 1995; Wiggs & Stores, 1996; Patzold, Richdale, et al., 1998; Allik, Larsson, et al., 2006). This high prevalence cannot be explained by level of cognitive functioning alone. A study of parent-reported sleep problems in children with pervasive developmental disorder (PDD) and normal intelligence found that 78% of parents reported sleep problems in these children, compared to 26% of parents of an age-and gender-matched group of typically developing children (Couturier, Speechley, et al., 2005). Further, a large study comparing children with ASD (n = 303; ADI and ADOS confirmed) to children with developmental delays, but no ASD (n = 63) and typically developing children (n = 163) found that children with ASD had a higher prevalence of parent-reported sleep problems than either of the two comparison groups. Fifty-three percent of children in the ASD group had at least one frequent sleep problem, compared to 46% and 32%, respectively, of the developmentally delayed and typically developing groups (Schreck, Mulick, et al., 2004). It appears ASD may be a risk factor for sleep problems independent of level of cognitive functioning.
The most commonly reported problems include inability to initiate sleep and difficulty maintaining sleep (Table 26-1). Parents have reported that their children with ASD have trouble going to bed on time, wake frequently during the night, and wake early (Richdale & Prior, 1995; Johnson et al., 2008; Krakowiak et al., 2008; Richdale et al., 2009). Also reported are irregular sleep-wake patterns and poor sleep routines (Hoshino, Watanabe, et al., 1984; Clements, Wing, et al., 1986; Quine 1991; Patzold, Richdale, et al., 1998; Owens, Spirito, et al., 2000b; Schreck & Mulick, 2000; Honomichl, Goodlin-Jones, et al., 2002; Meltzer, 2008). During objective evaluations using actigraphy, children with ASD exhibited less total sleep time in 24 hours than children with developmental delay without ASD and typically developing children (Goodlin-Jones et al., 2008). The children with developmental delay exhibited more and longer awakenings after sleep onset than the ASD or typically developing children. The presentation of sleep problems in children with ASD is discussed in more detail later in this chapter.
Table 26–1. Commonly reported sleep problems in autism spectrum disorders
40–80%; General Pediatric Population 10–30%
Circadian Rhythm Disorder
4–35%; General Pediatric Population 1%
Delayed Sleep Phase
Irregular Sleep Schedule
Not known; in a small case
report study RBD occurred in 45%
NREM Parasomnias (Sleep walking; Night Terrors)
REM Sleep Behavior Disorder
Note: Sleep Disordered Breathing (Obstructive sleep apnea) and Sleep Related Movement Disorders not listed; prevalence not known, but may be similar to the general pediatric population.
As with other aspects of the ASD phenotype, sleep problems are a complex and variable phenomenon in this group. The high number of children who experience at least one sleep problem warrants screening for sleep problems in all children with ASD. There are some subgroups that are at increased risk. A 2008 study using the Children’s Sleep Habits Questionnaire found that children with developmental regression were significantly more likely to experience sleep problems than children who did not have a regressive-onset of autism (Giannotti, Cortesi, et al., 2008). Similarly to typically developing children, sleep problems are more likely to be reported in children younger than 5 years and are more severe in children with intellectual disability (Richdale & Prior, 1995).
Typical Sleep Architecture
Children with autism are subject to the same general sleep expectations as typically developing children, and deviation from these norms is significant even when the child “doesn’t seem to need much sleep.” It is therefore important to understand the sleep patterns that typically developing children manifest at different ages.
Toddler: Ages 0 to 2 Years
Just after birth, infants lack a circadian rhythm, and their sleep/wake cycle varies without regard to dark and light cycles. During the first few months of life they develop a diurnal sleep cycle and by 9 months 70% of infants are sleeping primarily in the evening with one to two naps during the day. By age 1 year, toddlers typically require 10 to 12 hours of sleep per night and may take one or two naps of 2 to 3 hours duration during the day (Meltzer & Mindell, 2006). The most common problems at this age are night wakings, which may be as common as 42% of toddlers, and bedtime resistance (Glaze, 2004). Behavioral patterns that are established at this time can impact the child later in life, including cosleeping and developing a bedtime ritual (Glaze, 2004).
Preschool: Age 3 to 5 Years
During this period children’s sleep needs typically decrease from 13 hours to 11 hours by 5 years of age (Glaze, 2004). Napping also decreases, and children may take only one nap and for a shorter time. Night wakings become less common, with somewhere between 15 to 30% affected (Mindell & Owens, 2003). Further reinforcement of a bedtime routine is important at this age, as some children will continue to demonstrate their increasing independence through bedtime resistance. Cosleeping is a common cause of sleep disturbance at this age (Mindell & Owens, 2003).
School-age: Age 6 to 12 Years
Children of this age require approximately 10 to 11 hours of sleep and no longer require a nap. Daytime sleep may be present, although it may be a symptom of abnormal sleep patterns (Mindell & Owens, 2003; Glaze, 2004). Common issues at this age include sleepwalking, nightmares, bruxism, and sleep disordered breathing. This period is also associated with changes in circadian rhythm, and children may shift from an externally enforced sleep schedule to intrinsic preferences, e.g., morning versus evening alertness (Mindell & Owens, 2003). Children should be allowed to direct their own bedtime to some degree in order to establish a routine that fits the child’s circadian rhythm and maintains a full night of sleep (i.e., staying up later by 30 minutes is only appropriate if the child is able to alter his or her morning routine.
Adolescents: Age 12 to 18 Years
Sleep requirements drop further in this period. Most teens require approximately 9 hours of sleep per night, although the average teen gets 7 hours of sleep per night. Approximately 11 to 30% of adolescents and teenagers experience a sleep disorder at this age (Glaze, 2004). The increasing independence during these years, as well as increased responsibility at home and at school can contributed to compromised sleep. Environmental factors, such as caffeine, nicotine, alcohol, or drugs may reduce the quantity or quality of a child’s sleep, while resulting daytime sleepiness may increase the use of these substances. Further, the onset of puberty may cause changes in circadian rhythm, shifting sleep phase later by approximately 2 hours. Children in this age group in the United States are frequently getting less sleep than is needed, and insufficient sleep is a primary problem in this group.
Sleep Problems in ASD
The term “sleep problems” encompasses a variety of phenotypes, including several well-characterized sleep disorders. Although there is no official system for classifying pediatric sleep disorders, common systems have developed around the adult literature and clinical practice.
The most widely used system is the International Classi-fication of Sleep Disorders: Diagnostic and Coding Manual (American Academy of Sleep Medicine, 2005), which defines the following classes of sleep disorders: insomnia, sleep related breathing disorders, hypersomnias, circadian rhythm disorders, parasomnias, sleep related movement disorders, isolated symptoms, and other sleep disorders. Each of these classes is further subdivided based on etiology or presentation. Children with ASD most commonly present with a subset of these sleep disorders, and this chapter will focus on this subset.
The most common sleep problem experienced by children with ASD is insomnia. Over half of 167 parents surveyed with a modified Children’s Sleep Habits Questionnaire (see section on screening) reported that their child with ASD experienced insomnia 5 to 7 nights per week (Liu, Hubbard, et al., 2006). In practice, insomnia is an umbrella term that includes problems that contribute to difficulty initiating sleep or difficulty maintaining sleep. Diagnostically, the American Academy of Sleep Medicine defines insomnia as persistent difficulty with sleep initiation, maintenance, or quality that occurs despite opportunities for sufficient sleep and that results in daytime impairment (The American Academy of Sleep Medicine). In many cases the diagnosis may come from parent report rather than directly from the child. A child with insomnia may present with difficult behavior surrounding bedtime routines, impaired daytime functioning, or daytime sleepiness.
Two major contributors to insomnia are difficulty falling asleep once in bed and waking during the night. This same previously mentioned study found that the average sleep latency, or the time that it takes for a child to fall asleep once in bed, was 33 minutes, although it was reported to be as long as 150 minutes in some cases (Liu, Hubbard, et al., 2006). This large variation is supported by another study that compared parent assessment of sleep problems to objective laboratory assessment (Malow, Marzec, et al., 2006). Children who were assessed by their parents as having moderate or severe sleep problems were found to have an average sleep latency of 97 minutes. This was significantly longer than the average 30-minute sleep latency in children with ASD but mild or no sleep problems. This suggests that when sleep problems are present, difficulty initiating sleep is a common occurrence. Difficulty falling asleep is also reported as a primary concern among parents (Malow, Marzec, et al., 2006). Bedtime resistance may be a behavioral issue, related to hypersensitivity, or other problem behaviors, or it may indicate an underlying abnormality in circadian rhythm.
Another symptom of insomnia is awakening during the night. Night wakings are normal and benign in children less than six months of age, but persist in approximately 25 to 50% of children after this age (Mindell & Owens, 2003). Waking during the night is frequently a result of negative sleep associations. Children who share a bed, or who require a specific stimulus to fall asleep are more likely to wake during the night. If the stimulus, such as parent’s presence, is not available during the might then returning to sleep can be difficult. Parents may not be aware that their child wakes during the night if the child stays in his or her own room. Actigraphy can be used to assess sleep/wake patterns. A 1995 study of 39 children with autism found that night wakings were common, occurring as often as 3.2 nights per 2-week period. In nearly half of these cases the child was awake for longer than 30 minutes (Richdale & Prior, 1995).
Insomnia can be caused by a variety of different factors. The ICSD-2 divides insomnias by causative factor including adjustment insomnia, psychophysiological insomnia, paradoxical insomnia, idiopathic insomnia, insomnia due to mental disorder, inadequate sleep hygiene, behavioral insomnia of childhood, insomnia due to drug or substance, insomnia due to medical condition, and insomnia not otherwise specified (American Academy of Sleep Medicine, 2005). While insomnia is usually considered to be a disorder experienced by adults, many of these factors may be relevant to children with ASD and will be discussed.
Adjustment insomnia is marked by the occurrence of a specific stressor and is transient. The stressor may be a new environment but may also be a recent change in the child’s life that is not clearly associated with bedtime. Children with ASD may be predisposed to adjustment insomnia due to difficulties in transitions that are inherent to the disorder. Parents who mention a recent onset of insomnia should be queried about the duration and about any changes that may have taken place in the child’s life at that time. In many cases this type of insomnia will resolve on its own once the child has adjusted to a new environment.
Inadequate Sleep Hygiene
Sleep hygiene refers to the physical and behavioral environment surrounding sleep. Good sleep hygiene, or positive sleep habits, promote healthy sleep and eliminate factors that might disturb sleep. Good sleep hygiene practices include: maintaining regular and developmentally appropriate bedtimes and out-of-bedtimes; making the bedroom a media-free zone (no television, computers, video games, etc.); establishing a regular bedtime routine that is conducive to sleep (e.g., nightly bath, story, etc.); avoidance of caffeine and stimulation activity in close proximity to bedtime, and appropriate parent/caretaker expectations. Poor sleep hygiene may contribute or exacerbate sleep problems.
Behavioral Insomnia of Childhood, Limit-Setting Type
Limit-setting sleep disorder is an inability to go to sleep due to insufficient enforcement of good bedtime behaviors by parents (Mindell & Owens, 2003). In some cases parents are inconsistent with bedtime. In the absence of consistent structure, children are more likely to resist or completely refuse bedtime on any given night. This results in delayed sleep onset and shorter total sleep time, although sleep quality after onset is usual normal (Meltzer & Mindell, 2006). Children may also experience symptoms of insomnia if parents do not teach them good sleep hygiene. Allowing children to fall asleep with the television on, have access to video games after bedtime, or fall asleep in the parents bed are all examples of behaviors that will impair sleep by failing to set appropriate limits. Data published in 2006 from a survey of parents regarding their children with ASD reported that over half of the 167 participating children expressed resistance to bedtime and 16% shared a bed with parents (Liu, Hubbard, et al., 2006). This rate of cosleeping in a study with an average participant age of 8.8 years is considerably higher than a typically developing population at the same age. Limit-setting insomnia should be ruled out or identified and addressed through behavioral means in any investigation of pediatric insomnia. Particularly with cosleeping, parents may feel that falling asleep in mom or dad’s bed is acceptable if it helps a child who will not fall asleep alone. However, accommodating a child’s difficulty with bedtime either masks a potentially treatable intrinsic insomnia or causes primary insomnia. Parents should be queried about their bedtime routine with the child.
Behavioral Insomnia of Childhood, Sleep-Onset Association Type
Sleep-onset association type insomnia refers to a situation in which a child cannot fall asleep without a particular stimulus present (Meltzer & Mindell, 2006). Commonly reported negative stimuli include needing a parent present to fall asleep or needing to be driven around in the car. These behavioral accommodations are typically not sustainable and negatively impact parents’ lives to a significant degree. When the required stimulus is not present, bedtime resistance and insomnia develops. As with limit-setting insomnia, the stimulus becomes either a mask for other etiology, or it becomes an obstacle to consistent healthy sleep patterns. This behavioral disorder typically occurs in toddlers or young children, but may be present at older ages in children with developmental disorders. When identified in parent-interview, sleep-onset association disorder can be addressed with behavioral changes called extinction that will gradually wean the child off the stimulus.
Insomnia Due to Other Medical Problems
Children with ASD are at risk for other medical problems and frequently receive psychotropic medications, both of which can impact sleep. Medical problems can include gastrointestinal problems such as gastroesophageal reflux and be particularly bothersome in relation to sleep. Epilepsy, which is resent in approximately one third of children with ASD (Giovanardi Rossi, Posar, et al., 2000), may also impact sleep. Partial seizures of temporal lobe origin have been found to reduce REM sleep in adults, even when the seizures occur during the day (Bazil, Castro, et al., 2000). REM sleep has been implicated in memory consolidation and learning. The possibility that sleep problems may be secondary to an existing medical condition, as well as a review of the medications a child is receiving, deserve consideration when children with ASD are experiencing sleep problems.
Sleep disordered breathing (SDB) is a respiratory sleep disorder that involves some degree of obstruction to upper airways. SDB ranges from primary snoring to severe obstructive sleep apnea (OSA). Primary snoring does occur and can be benign, but snoring is more often a sign that OSA is present. OSA is a severe form of SDB and occurs when airflow ceases completely due to upper-airway obstruction. Signs of OSA include a repeated sequence of a snore, silence (breathing stops), and a gasp or snort as breathing resumes (Mindell & Owens, 2003). This sequence can cause small disruptions in sleep. These disruptions may be imperceptible to the patient but nonetheless fragment sleep and may result in daytime sleepiness and daytime cognitive/behavior problems including inattention and hyperactivity. Risk factors for OSA include tonsilar hypertrophy, obesity, hypotonia, family history, and ethnicity (higher in African American children; Mindell & Owens, 2003). OSA can be treated with weight-loss (when obesity is present), tonsillectomy and/or adenoidectomy, or continuous airway pressure (CPAP) when not otherwise resolved (Meltzer & Mindell, 2006). Children with ASD may have difficulty tolerating CPAP and may need a period of desensitization. Sleep disordered breathing has been reported by parents to occur in nearly 25% of surveyed children with ASD, although more data regarding the exact prevalence is needed (Liu, Hubbard, et al., 2006).
Circadian Rhythm Abnormalities
Circadian rhythm abnormalities include disruptions in the sleep-wake cycle that prohibit normal sleep. The most common type of circadian rhythm abnormality is delayed sleep phase syndrome (DSPS). This is an abnormality in circadian rhythm that results in sleep onset more than 2 hours after normal sleep time (Meltzer & Mindell, 2006). As the name implies, the child’s internal circadian rhythm is active but latent. Children with DSPS do not respond to typical cues for sleep onset, such as low light or regular bedtime, but do experience appropriate sleep duration and quality after sleep onset at a later time. The two signs of DSPS are (1) a child who falls asleep easily and consistently at a delayed hour, or (2) a child who is predictably difficult to wake the next morning, but who will wake on their own if allowed to sleep in (Meltzer & Mindell, 2006). DSPS is most often addressed with behavioral changes to the sleep-wake schedule. Specifically, the child is slowly (over a period of several weeks or months) retrained to a more appropriate sleep cycle by using the natural sleep time as a starting point and gradually moving bedtime forward.
It is unclear exactly how common DSPS is in children with ASD but it appears to occur with at an elevated prevalence from the general pediatric population. A 2008 study of regression and disturbed sleep in children with autism found that 16% of children with nonregressive autism and 35% of children with regressive onset autism had DSPS (Giannotti, Cortesi, et al., 2008). Both of these rates were significantly different from the reported 1% of typically developing controls with DSPS. Diagnosis was based on parent report questionnaire and sleep diary. Other studies support the presence and significance of this problem in children with autism. Wiggs and Stores collected sleep data from parent report, sleep diary, and actigraphy on 69 families with an ASD child (Wiggs & Stores, 1996). Of the 44 children who reported disturbed sleep, 4 experienced symptoms of DSPS. This same study found that a second circadian rhythm abnormality, irregular sleep phase syndrome, was reported in 2 of the 44 children. Additional objective studies are needed to accurately assess the prevalence of DSPS in children with ASD, but it does appear to be a prevalent complaint.
Parasomnias refer to problems that disturb sleep after it has been initiated. These include bruxism, nightmares, night terrors, sleepwalking, and REM sleep behavior disorder. Bruxism is the term used for repetitive teeth grinding during sleep. Approximately 14 to 20% of children in the general pediatric population grind their teeth during sleep, but this prevalence is likely higher in children with developmental or cognitive delays. Children are rarely aware of the condition, and parents who hear the grinding most often identify it. Bruxism can cause dental damage and may also cause muscle pain and headaches. Nightmares or frightening dreams may affect as many as 50% of young children, with decreasing prevalence as children age (Mindell & Owens, 2003). Removing negative or overstimulating images from the bedroom or practicing relaxation techniques prior to bedtime may help alleviate nightmares. Night terrors are episodes of waking during the night and expressing symptoms of intense fear. Night terrors differ from nightmares in that they occur during slow-wave sleep rather then REM sleep, generally occur earlier in the evening, and are rarely recalled by children.
Sleepwalking occurs in as many as 40% of children, and 3 to 4% experience episodes either monthly or weekly (Mindell & Owens, 2003). Sleepwalking has a strong genetic component, and a family history may be present in as many as 90% of cases. Although sleepwalking is benign, parents are able to protect the child from secondary injury by locking doors and windows, gating stairs, and removing obstructions or dangerous objects from the child’s environment. If episodes occur at predictable times, scheduled awakenings can be planned to avoid the episode. Waking the child every night 15 to 20 minutes prior to the episode for 1 to 2 weeks may resolve the problem.
REM sleep behavior disorder (RBD) is a less commonly observed parasomnia, but may be more common in children with ASD than typically developing children. During healthy REM sleep there is muscular paralysis. RBD is characterized by loss of this atonia, resulting in patients acting out dreams. Patients may kick or punch the air, run from bed, or demonstrate other complex muscle movements (American Academy of Sleep Medicine, 2005). Daytime sleepiness may be observed if sleep is fragmented as a result of RBD. In the gen eral population RBD most often occurs in adult males and is associated with neurodegenerative disease such as Parkinson’s, Alzheimer’s dementia, and multiple sclerosis. Evidence suggests that RBD may also occur at an increased incidence in children with ASD. A polysomnographic study of 11 children with a DSM-IV diagnosis of autism, ages 3 to 9 years, found that 5 met criteria for RBD (Thirumalai, Shubin, et al., 2002). RBD should be diagnosed by polysomnography, but is suggested if parents report observing any of the symptoms above. RBD may occur in combination with other sleep disorders.
As a group, parasomnias are reported to occur in approximately 53% of children with ASD. The most common parasomnia reported in this group is bruxism (18%). A reported 4% of children with ASD sleepwalk, 5% awaken during the night with inconsolable screaming, and 4% awaken from a frightening dream. Questions that may trigger identification of parasomnias are available in the CSHQ (see section on evaluation below).
Sleep Related Movement Disorders
Restless leg syndrome (RLS) is characterized by unpleasant sensations that are associated with a desire to move, and relief with such movement. These sensations occur more frequently at rest or lying down and during the evening (ICSD-2). RLS is usually considered in adults, but can have its onset in childhood. RLS is often, although not always, associated with periodic leg movement disorder (PLMD). PLMD is characterized by brief (second) jerks during non-REM sleep. These rapid movements may be accompanied by short arousals. Although the etiology of these disorders is unknown, RLS may include a history of iron-deficient anemia. Further, there appears to be a genetic component, and a family history of RLS is associated with increased risk. RLS is also associated with a diagnosis of ADHD (Mindell & Owens, 2003). RLS may be difficult to diagnosis in children with autism without polysomnography due to core deficits in communication. RLS may present as difficulty falling asleep or difficulty staying in bed at bedtime. While the diagnosis of RLS is based on clinical criteria, the diagnosis of PLMD is based on the findings of overnight polysomnography (“sleep study”), which may suggest or support the diagnosis of RLS in those children unable to provide sufficient clinical information.
The etiology of sleep problems in children with ASD is likely multifactorial, including genetic and environmental factors as well as medical and behavioral issues. Disturbances in the sleep-wake cycle may contribute to the occurrence of sleep problems in these children. The sleep-wake cycle is regulated by many factors but the primary driving force is the circadian rhythm, which is the cycle of sleep-related hormones and internal signals. Disorders of the circadian rhythm can produce sleep problems, most commonly difficulty initiating and maintaining sleep. The circadian clock is located in the suprachiasmatic nucleus of the hypothalamus and, among other things, determines the release of sleep-related hormones such as melatonin. The circadian clock, in combination with changes in light, determines the production of melatonin from the pineal gland. Bright light suppresses melatonin production, but in dim-light conditions the level of endogenous melatonin can be measured using saliva, and the time of melatonin increase, referred to as dim-light melatonin onset (DMLO), can be used as a marker for circadian rhythm. Typically the DMLO should occur just prior to average time of sleep onset. Studies indicate that melatonin regulation in children with ASD may be abnormal compared to controls. Specifically, children with ASD may have elevated melatonin levels during the day and decreased levels of melatonin at night (Ritvo, Ritvo, et al., 1993; Nir, Meir, et al., 1995; Kulman, Lissoni, et al., 2000). This pattern is the opposite from that seen in typically developing children. A 2005 study assessed 6-sulphatoxymelatonin, a primary melatonin metabolite that is excreted in urine, and found that children with ASD showed significantly lower concentrations of 6-SM relative to age- and gender-matched controls (Tordjman, Anderson, et al., 2005). These studies together suggest that circadian rhythm abnormalities may more common in children with ASD and likely contribute to disturbed sleep in children with ASD.
Sleep problems experienced by children are frequently associated with disturbances in neurocognition and behavior. In children, common consequences of poor sleep include difficulty with mood regulation and impulse control, hyperactivity or daytime sleepiness, poor concentration, and impaired memory. The impact of impaired sleep on daytime functioning may be even more severe in children with poor self-regulation, a deficit common in children with ASD. Poor sleep may exacerbate existing behavioral problems.
Data collected by the Autism Treatment Network (ATN) in 2006 found quantitative impairments in daytime functioning in children with ASD and sleep problems. Participants were 54 parents of children with a diagnosis on the autism spectrum, confirmed by ADI and ADOS. Parents reported their child’s sleep using the Children’s Sleep Habits Questionnaire (CSHQ) and completed behavioral questionnaires, including the Aberrant Behavior Checklist (ABC), the Child Behavior Checklist (CBCL), the Pervasive Developmental Disorder Behavior Index (PDDBI), and the Behavior Rating Inventory for Executive Functioning (BRIEF). Parents who reported sleep problems on the CSHQ also reported signifi cantly increased scores in several behavioral subdomains. Children were reported to have increased irritability, stereotypy, and hyperactivity, as well as deficits in executive function, including planning and organization.
These observations are consistent with reports from other studies indicating that poor nighttime sleep negatively impacts daytime functioning. In a study of children with an ADOS confirmed diagnosis of ASD and who underwent polysomnography, children with poor sleep were scored significantly higher by their caregivers on the affective problems scale of the Child’s Behavior Checklist (CBCL) than children with good sleep (Malow, Marzec, et al., 2006). A study of questionnaire data from 55 parents who self-identified as having a child with ASD (ages 5–12 years) found that children with sleep problems also had more severe autism symptoms, as assessed using the Gilliam Autism Rating Scale (Schreck, Mulick, et al., 2004). Parent-report data from a study of 32 children with Asperger’s syndrome (AS) or high functioning autism (HFA) indicates that children with AS/HFA and insomnia have more severe autism behaviors, as measured by the Autism Spectrum Screening Questionnaire, and worsened social behaviors, as assessed by the Strengths and Difficulties Questionnaire (Allik, Larsson, et al., 2006).
The majority of studies of sleep and behavior have found a statistical association, but do not provide support for a clear causal relationship, However, there is evidence that improving sleep problems improves behavior. A case study a 5-year-old female with pervasive developmental disorder not-otherwise-specified, and sleep disordered breathing found improved socialization and reduced stereotypy (Malow, McGrew, et al., 2006). Studies in typically developing children have also found improved behavior with successful treatment of sleep problems, although these results have not yet been replicated in large number in children with ASD. A study of children ages five to 13 years who underwent adenenotonsillectomy as treatment for sleep-disordered breathing found that hyperactivity was reduced in these children, and that attention improved (Chervin, Ruzicka, et al., 2006).
Sleep problems in children can also impact parents’ sleep and cause significant stress for the family. Parents of children with sleep problems are more likely to have difficulty sleeping themselves, in part due to demands placed on them by the child’s nighttime arousal. A study of 32 children with ASD and their parents found that not only did children have poorer sleep quality than a control group of 25 typically developing children, but parents of the ASD group reported significantly earlier wake times, shorter time in bed, and shorter actual sleep time than parents of the typically developing group (Meltzer, 2008). Parents of children with ASD also report higher levels of daytime stress, particularly if the child’s daytime behavior was worsened due to poor sleep. It is not clear whether there is a causal relationship between poor sleep and parental daytime stress. However, a 2001 study found that when the child’s sleep problems were successfully treated, the level of maternal stress was reduced. Paternal stress was not affected by improved sleep in the child, although father’s satisfaction with their own sleep was improved in the treatment group (Wiggs & Stores, 2001). It is possible that the relationship between child’s sleep problems and parental stress is bidirectional.
Screening and Identification
Parent report measures are a quick and easy way for clinicians to screen for sleep problems. The two most commonly used measures in the pediatric population are the Children’s Sleep Habits Questionnaire (CSHQ)(Owens, Spirito, et al., 2000a) and the BEARS. However, other instruments are available, including screening guidelines for obstructive sleep apnea (American Academy of Pediatrics, 2002). Due to the overwhelming evidence that sleep problems occur frequently in children with autism, significantly impact cognition and behavior, contribute to family stress, and may be treatable, it is imperative that all children with a diagnosis of autism spectrum disorder be assessed for the presence of comorbid sleep problems, either at the time of first diagnosis or during follow-up care.
The BEARS is a clinician-administered questionnaire that consists of five items and allows parents to report the presence of bedtime issues. These include problems with bedtime and initiating sleep, excessive daytime sleepiness, night awakenings, regularity and duration of sleep, and snoring. See below for a list of BEARS items and sample questions. These questions may be modified to best query for the child’s age and developmental level.
BEARS (Owens & Dalzell, 2005)
1. Bedtime: Does your child have any problems going to Bed or any problems falling asleep?
2. Excessive daytime sleepiness: Does your child seem Excessively sleepy during the day and/or have difficulty waking up in the morning?
3. Awakenings: Does your child Awaken during the night or have any unusual behaviors during the night?
4. Regularity and Duration of Sleep: Does your child have a Regular sleep schedule and get enough sleep each night?
5. Snoring: Does your child Snore or have any problems breathing during the night?
If parents answer yes to any of the five questions then the clinician is prompted to ask about the specifics of the problem. This instrument allows clinicians to inquire about sleep problems during a routine clinic visit, and, without being overly burdensome, will provide the clinician with some indication of need for further evaluation or for referral for formal sleep evaluation. The BEARS was developed by Judith Owens and has been used clinically since 2005 (Owens & Dalzell, 2005).
The Children’s Sleep Habits Questionnaire (CSHQ) is a parent-report questionnaire developed by Judith Owens for use in children ages 4–12 years (Owens, Spirito, et al., 2000a). Parents are asked to rate each of 33 sleep-disturbance items based on their frequency during a “typical” recent week. Behaviors are rated on a 3-point scale: “usually” if the behavior occurred 5 to 7 times per week; “sometimes” for 2 to 4 times per week; and “rarely” for 1 or fewer times per week. The CSHQ asks parents to report how often their child has experienced each of a list of specific sleep behaviors during the past 7 days, e.g., snoring. Parents are also asked to separately report whether or not the behavior was a problem. Parent responses are numerically coded and classified into eight domain scores: (1) Bedtime Resistance; (2) Sleep Onset Delay; (3) Sleep Duration; (4) Sleep Anxiety; (5) Nightwakings; (6) Parasomnias; (7) Sleep Disordered Breathing; and (8) Daytime Sleepiness. All items contribute to a composite score, which has been shown to be clinically significant. Children who have a composite sleep score greater than 41 are considered to have sleep problems and should be considered for further evaluation. The CSHQ is designed based on common clinical presentations of the sleep disorders most often seen in children, and specific answers will provide some characterization of problems that are present.
Information about the child’s sleep-wake cycle over a period of days can be collected using a sleep diary. The clinician can choose the duration of a sleep diary, but a typical period is 1 to 2 weeks. An informative sleep diary should allow parents to complete a continuous measure of their child’s sleep over the period, clearly delineating sleep and wake periods. Each 24-hour period should be recorded as fully as possible, including naps and nighttime waking (if observed by parents). Parents should also be asked to provide a daily log of their child’s routine and diet, including bedtime, consumption of caffeinated beverages, medications that might affect sleep, or any deviation from the typical routine. An example of a sleep diary is included in Figure 26-1. The sleep diary differs from other parent-report measures in that it is a structured free report rather than guided response, and because it provides more comprehensive child’s sleep over a period of days. If parents are encouraged to complete the diary diligently, it may be possible to identify variation in sleep patterns from night to night as well as provide a better understanding of the home environment and some assessment of sleep latency (if the child is put to bed at 8:00 PM but sleep does not begin until 9:00 PM).
Nighttime sleep can be assessed objectively at home by using a physical activity monitor called an actigraph. Children can wear the watch-sized actigraph on their wrist or, if necessary, on their ankle. The actigraph contains a motion sensor that records activity over a period of time, often 1 or more weeks. Data from actigraphy provides a measure of all waking and sleep time, including exact times that the child went to sleep and all naps. When combined with information regarding bedtime and out-of-bed time, this data can be used to calculate sleep latency, total sleep time, and sleep efficiency (the percent of time in bed that is spent asleep). Caregivers should be asked to complete a concurrent daily sleep diary to provide a context for the data and aid in interpretation. The most informative actigraphy data relies on compliance from both the parents and the child. Children with sensory issues may have difficulty wearing a novel object, although undergoing a period of desensitization prior to beginning data collection may help address this difficulty.
Polysomnography (PSG) is the “gold standard” for assessing sleep (Meltzer & Mindell, 2006) and provides information regarding sleep architecture and disruption. PSG combines electroencephalogram (EEG), electromyogram (EMG), and electro-oculogram (EOG), with additional assessment of respiratory activity to quantitatively describe all aspects of the child’s sleep over the course of a given night. Although PSG is widely acknowledged as the best tool for diagnosing and characterizing the sleep, and specifically sleep disorders such as PLMD and sleep disordered breathing, it has several drawbacks. Chiefly, PSG only provides data from a single or short series of nights rather than an assessment over a larger time period. The children are evaluated in the unfamiliar environment of a clinical sleep laboratory. Many children with ASD may experience difficulty tolerating the placement of the sensors and the novel environment of the sleep laboratory. Careful planning and preparation of the child and the parents are necessary for the successful completion of the polysomnographic study (Mindell, Emslie, et al., 2006).
It is critical that sleep problems be reliably identified because there are interventions available that can alleviate or cure the problems and possibly improve the consequent adverse behavioral and cognitive effects. Parents are frequently under the misconception that the sleep problems are “part of the autism” and that they cannot be treated. Both behavioral and pharmacological treatments exist and can be used in this population. Figure 26-2 presents an algorithm for screening children for sleep problems and referral for sleep evaluation or other subspecialty evaluation.
Treatment of sleep problems in children with ASD can be complicated by the many other medications and therapies that are used to treat these children. However, it is import to first manage medical and behavior problems that may contribute or exacerbate sleep problems. Specific sleep disorders such as obstructive sleep apnea should be appropriately evaluated and managed. In general, guidelines published by the American Academy of Pediatrics mandate that sleep problems should be treated first with behavioral therapy (Mindell, Emslie, et al., 2006). If problems persist, consideration can be given to use of pharmacologic sleep aids.
Sleep hygiene refers to bedtime practices, and particularly those that promote sleep onset and healthy sleep. Good sleep hygiene habits include setting a consistent and developmentally appropriate bedtime, removing electronics from the bedroom, avoiding caffeine, developing a step-down routine for bedtime and an appropriate bedtime ritual, and adjusting the environmental conditions to help entrain the circadian rhythm cycle. Low light and cool temperatures in the evening will help promote sleep onset, and bright light and warmer temperatures will help promote wakefulness. Exposure to early morning bright light helps advance the sleep phase, while evening bright light may delay sleep onset. An appropriate sleep hygiene plan should be developed in discussion with the family to meet their needs and ensure appropriate expectations. Sleep hygiene may not resolve sleep problems completely, but can contribute to improvement of the child’s sleep and may be used in concert with other behavioral and pharmacological therapies.
Specific behavioral interventions can be developed to address sleep-onset association and limit-setting type insomnia. Extinction involves putting the child to bed at a particular bedtime and then ignoring the child’s inappropriate behaviors until the following morning. This technique forces children to resolve their need for a particular stimulus on their own, although it may be unpalatable to parents. Graduated extinction allows parents to check on the child, but with increasing delay over a period of 1 to 2 weeks. As with extinction, the goal is to wean children off sleep associations that are unsustainable and teach children to “self-soothe”(Mindell & Owens, 2003). Other step-down rituals can be devised based on the child’s ability to tolerate bedtime changes and the parents desire to institute good bedtime habits. High-functioning children may respond to incentive-based interventions. In this case it is important to select incentives that are desired and that can be immediately awarded.
If behavioral therapy fails to address the child’s sleep problems, treatment with a pharmacologic agent may be indicated. Many parents treat the symptoms of their child’s sleep problem with secondary pharmacologic agents, often without a physician’s oversight. Regardless of whether the treatment is prescription or over-the-counter, a physician should work with parents to develop and oversee a good plan for pharmacologic management. However, the lack of evidence supporting most pharmacological treatments has left parents and physicians without a reliable roadmap.
The lack of attention to pharmacologic management of sleep problems in children with autism may be due to the lack of treatment studies children in general. In response to this dearth of published evidence, the AAP has identified children with ASD as a high priority population for clinical trials of pharmacologic sleep therapies (Mindell, Emslie, et al., 2006). However, several studies have been released that build on existing literature to provide evidence for several different pharmacologic treatments of sleep problems in these children. Additionally, a consensus paper was published in 2005 that reviewed commonly used pharmacologic treatments for insomnia (Owens, Babcock, et al., 2005). This statement sets forth recommendations for treatment and dosing that are based primarily on clinical experience rather than evidence based on well-designed and controlled clinical trials.
This consensus statement and other published reviews discuss prescription and nonprescription medications that are commonly used to treat insomnia. Typically these are in the class of sedatives or hypnotics, although some psychotropic medications provide secondary benefits to sleep. As yet there are no pediatric guidelines for pharmacologic management of sleep problems, and the FDA has not approved any medications labeled for treatment of pediatric sleep problems. We present here a summary of the most frequently used medications. In particular, more evidence is needed to fully assess the use of these medications in children with ASD (Mindell, Emslie, et al., 2006). Pharmacologic intervention should be initiated after a thorough sleep evaluation and should be paired with behavioral interventions.
Melatonin is an endogenous neuropetide that is secreted by the pineal gland in response to signals from the circadian clock. Typically, endogenous melatonin levels are low during the day and peak prior to nighttime sleep onset, although evidence (discussed previously in this chapter) indicates that this rhythm may be disrupted in some children with ASD. This explanation of sleep problems in this population theoretically supports treatment with exogenous melatonin, although as yet the literature has not connected a response to treatment with melatonin to an underlying melatonin abnormality. Regardless, exogenous melatonin is a commonly used over-the-counter sleep aid. Melatonin has been studied in children with ASD and found to be a safe and effective treatment for insomnia. A 2006 double-blinded, placebo-controlled cross-over trial in 11 children found that 5 mg of melatonin daily for 4 weeks significantly reduced both sleep latency and number of night wakings (Garstang & Wallis, 2006). These results have been supported by two open-label trials in children with ASD. An open-label study of the long-term safety and efficacy of melatonin was conducted in a group of 25 children with autism. Children were given 3 mg of controlled release melatonin at the start of the study, but were titrated up to as much as 6 mg per day if necessary. The study found that after 24 weeks patients had improved sleep, as evidenced by sleep diary and CSHQ. Further, children who discontinued melatonin at 16 weeks returned to disturbed sleep patterns but showed improvement after treatment resumed (Giannotti, Cortesi, et al., 2006). A large-scale clinical trial of melatonin in 107 children ages 2–18 showed that melatonin effectively resolved sleep problems in 25% of patients at doses of melatonin starting at 0.75 mg per day and titrated up to 6 mg as necessary. An additional 60% of patients reported improved sleep, although sleep problems were still present. Only three patients in this study reported experiencing side effects including morning sleepiness and increased enuresis, which resolved when the dose was lowered (Andersen, Kaczmarska, et al., 2008). Other studies have found that patients did not experience any side effects as a result of the melatonin. These studies support the use of melatonin to treat insomnia in children with ASD. Possible side effects of melatonin include hypotension, bradycardia, nausea, and headache. Melatonin may also exacerbate comorbid autoimmune diseases (Owens, Babcock, et al., 2005).
Catapres, known by the trade name of Clonidine, is an alpha-adrenergic receptor agonist that was originally developed as a nasal decongestant for adults. During initial clinical trials investigators observed that Clonidine had bradycardic and hypotensive effects, and it has since become a treatment for hypertension (Reed & Findling, 2002). Although Clonidine may cause insomnia in adults, it is soporific in children and is commonly prescribed to treat sleep problems in children with neurological disorders as well as ADHD (Reed & Findling, 2002). Clonidine may also be used to treat problems with impulsivity, inattention, and hyperactivity. Clonidine is not labeled to treat pediatric sleep problems, although studies have shown that it can improve insomnia in some children. A 1996 study found that Clonidine improved sleep problems in 85% of 62 children with ADHD, ages 4 to 17 years (Prince, Wilens, et al., 1996). Data from a 2008 open-label study of Clonidine in 19 children with ASD showed that parent report of sleep initiation improved, and that side effects were tolerable. Reported side effects from this study included lethargy, tachycardia, daytime sedation, and hypotension (Ming, Gordon, et al., 2008). These side effects were rare, and in only one case was the child withdrawn from the study due to side effects. Bradycardia, dry mouth, and depressed consciousness have also been reported (Reed & Findling, 2002).
Benzodiazepines have historically been used to treat adult anxiety disorders and as sedatives and anticonvulsants in pediatric patients. Medications in this class function as gamma-aminobutyric acid (GABA) agonists to decrease neuronal excitability across the central nervous system. A variety of structurally variant benzodiazepines are now used to help children fall asleep and stay asleep for the course of the night. In particular these medications may be used to suppress night terrors or other partial-arousal parasomnias, as well as to treat circadian rhythm disorders (Reed & Findling, 2002; Mindell & Owens, 2003). The most commonly used of this class are clonazepam (Klonopin), lorazepam (Ativan), flurazeam (Dalmane), quazepam (Doral), temazepam (Restoril), estazolam (ProSam), and triazolam (Halcion) (Reed & Findling, 2002). These medications differ primarily on time of onset, which ranges from 15 minutes to an hour, and half life, which can be 3 to 120 hours (Reed & Findling, 2002). Side effects of benzodiazepines include daytime drowsiness, a worsening of insomnia with withdrawal of the drug (rebound insomnia), other withdrawal symptoms such as phonophobia, photophobia, and seizures, as well as anterograde amnesia (Reed & Findling, 2002). Short-acting benzodiazapines are generally associated with the withdrawal effects and amnesia, while longer-acting variants are more likely to produce daytime residual effects. Clinical trials have been limited to adults and no studies exist in an ASD population. No medications in this class are FDA approved for treatment of pediatric sleep problems, and guidelines for pediatric dosing do not exist.
Zolipidem (Ambien) and Zaleplon (Sonata)
Both Zolipidem and Zaleplon are both used clinically to treat adults and adolescents with primary insomnia (Mindell & Owens, 2003). Similar to benzodiazapines, these medicines act as GABA-agonists to inhibit the central nervous system. Unlike the previous class of medications, zolipidem and zaleplon are associated with limited daytime effects and reduced tolerance. Side effects do include daytime sleepiness, confusion, anterograde amnesia, and rebound insomnia (Mindell & Owens, 2003). Results from studies in children in general are lacking, and no studies have been conducted in children with ASD.
Chloral hydrate is one of the oldest treatments for sleep problems, although its use has declined since it was introduced in the 1870s (Reed & Findling, 2002). Today chloral hydrate is used to treat sleep-onset delay and circadian rhythm abnormalities, particularly in children with neurologic abnormalities or blindness. Adult studies have not shown chloral hydrate to have a benefit over placebo in treating insomnia. Side effects include gastrointestinal distress, nausea, vomiting, liver toxicity, dizziness, light-headedness, and respirator depression (Mindell & Owens, 2003). Discontinuation after prolonged use can cause withdrawal, including seizures and delirium. Use of chloral hydrate has also been associated with adverse events, including cardiac arrhythmias and central nervous system depression in children (Reed & Findling, 2002).
Tricyclic and newer serotonergic antidepressants have been used with increasing frequency to treat partial arousals and nocturnal enuresis (Reed & Findling, 2002). Trazadone, nefazodone, and aroxetine are commonly used to treat the former, while imipramine hydrochloride is the most common antidepressant to treat the latter. These medications work by suppressing deep sleep and decreasing arousals during sleep-stage transitions. Side effects of antidepressants include daytime sleepiness and dry mouth. There is also concern for cardiac arrhythmias (Reed & Findling, 2002).
Antihistamines are the most commonly recommended nonprescription medication for sleep problems. Data published from a survey of community based pediatricians found that 68% of physicians who have recommended a nonprescription medication recommended antihistamine at least once (Owens, Rosen, et al., 2003). Nonprescription antihistamines are also commonly chosen by parents of children with sleep problems without a physician’s recommendation. H1 receptor agonists such as diphenhydramine, hydroxyzine, and chlorpheniramine act by crossing the blood-brain barrier to depress the central nervous system. Decreased alertness and slowed reaction are typically achieved 2 to 3 hours after administration, and half-life ranges from 3 to 9 hours. Side effects include impaired daytime functioning and poor sleep quality (Reed & Findling, 2002). Second- and third-generation antihistamines, such as terfenadine and loraditine, may have fewer residual daytime effects (Mindell & Owens, 2003).
Prognosis (for the Field)
Sleep problems are a frequent and serious concern in children with ASD. Numerous studies have been conducted on the prevalence of sleep problems, and the percent of children with ASD who experience difficulty sleeping ranges from between 44 and 86% (Richdale & Prior, 1995; Wiggs & Stores, 1996; Patzold, Richdale, et al., 1998; Allik, Larsson, et al., 2006). Sleep problems in this group have been consistently found to be more common than in either typically developing or developmentally delayed children. This increased risk and, even at the lowest prevalence estimates, high comorbid occurrence, put sleep problems near the top of the list of medical conditions affecting children with ASD.
Although evidence that children with autism are much more likely than typically developing children to experience disturbed sleep has accumulated over the past decade, the prevailing understanding at one time was that poor sleep was “part of the autism” and did not warrant further clinical attention. In fact, children with ASD and sleep problems may have more impaired neurocognitive functioning and worse behavior than children with ASD and normal sleep (Schreck, Mulick, et al., 2004; Malow, Marzec, et al., 2006).
In response to the high prevalence and clinical severity, sleep problems are diagnosable, often in the pediatrician’s office. Expedient screening questionnaires are available, and these can be both administered and assessed by most physicians who see children with ASD (Owens, Spirito, et al., 2000a; Owens & Dalzell, 2005). Referral to a sleep specialist may be necessary, but even in this case screening questionnaires are an efficient and effective way to identify children for further evaluation. Assessment for sleep problems should be a routine part of clinical care for children with ASD.
Available and effective treatments further justify attention to sleep problems in this population. A 2005 consensus statement provides guidelines the use of behavioral and pharmacotherapy by community-based pediatricians (Owens, Babcock, et al., 2005). Behavioral therapy should be tried first, followed by pharmacotherapy if necessary and supervised by a pediatric sleep specialist when possible. Future advancements in this field require data from well-designed clinical trials of sleep medications in children with ASD.
This review supports the opinion that sleep problems in children with ASD are a significant issue that should be part of the routine clinical evaluation of these children. Sleep problems occur frequently in ASD and negatively impact on the child’s sleep, as well as the sleep of parents and caretakers. Additionally, sleep problems negatively impact on daytime cognition and behavior of these children, and the quality of life of their families. There is a need for further characterization of specific sleep problems in ASD and comparison of differences and prevalences to children with other developmental problems and typically developing children. Effective treatment has the potential to reverse the nighttime and daytime impact of sleep problems in these children. We are challenged to develop reliable screening paradigms for the primary care physician and the ASD specialists. To develop effective treatment protocols for the sleep problems of children with ASD we need to better understand the pathophysiology and the relationship of other medical problems and medications. Well-designed clinical trials of behavioral and pharmacological therapies are necessary to establish an evidence basis for the management of sleep problems.
• Sleep problems should be part of the routine clinical evaluation of children with an autism spectrum disorder.
• Reliable screening paradigms are needed to aid primary care physicians and specialists in evaluating children with ASD.
• Well-designed clinical trials of behavioral and pharmacological therapies are needed to establish an evidence base for management of sleep problems.
• Effective management requires better understanding of the pathophysiology of sleep problems in children with ASD, including relationship to other medical problems and treatments.
• Better understanding of the epidemiology of sleep problems in children with ASD will aid identification and treatment.
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