A Practice Pathway for the Identification, Evaluation, and Management of Insomnia in Children and Adolescents With Autism Spectrum Disorders

AUTHORS: Beth A. Malow, MD, MS,a,b,c Kelly Byars, PsyD,d abstract Kyle Johnson, MD,e Shelly Weiss, MD,f Pilar Bernal, MD,a,c Suzanne E. Goldman, PhD,g Rebecca Panzer, MA, RD, LD,h OBJECTIVE: This report describes the development of a practice path- Daniel L. Coury, MD,i and Dan G. Glaze, MDj way for the identification, evaluation, and management of insomnia in Departments of aNeurology and bPediatrics and cKennedy Center, children and adolescents who have autism spectrum disorders (ASDs). Vanderbilt University Medical Center, Nashville, Tennessee; METHODS: The Sleep Committee of the Autism Treatment Network dDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Hospital Children’s Medical Center, (ATN) developed a practice pathway, based on expert consensus, to Cincinnati, Ohio; eDepartment of Psychiatry, Oregon Health and capture best practices for an overarching approach to insomnia by Science University, Portland, Oregon; fHolland Bloorview Kids a general pediatrician, primary care provider, or autism medical spe- Rehabilitation Hospital, Toronto, Ontario, Canada; gKaiser h cialist, including identification, evaluation, and management. A field Permanente Northern, San Jose, California; MassGeneral Hospital for Children, Boston, Massachusetts; iDepartment of test at 4 ATN sites was used to evaluate the pathway. In addition, a sys- Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio; and tematic literature review and grading of evidence provided data jDepartments of Neurology and Pediatrics, Baylor College of regarding treatments of insomnia in children who have neurodevelop- Medicine, Houston, Texas mental disabilities. KEY WORDS actigraphy, education, sleep, sleep latency RESULTS: The literature review revealed that current treatments for ABBREVIATIONS insomnia in children who have ASD show promise for behavioral/ ASD—autism spectrum disorder educational interventions and melatonin trials. However, there is ATN—Autism Treatment Network a paucity of evidence, supporting the need for additional research. CSHQ—Children’s Sleep Habits Questionnaire NICHQ—National Initiative for Children’s Healthcare Quality Consensus among the ATN sleep medicine committee experts RCT—randomized controlled trial included: (1) all children who have ASD should be screened for This manuscript has been read and approved by all authors. insomnia; (2) screening should be done for potential contributing This paper is unique and not under consideration by any other factors, including other medical problems; (3) the need for publication and has not been published elsewhere. therapeutic intervention should be determined; (4) therapeutic www.pediatrics.org/cgi/doi/10.1542/peds.2012-0900I interventions should begin with parent education in the use of doi:10.1542/peds.2012-0900I behavioral approaches as a first-line approach; (5) pharmacologic Accepted for publication Aug 8, 2012 therapy may be indicated in certain situations; and (6) there should Address correspondence to Beth Malow, MD, MS, Burry Chair in be follow-up after any intervention to evaluate effectiveness and Cognitive Childhood Development, Director, Vanderbilt Sleep tolerance of the therapy. Field testing of the practice pathway by Disorders Division, 1161 21st Avenue South, Room A-0116, Nashville, TN 37232. E-mail: [email protected] autism medical specialists allowed for refinement of the practice PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). pathway. Copyright © 2012 by the American Academy of Pediatrics CONCLUSIONS: The insomnia practice pathway may help health care FINANCIAL DISCLOSURE: The authors have indicated they have providers to identify and manage insomnia symptoms in children and no financial relationships relevant to this article to disclose. adolescents who have ASD. It may also provide a framework to evaluate the impact of contributing factors on insomnia and to test the effec- tiveness of nonpharmacologic and pharmacologic treatment strategies for the nighttime symptoms and daytime functioning and quality of life in ASD. Pediatrics 2012;130:S106–S124

S106 MALOW et al Downloaded from www.aappublications.org/news by guest on October 2, 2021 SUPPLEMENT ARTICLE

Approximately 1 in 110 children fulfills Despite the prevalence of and morbidity once child is falling asleep easier; and the Diagnostic and Statistical Manual associated with pediatric insomnia, scheduled awakenings: awakening the of Mental Disorders, Fourth Edition, thereisevidencethatsleepdisordersin child before a spontaneous awakening. Text Revision, diagnostic criteria for children often go undetected and un- Extinction and parent education have autism spectrum disorders (ASDs) treated.12–14 Medical practitioners of- strong empirical support whereas the as defined by delayed or abnormal ten do not ask about sleep concerns or other interventions are less confidently social interaction, language as used in parents do not seek assistance.15 Many supported.18 To our knowledge, how- social communication, and/or restricted parents have poor knowledge about ever, there are no published guidelines repetitive and stereotyped patterns sleep development and sleep prob- related to management of insomnia of behavior, interests, and activities.1 lems.16 This is particularly relevant to in children who have ASD, including Children who have ASD are at greater children who have ASD, in that parents screening and treatment. The evidence risk for developing sleep problems than may present to the pediatrician with that children who have ASD are at typically developing children. Research concerns regarding aggression, im- greater risk for insomnia and its has documented that the prevalence of pulsivity, inattention/hyperactivity, or morbidity suggests that sleep screen- sleep disturbances ranges from 53% to other behavioral issues that may be ing in this population of children is 78% for children who have ASD com- secondary to a sleep disorder. The extremely important. The ideal evalua- pared with 26% to 32% for typically de- contribution of the sleep disorder may tion of insomnia in children who have veloping children.2,3 be undetected due to emphasis on ASD involves a comprehensive sleep The key components of pediatric in- treating the behavioral issue as op- assessment, as outlined in a recent somnia are repeated episodes of dif- posed to identifying and treating the review.22 ficulty initiating and/or maintaining underlying factors. This deemphasis of To facilitate the evaluation of children sleep, including premature awaken- underlying factors may be due to the with ASD for insomnia, the Autism Treat- ings, leading to insufficient or poor- absence of a standardized approach ment Network (ATN) in association with quality sleep. These episodes result in for recognition and treatment of in- the National Initiative for Children’s functional impairment for the child or somnia in children who have ASD. Healthcare Quality (NICHQ) worked col- other family members.4 In typically Guidelines exist for sleep screening and laboratively to develop the clinical developing children, the primary cause intervention in typically developing practice pathway presented in this arti- of insomnia is behaviorally based.5 In children.17,18 Guidelines and empirical cle. The intention of this clinical practice the ASD population, however, insomnia support also exist for the effectiveness pathway is to emphasize the need for is multifactorial. It includes not only of behavioral treatment of bedtime screening of sleep problems in ASD and behavioral issues but also medical, problems and night wakings in chil- to provide a framework for decision- neurologic, and psychiatric comorbid- dren.18–21 Specific behavioral treat- making related to best practices in the ities; it is also an adverse effect of the ments supported include the following: care of children and adolescents with medications used to treat symptoms of unmodified extinction: leaving the ASD in primary care settings, when seen 6 autism and these comorbidities. child’s bedroom after putting the child by a general pediatrician, primary care Typically developing children who have to bed and not returning until morning provider, or autism medical specialist. insomnia are at increased risk for unless the child is ill or at risk for in- The pathway is not intended to serve as neurobehavioral problems such as jury; extinction with parent presence: thesolesourceofguidanceintheeval- impairments in cognition, mood, atten- parent is present in the room with the uation of insomnia in children who have – tion, and behavior.5,7 9 Similar to the child but does not interact with him ASD or to replace clinical judgment, and behavioral morbidity associated with or her; graduated extinction: parent it may not provide the only appropriate ’ pediatric insomnia that is observed in returns to childs bedroom to attend approach to this challenge. the general population, children who to child on request or agitation but have ASD and sleep problems are prone increases the time in between requests METHODS to more severe comorbid behavioral by the child for the parent to return; disturbances compared with children preventive parent education: providing Guideline Development without sleep disturbances.10 In addition, education to parent on sleep habits The ATN Sleep Committee consists of treating insomnia in children who have and bedtime routine; bedtime fading: pediatric sleep medicine specialists as neurodevelopmental disorders may im- delaying bedtime to promote sleep and well as developmental pediatricians, prove problematic daytime behaviors.11 then “fading” or advancing bedtime neurologists, and psychiatrists. The

PEDIATRICS Volume 130, Supplement 2, November 2012 S107 Downloaded from www.aappublications.org/news by guest on October 2, 2021 clinical practice pathway was designed diagnosed with ASD (questions and updates, understand variance, and re- to assist primary care providers and search terms available on request from commend changes. Working with the others working directly with families the authors). We searched OVID, CINAHL, NICHQ, members of the ATN Sleep affected by ASD in addressing the chal- Embase, Database of Abstracts and Re- Committee refined and finalized the lenge of insomnia with regard to iden- view Database of Abstracts of Reviews practice pathway on the basis of feed- tification,assessment,andmanagement. and Effects, and the Cochrane Database back from the pilot sites. In response to Insomnia was defined as “repeated of Systematic reviews databases, with recommendations from the pilot sites difficulty with sleep initiation, duration, searches limited to primary and sec- to increase feasibility, the NICHQ also consolidation, or quality that occurs ondary research conducted with developed a 1-page checklist designed despite age-appropriate time and op- humans, published in the English lan- to guide providers through the practice portunity for sleep that results in day- guage, involving children aged 0 to 18 pathway (Fig 2). time functional impairment for the years, and published between January child and/or family.”18 The responses of 1995 and July 2010. Individual studies RESULTS were graded by using an adaptation the parents to selected questions on Results of the Literature Review the Children’s Sleep Habits Question- of the GRADE system24 by 2 primary fi naire (CSHQ)23 identified those patients reviewers and then reviewed by content The search identi ed 1528 articles. Af- who have insomnia. experts for consensus. Discrepancies ter removing review articles, com- were resolved by a third party. mentaries,casestudieswithfewer than After performing a systemic review of 10 subjects, studies that included chil- the literature, expert opinion and con- dren who did not have ASD, non- sensuswasusedtoformthebasisofthe Pilot Testing of the Pathway intervention trials, and articles that practice pathway (Fig 1). The ATN Sleep The ATN selected 4 pilot sites (Baylor did not address our target questions, Committee’s knowledge of the litera- University, Houston, Texas; Oregon 20 articles remained (Table 1). We ture and applicability to clinical prac- Healthand Science University, Portland, reviewed the literature for studies re- tice informed best practices, which in Oregon; Kaiser Permanente Northern, lated to other aspects of the practice turn created an overarching approach San Jose, California; University of Mis- pathway (eg, screening for insomnia, to insomnia within ATN sites by the souri, Columbia, Missouri) to test the identifying comorbidities, importance autism medical specialist. feasibility of the practice pathway and of follow-up) in the ASD population provide information regarding needed and were unable to identify evidence- Systematic Review of the Literature modifications. The pilot sites collected based reports for aspects other than We conducted a systematic literature data to document adherence to the treatment. A comprehensive review25 review to find evidence regarding practice pathway and participated in and consensus statement26 related the treatment of insomnia in children monthly conference calls to provide to the pharmacologic management of

FIGURE 1 Checklist for carrying out the practice pathway in children who have ASD and insomnia. CSHQ, Children’s Sleep Habits Questionnaire.

S108 MALOW et al Downloaded from www.aappublications.org/news by guest on October 2, 2021 SUPPLEMENT ARTICLE

FIGURE 2 Practice pathway for insomnia in children who have ASD.

PEDIATRICS Volume 130, Supplement 2, November 2012 S109 Downloaded from www.aappublications.org/news by guest on October 2, 2021 S110

TABLE 1 Results of Systematic Literature Review

AO tal et MALOW Study and Grade Sample Intervention and Duration Measures Used to Arrive at Results Conclusions Conclusion Pharmacologic interventions Aman et al, 200541 Included: 101 children aged 5 to 17 y 16 wk (nonresponders) to Parent report sleep log Sleep problems and anxiety less Risperidone improves sleep from Research Units on 6 mo (responders) given common in risperidone group latency in children with ASD Pediatric Psychopharmacology placebo or risperidone (P = .02; P = .05). Average sleep but not sleep duration; high Network with ASD duration increased short-term rates of adverse outcomes (17 min; 40 min) but not beyond

Downloaded from 6 mo (29 min). Adverse events scored as moderate (placebo versus risperidone, respectively): somnolence (12% vs 37%), enuresis (29% vs 33%), excessive appetite (10% vs 33%), rhinitis (8% vs 16%),

www.aappublications.org/news difficulty waking (8% vs 12%), and constipation (12% vs 10%) RCT, level II Excluded: Mental age ,18 mo, 20 to 44.9 kg = 0.5 mg up to Abnormal Involuntary positive b-human chorionic maximum of 2.5 mg/day Movement Scale gonadotropin test result for girls, significant medical condition, previous trial with risperidone, history of neuroleptic malignant syndrome, and/or weight ,15 kg , 20 kg = similar, except Adverse events scored as $ byguest on October2,2021 slower dosing 45 kg mild or moderate/severe started at 0.5 mg nightly (parent report) then titrated to a maximum of 3.5 mg/day in divided doses Honomichl et al, 200242 Included: 17 children aged 3 to 8 y 4 wk placebo and 4 wk CSHQ Secretin did not significantly affect Secretin does not significantly with autism recruited as subset intervention 2 CU/kg CSHQ scores: Bedtime improve sleep-onset delay, of larger study (California) porcine secretin resistance (Pre, mean: 9 [range: duration, bedtime resistance, intravenously; no 6–17]; Post, mean: 8 [range: 6–13]) and night wakings in children washout with ASD RCT, level III Excluded: not specified Sleep diary (bedtime, sleep Sleep-onset delay (Pre, mean: 2.1 onset, time/duration night [range: 1–3]; Post, mean: 1.6 waking, morning rise) [range: 1–3]) Night wakings (Pre, mean: 4.1 [range: 3–7]; Post, mean: 3.6 [range: 3–5]) Sleep duration (Pre, mean: 4.7 [range: 3–7]; post, mean: 4.3 [range: 3–8]) EITISVlm 3,Splmn ,Nvme 2012 November 2, Supplement 130, Volume PEDIATRICS TABLE 1 Continued Study and Grade Sample Intervention and Duration Measures Used to Arrive at Results Conclusions Conclusion

Ellaway et al, 200143 Included: experimental group 100 mg/kg liquid L-carnitine Rett syndrome Symptoms Compared with Rett syndrome L-carnitine supplementation consisted of 21 females aged 7 to twice a day for 6 mo Severity Index controls, L-carnitine improves sleep efficiency but 41 y; recruited from previous significantly improved sleep not duration, latency, daytime 8-wk trial; control group included efficiency (P , .03) but not sleep, or number of night 62 females aged 4 to 30 y duration (P = .57), latency wakings in children with Rett recruited from Australian Rett (P = .15), daytime sleep (P = .55), syndrome Syndrome Register or night wakings (P = .25)

Downloaded from Pre/post-control, Excluded: Not specified SF-36 Health Survey level III Hand apraxia scale 7-d sleep diary TriTrac-R3D Ergometer (Hemokinetics, Inc, Madison www.aappublications.org/news Wisconsin) Posey et al, 200144 Included: 26 children and young Mirtazapine starting dose of Clinicians used the CGI scale to Nine participants responded (defined Mirtazapine is effective in adults, aged 3 to 23 y with ASD 7.5 mg daily with dosage rate severity and according to a CGI score of much improving sleep quality in (Indiana); 20 had comorbid increases made in 7.5-mg improvement. A modified CGI improved or very much children with ASD intellectual disability. Mirtazapine increments up to a improvement item improved). Five of 9 responders was prescribed to target maximum of 45 mg daily assessing sleep quality was showed improved sleep. Of 17 symptoms of aggression, self- in divided doses, based also included nonresponders, 3 showed injury, irritability, anxiety, on response of target improved sleep. Statistically depression, insomnia, and symptoms and side significant improvement was interfering repetitive behavior effects (range: 7.5–45 seen on the CGI severity ratings

byguest on October2,2021 mg). Treatment duration of sleep (P = .002) ranged from 11 to 368 d (mean duration: 150 6 103 d) Pre/post-no Excluded: Not specified control, level III Rossi et al, 199945 Included: 25 children aged 2 to 20 y Niaprazine 1 mg/kg per day Behavioral Summarized Compared with start of the treatment, Niaprazine is effective in with ASD (University of Bologna) TID for 60 d Evaluation (included sleep Behavioral Summarized improving sleep latency and with continuous presence ($1y) disorders; difficulty falling Evaluation showed night wakings in childrenwith of severe mood disorders, asleep, night wakings, and improvement in sleep disorders ASD aggressiveness, and early waking. Scored 0 to 4 by the end of the trial (P , .001) hyperkinesia (absent to very severe) Pre/post-no Excluded: children nosographically control, level III defined congenital or acquired encephalopathy ARTICLE SUPPLEMENT Ming et al, 200846 Included: 19 children aged 4 to 16 y Clonidine 1 time per day, Caregiver report (average Sixteen of 17 children experienced Clonidineimprovessleeplatency with ASD (New Jersey) and sleep initial dose 0.05 mg and bedtime, latency, number of improved sleep initiation (2–5h and wakings in children with and behavioral disorders gradually advanced to 0.1 wakings) before and during before treatment, 0.5–2h developmental disorders mg; oral tablet. Duration treatment during treatment); 16 of 17 with for 6 mo to 2 y sleep maintenance disorders experienced improvements; 5 S111 still experienced night wakings S112

TABLE 1 Continued

AO tal et MALOW Study and Grade Sample Intervention and Duration Measures Used to Arrive at Results Conclusions Conclusion Retrospective Excluded: not specified case control, level III Other biologic agents Adams and Holloway, 200447 Included: 25 children aged 3 to 8 y Days 0 to 24: 1/8 dose of SS-II CGI Sleep and gastrointestinal symptoms Moderate-dose multivitamin with ASD with no changes in (standard multivitamin), as evidenced by CGI score (including vitamin B6 and treatment therapies in previous 2 increased linearly to improved compared with vitamin C) may have

Downloaded from mo, and no previous use of maximum placebo (P = .03) a positive impact on CGI sleep multivitamin supplements other score in children with ASD than standard children’s multivitamin (Arizona) RCT level II Excluded: not specified Days 25 to 34: held maximum Blood and urine sample (plasma dose of SS-II B6, pyridoxine, pyridoxal,

www.aappublications.org/news pyridoxamine, a2lipoic acid, vitamin C) Days 35 to 50: gradual transition to SS-III Days 50 to 90: continued SS-III; full dose 1 ml/5 lb TID with food for a total daily intake of 3 ml/5 lb body weight Dosman et al, 200748 Included: 33 children aged 2 to 5 y 6 mg elemental iron/kg Sleep Disturbance Scale for Per the sleep disturbance scale Oral iron supplementation

byguest on October2,2021 diagnosed with autism with per day for 8 wk Children scores, restless sleep improved improves restless sleep in ferritin measured previously significantly (29%; P = .04) and childrenwithASDbutdoesnot (Toronto) 35% had improved sleep affect irritability, sleep latency; no relation was found latency, or periodic leg with ferritin (P = .61), irritability movements (P = .83), or Periodic Leg Movements During Sleep Scale (P = .82) Pre/post-control, level II Excluded: currently taking iron If not tolerated, received Periodic Leg Movements Mean ferritin and MCV increased supplementation 60 mg/day of During Sleep Scale significantly (16 to 29 mg/L) microencapsulated powdered elemental iron Blood sample (MCV, mercury, albumin, vitamin B12, serum ferritin, transferrin) EITISVlm 3,Splmn ,Nvme 2012 November 2, Supplement 130, Volume PEDIATRICS TABLE 1 Continued Study and Grade Sample Intervention and Duration Measures Used to Arrive at Results Conclusions Conclusion Wright et al, 201149 Included: 20 children, aged 4 to 16 y Melatonin 2 mg, 30 to 40 min Daily sleep diaries (time Mean sleep latency was lower Melatonin improves sleep with ASD and prolonged sleep before planned sleep, or melatonin taken, bedtime, (P = .004) and total sleep time was latency and total sleep time in latency, excessive night waking, placebo and then crossed sleep time, night wakings, longer (P = .002) during children with ASD but not and/or reduced total sleep time. over to the other agent. time awake) were collected melatonin treatment compared night wakings Children had undergone behavior The dose was increased every month for 9 mo with placebo. Night wakings did management that was not by the parent every 3 not improve (P = .2) successful and were free of nights by 2 mg to

Downloaded from psychotropic medications a maximum dose of 10 mg until “good” sleep was achieved, defined as an improvement of $50%. Treatment phase lasted 3 mo for each agent with www.aappublications.org/news a 1 mo washout RCT, level III Excluded: children previously or Sleep difficulties questionnaire Dyssomnia subscale improved with currently on melatonin, those treatment (P = .04) but not currently on psychotropic parasomnia, sleep apnea, or medications, and those with other other sleep disorders neurodevelopmental disorders such asFragile X orRettsyndrome Garstang and Wallis, 200627 Included: 7 children aged 4 to 16 y Placebo or 5 mg melatonin Parental sleep charts (total Baseline, placebo, and melatonin Melatonin is an effective withautismandsleepingdifficulty for 4 wk, washout 1 wk, sleep time, sleep latency, values respectively: Sleep treatment to improve sleep (at least 1 h sleep latency and/or then reversed for 4 wk night wakings, morning latency improved 1.54 h versus latency number of night

byguest on October2,2021 night waking 4 times per week for awakening) baseline (2.6 h [CI: 2.28–2.93]; wakings and sleep duration the last 6 mo) (United Kingdom) 1.91 h [CI: 1.78–2.03]; 1.06 h [CI: 0.98–1.13]) RCT, level II Excluded: children previously/ Wakings per night decreased by 0.27 currently using melatonin and/or per night versus baseline taking sedative medications for (0.35 [CI: 0.18–0.53]; 0.26 ,4wk [CI: 0.20–0.34]; 0.08 [CI: 0.04–0.12]) Duration increased by 1.79 h versus baseline (8.05 h [CI: 7.65–8.44]; 8.75 h [CI: 8.56–8.98]; 9.84 h [CI: 9.68–9.99]) UPEETARTICLE SUPPLEMENT S113 S114 TABLE 1 Continued Study and Grade Sample Intervention and Duration Measures Used to Arrive at Results Conclusions

AO tal et MALOW Conclusion Wirojanan et al, 200928 Included: 18 children aged 2 to 15 y Placebo or 3 mg melatonin Sleep diary (sleep latency, Compared with placebo, sleep Melatonin is an effective with autism and/or Fragile X given 30 min before duration,sleeponset,number duration improved in 9 of 12 treatment to improve sleep syndrome who reported sleep bedtime for 2 wk, then of night wakings) participants by 21 min (P = .057; duration, sleep latency, and problems (California) reversed for 2 wk (no effect size: 2.12), sleep latency sleep onset time but not night washout) improved in 11 of 12 wakings participants by 28 min (P = .10; effect size: 1.79), sleep onset improved by 42 min (P = .017; effect size: 2.80), and Downloaded from awakenings were improved by 0.07 but were insignificant (P = .73; effect size: 0.3540) RCT level II Excluded: not specified Actiwatch (Philips Respironics, Bend, Oregon) Paavonen et al, 200350 Included: 15 children 5 to 17 y Received 3 mg of melatonin Children’s Self-Report for Sleep Melatonin improved nocturnal Melatonin is an effective www.aappublications.org/news diagnosed with Asperger’s 30 min before bed for 14 d Problems activity (31.39 6 7.86 to 18.74 6 treatment to improve syndrome and severe sleep 4.99; P = .041) and sleep latency nocturnal activity and sleep problems in last 3 mo (Helsinki) (from 40.02 6 24.09 to 21.82 6 latency but not night wakings, 9.64; P = .002) but increased sleep efficiency, or duration in number of wakings (from 15.14 6 children with Asperger’s 6.12 to 17.85 6 6.25; P = .048). syndrome No significant changes were found in sleep efficiency (85.13 6 5.57 to 86.03 6 4.62; P = .331) or duration (477.40 6 55.56 byguest on October2,2021 to 480.48 6 50.71; P = .572). Pre/post-control, Level II Excluded: children taking Sleep Disturbance Scale for psychotropic medications or Children with major psychiatric comorbidity CBCL Karolinska Sleepiness Scale Teacher’s Daytime Sleepiness Questionnaire Actigraphy EITISVlm 3,Splmn ,Nvme 2012 November 2, Supplement 130, Volume PEDIATRICS TABLE 1 Continued Study and Grade Sample Intervention and Duration Measures Used to Arrive at Results Conclusions Conclusion Giannotti et al, 200651 Included: 25 children aged 2.6 to 9.6 y 6- to 24-mo (n = 25 and CSHQ CSHQ values from baseline to 6 mo Melatonin is an effective with autism and CARS score n = 16, respectively) were significantly improved (65 treatment to improve sleep ,29.5 with sleep disorder (.45 study vs 43; P , .001). CSHQ values duration, latency, number of min sleep latency, .3 times per regarding latency, duration, night wakings, and bedtime week night wakings, and waking resistance, anxiety, night resistance in children with before 5 AM .3 times per week) wakings, and daytime ASD (Italy) sleepiness were significantly

Downloaded from improved (P , .001). Sleep- disordered breathing also improved (P , .01). Sleep diaries showed improvements in duration by 2.6 h (P , .001), awake time after sleep onset by www.aappublications.org/news from 70 to 10 min (P , .001), cosleeping in 55% (P , .001), parental presence at bedtime in 63% (P , .001), and bedtime irregularity in 61% (P , .001). Those who continued 24 mo showed significant improvement in CSHQ scores in years 1 and 2 (63 vs 44 vs 44; P , .001)

byguest on October2,2021 Pre/post-control, level II Excluded: children with autism 3 mg controlled-release Sleep diary (bed time, rise time, diagnosis but with CARS score melatonin 30 to 40 min duration, night wakings and below cutoff, coexisting before bedtime (1 mg FR duration, day naps) conditions, and/or taking and 2 mg CR) medications for 6 mo previously Childrenadvisedtogive2mg FR is children awoke for .15 min during the night Physician could increase dose to maximum of 4 mg in children aged ,4 y and up to 6 mg in children aged .4y Malow et al, 201152 Included: 24 children aged 3 to 9 y Two-week acclimation Actigraphy; CSHQ With melatonin treatment (compared Melatonin is an effective with ASD and sleep-onset delay of phase: inert liquid 30 min with acclimation phase), treatment of sleep latency, ARTICLE SUPPLEMENT $30 min on $3 nights per week before bedtime statistically significant and improves aspects of improvements were seen in daytime behavior and sleep latency (42.9 to 21.6 min; parenting stress in children P , .0001) but not total sleep with ASD. It is safe and well time or wake time after sleep onset tolerated S115 S116 TABLE 1 Continued Study and Grade Sample Intervention and Duration Measures Used to Arrive at Results Conclusions

AO tal et MALOW Conclusion Pre/post-control, Level II Excluded: children with epilepsy or Optional escalating dose CBCL, RBS, PSI. Laboratory Significantly significant taking psychotropic medications. protocol based on 3-wk findings (CBC, metabolic improvements were also Before melatonin treatment, periods. Dose was profile including liver and noted in CSHQ subscales of medical comorbidities were escalated from 1 mg to 3 renal function, corticotropin, sleep-onset delay and sleep addressed, and parents received mg to 6 mg based on cortisol, estrogen, duration, CBCL subscales of sleep education training response (if a satisfactory testosterone, FSH, LH, and withdrawn, attention-deficit/ response occurred, prolactin). Hague Side Effects hyperactivity, and affective, defined as falling asleep Scale RBS stereotyped and within 30 min on $5 compulsive, and the Difficult Downloaded from nights per week by Child subscale on the PSI. No actigraphy, the dose was change in laboratory findings. not escalated) Loose stools in 1 child; no other adverse effects Andersen et al, 200830 Included: 107 children aged 2 to 18 y Aged ,6 y, .75-1 mg Chart review of clinic notes After initiation, 25% with sleep Melatonin is a safe, effective diagnosed with autism previously melatonin 30 to 60 min (including sleep hygiene, problems no longer a concern; treatment to reduce www.aappublications.org/news recommended to take melatonin before bed. After 2 wk, if other psychiatric conditions, 60% had improved sleep but sleep problems in sleep disorder (Tennessee) no response, increased severity of ASD, use of still had concerns; for children with ASD by 1 mg every 2 wk up to medications) 13% sleep problems remained 3mg a major concern, and 1% reported worse sleep after treatment. Three children had adverse effects (morning sleepiness and/or increased enuresis) Pre/post-No control, Excluded: children with a diagnosis Aged $6 y, 1.5 mg melatonin Sleep diary byguest on October2,2021 level III of bipolar disorder 30 to 60 min before bed time If no response, increased dose to 3 mg after 2 wk All children: if no response after 4 wk, increase dose to 6 mg Behavioral/educational interventions Reed et al, 200931 Included:20familiesofchildrenaged • Three 2-h sessions for 3 CSHQ Educational intervention showed Educational intervention with 3 to 10 y with clinical diagnosis of consecutive weeks; improved CSHQ scores for parents improves bedtime ASD with sleep concerns follow-up 1 mo after end bedtime resistance (P = .001), resistance, latency, duration, (Tennessee) latency (P = .004), duration andsleepanxietybutnotnight (P = .003), and sleep anxiety wakings, early morning (P = .022) but not night wakings waking, parasomnias, sleep (P = .508), parasomnia (P = .607), disordered breathing, or sleep-disordered breathing daytime sleepiness in (P = .625), and daytime children with autism sleepiness (P = .096) EITISVlm 3,Splmn ,Nvme 2012 November 2, Supplement 130, Volume PEDIATRICS TABLE 1 Continued Study and Grade Sample Intervention and Duration Measures Used to Arrive at Results Conclusions Conclusion Pre/post-no control, Excluded: children with primary Session 1: established Actigraphy Actigraphy showed improved sleep level II sleep disorders such as sleep daytime and night time latency (62.2 6 33.33 min vs apnea, narcolepsy, and habits and a bedtime 45.6 6 27.6; P = .039) but not neurologic/medical conditions routine based on FISHand waking after sleep onset that may contribute to disordered CSHQ (24.56 9.8 vs 32.2 6 24.7 min; sleep P = 1.0) Session 2: Strategies to Latency, duration, night 71% of parents reported fewer nights

Downloaded from minimize night waking wakings cosleeping; 33% reported and early morning improvement in early morning waking waking Session 3: address individual sleep concerns www.aappublications.org/news Weiskop et al, 200532 Included: 13 children (across Five sessions over 7 wk with Sleep Diary (behavior, lights out, Baseline compared with intervention: Educational intervention with 13 families) aged 5 y with weekly telephone calls; sleep onset, waking, 4.6% moderate deterioration of parents improved sleep either Fragile X syndrome follow-up at 3 and 12 mo cosleeping, morning wake sleep behaviors, 25% no change, latency and night wakings but (n = 7) or ASD (n = 6) with time) 29.7% moderate improvement, not duration in children with perceived sleep difficulty and 40.6% substantial developmental disabilities (Australia) improvements Case series, level III Excluded: excluded if diagnosed Session 1: goal setting Baseline compared with 3 mo: with epilepsy and/or if 1.6% substantial deterioration, diagnosed with ASD, were 4.8% moderate deterioration, not to be taking medication 27% no change, 23.8%

byguest on October2,2021 moderate improvement, and 41.3% substantial improvement Session 2: learning theory; Baseline compared with 12 mo: antecedents and 7.7% moderate deterioration, consequences. Created 19.2% no change, 26.9% intervention with moderate improvement, reinforcement and visual and 46.2% substantial representation improvement Session 3: effective Sleep latency improved in 6 of 10 (60%) instructions and partner support strategies Session 4: extinction Night waking improved for 7 of 10 (70%) techniques Session 5: review session Duration was variable and unchanged ARTICLE SUPPLEMENT Cosleeping was also 100% of parents reported improved addressed sleep but 50% still considered sleep an issue S117 S118 TABLE 1 Continued Study and Grade Sample Intervention and Duration Measures Used to Arrive at Results Conclusions

AO tal et MALOW Conclusion Complementary and alternative medicine Piravej et al, 200933 Included: 60 children aged 3 to 10 y Two 60-min standard SI or Sleep diary Massage improved sleep scores (11.5 vs TT, before bedtime improves diagnosed with autism; 30 were Two 60-min TTM and SI for 5.3; P , .001). Standard SI sleep in children with ASD but put into control group (SI) and 30 8wk improved sleep behavior (13.9 not more than compared with were experimental (SI + TTM) vs 8.2; P , .001). The difference standard SI (Thailand) between pre- and post-sleep behavior scores of the control and massage groups were not Downloaded from statistically significant (5.7 vs 6.3 respectively; P = .85) RCT, level II Excluded: those with Two 60-min TTM and SI contraindications for TTM and for 8 wk those unable to complete 80% of treatment (13 massages) www.aappublications.org/news Williams, 200634 Included: 12 children aged 12 to 15 y Three administrations of Sleep diary recorded by staff on Participants did not demonstrate Aroma therapy is not an effective diagnosed with ASD from aroma therapy (2% 30-min interval rounds (sleep statistically significant sleep- treatment to affect sleep a residential school for children lavender oil in grape seed onset, duration, wakings) onset time (F = 1.27; df = 4.15, 41.5; onset, duration, and night with autism (United Kingdom) oil) over 24 d via massage P = .30). Night wakings did not wakings of foot and leg ∼2 hours differ with and without before bed aromatherapy (x2 = 20.19; df = 16; P = .21). Sleep duration was not affected by aromatherapy (F = 0.59; df = 16, 160; P , .89) byguest on October2,2021 Case series level II Excluded: none specified Escalona et al, 200135 Included: 20 children aged 3 to 6 y For 1 mo, received 15-min Sleep diaries (fussing, Greater declines for the massage Massage before bed decreases recruitedfromschool forchildren massage therapy by restlessness, crying, self- therapy group with regard to fussing/restlessness, crying, with autism (Florida) parents (trained by stimulating behavior, and fussing/restlessness, crying, self-stimulating behavior, and therapist) or 15 min of number of times child left the self-stimulating behavior, and getting out of bed in children reading before bedtime bed) getting out of bed (actual with ASD more than reading numbers not provided; only provided statistics for day-time behavior) RCT, level IV Excluded: not specified CARS, Childhood Autism Rating Scale; CBC, complete blood cell count; CBCL, Child Behavior Checklist; CGI, Clinical Global Impression; CI, confidence interval; CR, controlled release; FISH, Family Inventory of Sleep Habits; FR, fast release; FSH, follicle- stimulating hormone; LH, luteinizing hormone; MCV, mean corpuscular volume; PSI, Parental Stress Index; RBS, Repetitive Behavior Scale; SI, Sensory Integration; SS, Spectrum Support; TTM, Thai Traditional Massage. SUPPLEMENT ARTICLE

insomnia in children (not specificto ASD) were identified. Parent Parent Parent Parent Parent Adolescent Respondent The results of the systematic literature review demonstrate that treatment trials are limited in the ASD population. There are 3 categories of treatment: pharmacologic/biologic treatments, behavioral/educational interventions,

culty going to bed and and complementary and alternative fi medicine. Theevidencebasetodateshowslimited

Format evidence for the use of medications to treat insomnia in children who have ASD. The most evidence exists for the use of supplemental melatonin, an indoleamine with sleep-promoting and

ve items that roll into 8 subscales: bedtime resistance, chronobiotic (sleep phase shifting) fi sleep onset delay, sleep duration, sleep anxiety, nightparasomnias, wakings, sleep-disordered breathing, and daytime sleepiness falling asleep); excessive daytime sleepinessbehaviors (includes typically associated with daytime somnolencechildren); awakenings in during the night;wake regularity cycles of (bedtime, wake sleep/ time) and average sleepand duration; snoring maintenance, daytime sleepiness, sleep arousal, anddisordered breathing sleep- routine, and sleep environment sensitivity to the environment; disorientedfacilitators; awakening; and sleep apnea/bruxism asleep, awakening, reinitiating sleep, and wakefulness properties considered a nutritional Forty- Same as the CSHQ (above)Twenty-six items that role into 6 subscales: sleep initiation and Twelve items, including daytime and prebedtime habits, bedtime Parent Five sleep domains: bedtime problems (dif Twenty-eight items role into 5 subscales: going to bed, falling Five types of sleep problems: expressive sleep disturbances; supplement by the US Food and Drug Administration. Several small, ran- domized controlled trials (RCTs) dem- onstrated the efficacy of supplemental melatonin in treating insomnia in children who have ASD,27–29 although larger studies are needed. Melatonin seems to be relatively safe based on these trials and on other series.30 Other pharmacologic interventions Description such as risperidone, secretin, L-carni- tine, niaprazine, mirtazapine, and clo- nidine, as well as multivitamins and c questionnaireassessingsleephygieneinchildren fi iron, have limited evidence supporting their use in treating insomnia in ASD.

medical dimensions in children aged 4 to 10 y autism, developmental delay without autism, anddeveloping children typically 5to15y aged 3 to 10 y The research evidence to date does not Assesses sleep behaviors across a range of behavioral and Assesses the CSHQ (see above) in children aged 2 to 5.5 y with Characterizes sleep disorders over the past 6 mo in childrenaged Autismspeci Assesses sleep behaviors in children aged 5 to 12 y Assesses 5 sleep domains in children aged 5 to 18 y Assesses sleep quality in adolescents aged 11 to 21 y support the efficacy of other supple- ments or vitamins. Behavioral interventions are clearly beneficial for typically developing chil- 39 dren experiencing significant insom- nia.21 However, few treatment trials

23 found that behavioral treatments pro- 37 vide consistent success rates in chil- 38 dren who have ASD, particularly those 40 experiencing sleep-onset insomnia. The 36 Questionnaire systematic review of the literature iden- tified 2 studies examining the efficacy of behavioral treatment of insomnia Sleep Questionnaire Options 31,32 s Sleep Habits Questionnaire in Toddlers and Preschool ’ in children who have ASD. Each of 17 these studies demonstrated statisti- Children (Goodlin-Jones et al, 2008) TABLE 2 BEARS, B = Bedtime problems, E = Excessive Daytime Sleepiness, A = Awakenings During the Night, R = Regularity and Duration of Sleep, S = Snoring. CSHQ (Owens et al, 2000) Children Sleep Disturbance Scale for Children Adolescent Sleep Wake Scale Family Inventory of Sleep Habits Behavioral Evaluation of Disorders of Sleep Scale BEARS cally significant improvements in sleep

PEDIATRICS Volume 130, Supplement 2, November 2012 S119 Downloaded from www.aappublications.org/news by guest on October 2, 2021 posttreatment. Both studies used mul- single study included sleep hygiene in- Results of the Guideline ticomponent treatments, although they structions, use of effective instructions/ Development varied with respect to the specific directions to shape appropriate sleep Based on the feasibility testing, a number components of treatment. However, behavior, and use of the bedtime pass of observations resulted in the devel- they were representative of treatments protocol.23 The studies did not address opment of resources to assist clinicians commonly used in clinical practice as relative efficacy of these individual treat- in the application of the practice pathway. well as supported as effective in the ment components. After reviewing the literature and con- general pediatric population. Both Complementary and alternative medi- ducting pilot testing, the ATN Sleep studies used extinction and positive cine therapies addressed in the litera- Committee developed and refined the reinforcement as treatments. Both ture review include massage therapy insomnia practice pathway and made the studies provided parent training, as and aromatherapy.33–35 The systematic following consensus recommendations: follows: (1) identifying a treatment review found no evidence to support A. General pediatricians, family care goal/treatment target for therapy; (2) these therapies for insomnia in chil- providers, and autism medical spe- discussion of how the sleep problem is dren who have ASD. Neither of the cialists should screen all children maintained by conditioning/learning; graded studies examining the efficacy who have ASD for insomnia. and (3) emphasis on establishing a de- of massage therapy or aromatherapy This screening is best done by asking velopmentally appropriate bedtime for insomnia in children who have ASD a short series of questions targeting and a consistent bedtime routine. Other led to statistically significant improve- insomnia, such as those from the treatment components addressed in a ments in sleep posttreatment.33–35 CSHQ, and asking if the parent consid- ers these a problem. These questions TABLE 3 Questionnaire to Help Identify Underlying Medical Conditions are: (1) child falls asleep within 20 minutes after going to bed; (2) child falls asleep in parent’s or sibling’s bed; (3) child sleeps too little; and (4) child awakens once during the night. These questions were selected on the basis of review of the CSHQ and expert con- sensus. The ATN database was also reviewed (n = 4887), and we found that 81% of parents who reported that their child awakening more than once during the night was a problem also answered affirmatively to the question “Does your child awaken once during the night?” Therefore, to limit the questions asked, we did not in- clude “Does your child awaken more than once during the night?” Asking specific questions is essential because parents may not volunteer concerns about insomnia given their concerns with behavioral issues (although these issues may be secondary to the in- somnia). Identifying significant insom- nia is paramount given its impact on daytime functioning, not only for the child with ASD but also the family. Table 2 lists available questionnaires. B. The evaluation of insomnia should include attention to medical

S120 MALOW et al Downloaded from www.aappublications.org/news by guest on October 2, 2021 SUPPLEMENT ARTICLE

contributors that can affect sleep parents related to going to bed and fall- depending on the comfort level of the (including neurologic conditions and ing asleep. Conversely, given preferences pediatrician. other sleep disorders that contrib- for sameness and routine, children who ute to insomnia). have ASD may adapt well to establish- Behavioral Treatments for Insomnia These contributors should be ad- ment of bedtime routines, especially if The behavioral treatments most com- dressed because their treatment may visual schedules are implemented. monly used to treat insomnia in chil- improve insomnia. Within the ATN, we The ATN has developed an educational dren who have ASD include behavioral have developed a list of questions for toolkit for parents that consists of modification strategies such as extinc- medical contributors, including gas- pamphlets to promote good sleep tion (eg, withdrawal of reinforcement trointestinal disorders, epilepsy, pain, habits; a survey to assess for habits for inappropriate bedtime behaviors) nutritional issues, and other under- that may interfere with sleep; sample and positive reinforcement of adaptive lying sleep disorders responsible for bedtime routines, including a visual sleep behavior. Sleep hygiene instruc- insomnia, including sleep-disodered supports library, tip sheets for imple- tions (eg, appropriate sleep schedules breathing and restless legs symptoms menting the bedtime routine, and and routines) often accompany behav- (Table 3) that pediatricians can in- managing night wakings; and a sleep ioral modification protocols. Behavioral corporate within their review of sys- diary. The toolkit is being tested for interventions are effective in the treat- tems. Psychiatric conditions, such as feasibility in an ongoing research pro- ment of insomnia in typically developing 21 anxiety, depression, and bipolar disor- ject funded by the Health Resources children. However, the evidence base der, should be considered because and Services Administration of parent for effectiveness of such interventions in these may contribute to insomnia. Fi- sleep education at 4 ATN sites and is children who have ASD is limited. The nally, because many medications con- also being used in clinical practice data from the literature review provide tribute to insomnia, a careful review of throughout the network. As with other preliminary support for the use of be- fi medications should be performed. educational/behavioral approaches, havioral modi cation to treat insomnia in children who have ASD. These data C. Educational/behavioral interventions the success of this toolkit depends on were the basis for the development of an are the first line of treatment, after appropriate implementation by par- educational toolkit used to guide behav- excluding medical contributors. How- ents, with the guidance provided by ioral management of insomnia in the ever, if an educational (behavioral) practitioners an essential element for insomnia practice pathway. approach does not seem feasible, many families. Families can often be or the intensity of symptoms has encouraged to implement educational/ Alternative Treatments for Insomnia reached a crisis point, the use of phar- behavioral strategies when presented macologic treatment is considered. with these tools, especially if they re- The most common alternative therapy with a presence in the literature is mas- Educational/behavioral approaches to ceive hands-on instruction in the tools sage therapy.33,35 However, the results do the treatment of insomnia are advo- and are provided with an explanation of not demonstrate consistent, statistically cated as a first-line treatment in typi- why a behavioral approach is recom- significant improvements in sleep. cally developing children.21 In children mended. However, some families may who have ASD, educational/behavioral be in a state of crisis or may not be approaches are also recommended, willing or able to use the behavioral Pharmacologic Treatments for especially because these children may tools. These families may be challenged Insomnia not be capable of expressing adverse by difficult daytime behaviors in their Although medications and supplements effects caused by the medications. The child or by financial concerns. These are often used to treat insomnia experi- core behavioral deficits associated children might require pharmacologic enced by children and adolescents who with ASD may impede the establish- treatment. In addition, practitioners may have ASD, the evidence base for phar- ment of sound bedtime behaviors and not be able to provide sufficient in- macologic treatment is limited. At this routines. These include: (1) difficulty struction in the tools for a family to be time, there are no medications approved with emotional regulation (eg, ability to successful with their implementation. by the US Food and Drug Administration calm self); (2) difficulty transitioning Therefore, there is the option in the for pediatric insomnia. The most evi- from preferred or stimulating activi- practice pathway (Fig 2, Box 5b) of dence exists for the use of melatonin. ties to sleep; and (3) deficits in com- medication or consultation to a sleep D. Clinicians should assure timely munication skills affecting a child’s specialist if the family is unwilling or follow-up to monitor progress and understanding of the expectations of unable to use an educational approach, resolution of insomnia.

PEDIATRICS Volume 130, Supplement 2, November 2012 S121 Downloaded from www.aappublications.org/news by guest on October 2, 2021 Assuring adequate follow-up is crucial including:(1)competingdemandsonthe evaluation/treatment of medical con- when treating children who have ASD pediatric provider in a busy clinical tributors and the implementation of and significant insomnia. Follow-up practice; (2) knowledge level of the pe- educational measures became a paral- should occur within 2 weeks to 1 diatric provider; and (3) when consul- lel process as opposed to a sequential month after beginning treatment. The tation to the sleep specialist occurs, “first–then” approach. provider and family should expect to ensuring communication back to the see some benefits and improvements pediatric provider. DISCUSSION within 4 weeks. Follow-up may be con- In response to these barriers, we de- ducted by telephone or in person. veloped the following resources: (1) We report here on the development of fi Timely follow-up allows for ne-tuning a short set of screening questions for a practice pathway for the evaluation of treatment interventions, support of insomnia as well as a checklist for and management of insomnia in chil- parents, and provision of referrals if medical conditions contributing to in- dren who have ASD. There are several needed. In addition to short-term somnia (Table 3); and (2) a sleep edu- key points of this practice pathway. – follow-up (eg, 1 2 months), at long- cation toolkit, available in hard copy as First, general pediatricians, primary term follow-up (eg, 1-year visit) the well as on the internal ATN Web site care providers, and autism medical steps from the beginning of the prac- (www.autismspeaks.org/atn) that will specialists should screen all children tice pathway should be repeated. facilitate parent teaching. who have ASD for insomnia because parents may not volunteer sleep con- As outlined in the practice pathway, Additional issues were identified re- cerns despite these concerns being treatment of insomnia can be initiated lated to provider comfort level in the contributors to medical comorbidities by the general pediatrician, primary following areas: (1) assessing for and behavioral issues. Second, the care provider, or autism medical spe- medical or sleep contributors them- evaluation of insomnia should in- cialist. Many children will improve with selves rather than referring to a spe- clude attention to medical contributors these initial interventions. Consultation cialist, which led us to modify the with a sleep specialist is indicated if that can affect sleep, including other practice pathway to allow for both medical problems that encompass insomnia is not improving with these options; (2) providing education to initial interventions or when the in- gastrointestinal disorders, epilepsy, families in use of the toolkit, which af- psychiatric comorbidities, medications, somnia is particularly severe, causing fected the length at which follow-up fi and sleep disorders including sleep- signi cant daytime impairment or occurred (eg, a second visit with placing the child at risk for harm while disordered breathing, restless legs a nurse educator might be needed for awake during the night. For those syndrome (unpleasant sensations in the toolkit implementation if the provider children who have ASD and are taking legs associated with an urge to move), was too busy to educate families at the multiple medications for sleep when periodic limb movements of sleep time of the initial clinic visit); and (3) initially assessed by the health care (rhythmic leg kicks during sleep), and treating insomnia with medications on provider, consultation with a sleep parasomnias (undesirable move- their own versus referring to a sleep specialist may be indicated, depending ments or behaviors during sleep, specialist. When a child was referred to on the comfort level of the provider. such as sleepwalking, sleep terrors, or the sleep specialist, ensuring that the Other indications for consultation with confusional arousals). In parallel with sleep specialist communicated back a pediatric sleep specialist may include this screening, the need for therapeu- to the provider regarding recommen- when underlying sleep disorders are tic intervention should be determined. dations was also an issue related to responsible for the sleeplessness We also determined that educational/ applying the practice pathway in our symptoms (including sleep apnea, behavioral interventions are the first field testing, particularly as related to restless legs syndrome, periodic limb line of treatment, after excluding follow-up care. movements of sleep, and unusual night- medical contributors. If an educa- time behaviors [parasomnias] such as We modified the flow of the practice tional (behavioral) approach does not sleepwalking or sleep terrors). pathway in response to feedback dur- seem feasible, or the intensity of ing the field testing. Initially, the prac- symptoms has reached a crisis point, tice pathway prioritized evaluation the use of pharmacologic treat- Results of the Field Testing and treatment of medical contributors ment is considered. Finally, clinicians Results of the pilot phase indicated before implementing educational should assure timely follow-up to challenges in implementing the practice measures, such as the toolkit. However, monitor progress and resolution of pathway due to a number of conflicts, based on the feedback of clinicians, the insomnia.

S122 MALOW et al Downloaded from www.aappublications.org/news by guest on October 2, 2021 SUPPLEMENT ARTICLE

This practice pathway expands the lit- comorbid conditions, parental stres- practices. We would also like to develop erature that currently exists for typi- sors, and prevalent sleep problems. a practice pathway for nonmedical cally developing children related to The systematic review of the available health professionals who are likely to screening and management.5,7–9 The treatment literature allowed for the provide behavioral interventions, in- rationale for developing a practice recognition that evidence-based stan- cluding psychologists. pathway that uniquely addresses this dards for the behavioral, pharmaco- Strengths of the study include the gath- population is because children who logic, and other treatments of insomnia ering of the following groups: experts in have ASD, and their families, have in ASD are not yet available. Thus, much sleep medicine from a variety of dis- unique needs. For example, medical, of these guidelines reflect expert ciplines, including neurology, psychiatry, neurologic, and psychiatric comorbid- opinion given the absence of data. Ad- pulmonary medicine, and psychology; ities are common in children who have ditional studies are needed to establish engaged pediatricians specializing ASD, as is the use of medications that the efficacy and safety of supplemental in ASD; and parents of children who influence sleep. In addition, parents of melatonin, as well as other pharma- have ASD. Weaknesses include limited children who have ASD, struggling with cologic agents, in large RCTs. Similar evidence-basedstudiesonwhichtobase the stressors related to their child’s studies are needed to address the ef- the practice pathway, making it neces- disability and the often accompanying ficacy of parent-based sleep educa- sary to rely on expert opinion. behavioral challenges, may not volun- tional programs to address insomnia, teer sleep to be of concern. In turn, as well as the combination of these CONCLUSIONS pediatric providers may not ask about educational programs with pharma- The practice pathway regarding the sleep due to competing medical and cologic strategies. Finally, the role identification of insomnia in children behavioral issues. Furthermore, sleep of nonpharmacologic methods (apart who have ASD requires future field problems are more common in chil- from educational therapies) warrants testing in clinical settings but repre- dren who have ASD than in children study as well. As additional research sents a starting point to managing in- 2,3 of typical development, and their studies are performed, the clinical somnia in a growing population of treatment may impact favorably on pathwaywilllikelyrequiremodification. children with the most common daytime behavior and family function- However, it is expected that the over- neurodevelopmental disability. ing. Given these factors, we do recog- arching approach to insomnia in the nize that children who have other child who has ASD will not change. Al- ACKNOWLEDGMENT disorders of neurodevelopment could though the practice pathway was Thevaluableassistanceofthemembers also benefit from this practice pathway, piloted at 4 ATN sites, the next steps of the ATN Sleep Committee in re- as they share common features with involve the wide dissemination of viewing this document is gratefully children who have ASD, including the practice pathway into pediatric acknowledged.

REFERENCES

1. American Psychiatric Association. Di- 4. American Academy of Sleep Medicine. In- 9. Zuckerman B, Stevenson J, Bailey V. Sleep agnostic and Statistical Manual of Mental ternational Classification of Sleep Disorders. problems in early childhood: continuities, Disorders, Revised. 4th ed. Washington, Diagnostic and Coding Manual.2nded. predictive factors, and behavioral corre- DC: American Psychiatric Association; Westchester, IL: American Academy of Sleep lates. Pediatrics. 1987;80(5):664–671 2000 Medicine; 2005 10. Wiggs L, Stores G. Severe sleep disturbance 2. Couturier JL, Speechley KN, Steele M, Norman 5. Armstrong KL, Quinn RA, Dadds MR. The and daytime challenging behaviour in R, Stringer B, Nicolson R. Parental perception sleep patterns of normal children. Med J children with severe learning disabilities. J ofsleepproblemsinchildrenofnormalintel- Aust. 1994;161(3):202–206 Intellect Disabil Res. 1996;40(pt 6):518–528 ligence with pervasive developmental dis- 6. Johnson KP, Malow BA. Assessment and 11. Wiggs L, Stores G. Behavioural treatment for orders: prevalence, severity, and pattern. JAm pharmacologic treatment of sleep distur- sleepproblemsinchildrenwithsevere Acad Child Adolesc Psychiatry. 2005;44(8): bance in autism. Child Adolesc Psychiatr learning disabilities and challenging daytime 815–822 Clin N Am. 2008;17(4):773–785, viii behaviour: effect on daytime behaviour. 3. Krakowiak P, Goodlin-Jones B, Hertz- 7. Kataria S, Swanson MS, Trevathan GE. Per- J Child Psychol Psychiatry. 1999;40(4):627–635 Picciotto I, Croen LA, Hansen RL. Sleep sistence of sleep disturbances in preschool 12. Meltzer LJ, Johnson C, Crosette J, Ramos M, problems in children with autism spec- children. J Pediatr. 1987;110(4):642–646 Mindell JA. Prevalence of diagnosed sleep trum disorders, developmental delays, and 8. Pollock JI. Night-waking at five years of age: disorders in pediatric primary care practices. typical development: a population-based predictors and prognosis. J Child Psychol Pediatrics. 2010;125(6). Available at: www. study. J Sleep Res. 2008;17(2):197–206 Psychiatry. 1994;35(4):699–708 pediatrics.org/cgi/content/full/125/6/e1410

PEDIATRICS Volume 130, Supplement 2, November 2012 S123 Downloaded from www.aappublications.org/news by guest on October 2, 2021 13. Meissner HH, Riemer A, Santiago SM, Stein autistic spectrum disorders and sleep between reported sleep quality and sleep M, Goldman MD, Williams AJ. Failure of problems. Child Care Health Dev. 2006;32 hygieneinItalianandAmericanadolescents. physician documentation of sleep com- (5):585–589 Pediatrics. 2005;115(suppl 1):257–265 plaints in hospitalized patients. West J Med. 28. Wirojanan J, Jacquemont S, Diaz R, et al. 41. Aman MG, Arnold LE, McDougle CJ, et al. 1998;169(3):146–149 The efficacy of melatonin for sleep prob- Acute and long-term safety and tolerability 14. Owens JA. The practice of pediatric sleep lems in children with autism, fragile X of risperidone in children with autism. medicine: results of a community survey. syndrome, or autism and fragile X syn- J Child Adolesc Psychopharmacol. 2005;15 Pediatrics. 2001;108(3). Available at: www. drome. J Clin Sleep Med. 2009;5(2):145–150 (6):869–884 pediatrics.org/cgi/content/full/108/3/E51 29. Wasdell MB, Jan JE, Bomben MM, et al. A 42. Honomichl RD, Goodlin-Jones BL, Burnham 15. Blunden S, Lushington K, Lorenzen B, Ooi T, randomized, placebo-controlled trial of MM, Hansen RL, Anders TF. Secretin and Fung F, Kennedy D. Are sleep problems controlled release melatonin treatment of sleep in children with autism. Child Psy- under-recognised in general practice? Arch delayed sleep phase syndrome and im- chiatry Hum Dev. 2002;33(2):107–123 Dis Child. 2004;89(8):708–712 paired sleep maintenance in children with 43. Ellaway CJ, Peat J, Williams K, Leonard H, 16. Schreck KA, Richdale AL. Knowledge of neurodevelopmental disabilities. J Pineal Christodoulou J. Medium-term open label childhood sleep: a possible variable in un- Res. 2008;44(1):57–64 trial of L-carnitine in Rett syndrome. Brain der or misdiagnosis of childhood sleep 30. Andersen IM, Kaczmarska J, McGrew SG, Dev. 2001;23(suppl 1):S85–S89 problems. J Sleep Res. 2011;20(4):589–597 Malow BA. Melatonin for insomnia in chil- 44. Posey DJ, Guenin KD, Kohn AE, Swiezy NB, 17. Owens JA, Dalzell V. Use of the ‘BEARS’ sleep dren with autism spectrum disorders. McDougle CJ. A naturalistic open-label study screening tool in a pediatric residents’ J Child Neurol. 2008;23(5):482–485 of mirtazapine in autistic and other perva- continuity clinic: a pilot study. Sleep Med. 31. Reed HE, McGrew SG, Artibee K, et al. Parent- sive developmental disorders. J Child Ado- 2005;6(1):63–69 based sleep education workshops in autism. lesc Psychopharmacol. 2001;11(3):267–277 18. Mindell JA, Kuhn B, Lewin DS, Meltzer LJ, J Child Neurol. 2009;24(8):936–945 45. Rossi PG, Posar A, Parmeggiani A, Pipitone Sadeh A; American Academy of Sleep Medi- 32. Weiskop S, Richdale A, Matthews J. Behav- E, D’Agata M. Niaprazine in the treatment of cine. Behavioral treatment of bedtime prob- ioural treatment to reduce sleep problems in autistic disorder. J Child Neurol. 1999;14(8): lems and night wakings in infants and young children with autism or fragile X syndrome. 547–550 children. Sleep. 2006;29(10):1263–1276 Dev Med Child Neurol. 2005;47(2):94–104 46. Ming X, Gordon E, Kang N, Wagner GC. Use of 19. Mindell JA. Empirically supported treat- 33. Piravej K, Tangtrongchitr P, Chandarasiri P, clonidine in children with autism spectrum ments in pediatric psychology: bedtime Paothong L, Sukprasong S. Effects of Thai disorders. Brain Dev. 2008;30(7):454–460 refusal and night wakings in young chil- traditional massage on autistic children’s 47. Adams JB, Holloway C. Pilot study of – dren. J Pediatr Psychol. 1999;24(6):465 481 behavior. J Altern Complement Med. 2009; a moderate dose multivitamin/mineral 20. Kuhn BR, Elliott AJ. Treatment efficacy in 15(12):1355–1361 supplement for children with autistic behavioral pediatric sleep medicine. J 34. Williams TI. Evaluating effects of aroma- spectrum disorder. J Altern Complement Psychosom Res. 2003;54(6):587–597 therapy massage on sleep in children with Med. 2004;10(6):1033–1039 21. Morgenthaler TI, Owens J, Alessi C, et al; autism: a pilot study. Evid Based Comple- 48. Dosman CF, Brian JA, Drmic IE, et al. Chil- American Academy of Sleep Medicine. ment Alternat Med. 2006;3(3):373–377 dren with autism: effect of iron supple- Practice parameters for behavioral treat- 35. Escalona A, Field T, Singer-Strunck R, Cullen mentation on sleep and ferritin. Pediatr ment of bedtime problems and night wak- C, Hartshorn K. Brief report: improvements Neurol. 2007;36(3):152–158 ings in infants and young children. Sleep. in the behavior of children with autism 49. Wright B, Sims D, Smart S, et al. Melatonin – 2006;29(10):1277 1281 following massage therapy. J Autism Dev versus placebo in children with autism 22. Reynolds AM, Malow BA. Sleep and autism Disord. 2001;31(5):513–516 spectrum conditions and severe sleep spectrum disorders. Pediatr Clin North Am. 36. Owens JA, Spirito A, McGuinn M. The problems not amenable to behaviour 2011;58(3):685–698 Children’s Sleep Habits Questionnaire management strategies: a randomised 23. Goodlin-Jones BL, Sitnick SL, Tang K, Liu J, (CSHQ): psychometric properties of a sur- controlled crossover trial. J Autism Dev Anders TF. The Children’s Sleep Habits Ques- vey instrument for school-aged children. Disord. 2011;41(2):175–184 tionnaire in toddlers and preschool children. Sleep. 2000;23(8):1043–1051 50. Paavonen EJ, Nieminen-von Wendt T, Vanhala J Dev Behav Pediatr. 2008;29(2):82–88 37. Bruni O, Ottaviano S, Guidetti V, et al. The R, Aronen ET, von Wendt L. Effectiveness of 24. Guyatt GH, Oxman AD, Vist GE, et al; GRADE Sleep Disturbance Scale for Children melatonin in the treatment of sleep dis- Working Group. GRADE: an emerging con- (SDSC). Construction and validation of an turbancesinchildrenwithAspergerdisor- sensus on rating quality of evidence and instrument to evaluate sleep disturbances der. J Child Adolesc Psychopharmacol. 2003; strength of recommendations. BMJ. 2008; in childhood and adolescence. J Sleep Res. 13(1):83–95 336(7650):924–926 1996;5(4):251–261 51. Giannotti F, Cortesi F, Cerquiglini A, 25. Owens JA, Moturi S. Pharmacologic treat- 38. Malow BA, Crowe C, Henderson L, et al. A Bernabei P. An open-label study of controlled- ment of pediatric insomnia. Child Adolesc sleep habits questionnaire for children release melatonin in treatment of sleep Psychiatr Clin N Am. 2009;18(4):1001–1016 with autism spectrum disorders. J Child disorders in children with autism. J Autism 26. Mindell JA, Emslie G, Blumer J, et al. Phar- Neurol. 2009;24(1):19–24 Dev Disord. 2006;36(6):741–752 macologic management of insomnia in chil- 39. Schreck KA, Mulick JA, Rojahn J. Devel- 52. Malow B, Adkins KW, McGrew SG, et al. Mel- dren and adolescents: consensus statement. opment of the behavioral evaluation of dis- atonin for sleep in children with autism: Pediatrics. 2006;117(6). Available at: www. orders of sleep scale. JChildFamStud. 2003; a controlled trial examining dose, tolerability, pediatrics.org/cgi/content/full/117/6/e1223 12(3):349–359 doi:10.1023/A:1023995912428 and outcomes [published correction appears 27. Garstang J, Wallis M. Randomized con- 40. LeBourgeois MK, Giannotti F, Cortesi F, in JAutismDevDisord. 2012;42(8):1738]. trolled trial of melatonin for children with WolfsonAR,HarshJ.Therelationship JAutismDevDisord. 2012;42(8):1729–1737

S124 MALOW et al Downloaded from www.aappublications.org/news by guest on October 2, 2021 A Practice Pathway for the Identification, Evaluation, and Management of Insomnia in Children and Adolescents With Autism Spectrum Disorders Beth A. Malow, Kelly Byars, Kyle Johnson, Shelly Weiss, Pilar Bernal, Suzanne E. Goldman, Rebecca Panzer, Daniel L. Coury and Dan G. Glaze Pediatrics 2012;130;S106 DOI: 10.1542/peds.2012-0900I

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/130/Supplement_2/S106 References This article cites 49 articles, 6 of which you can access for free at: http://pediatrics.aappublications.org/content/130/Supplement_2/S106 #BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Developmental/Behavioral Pediatrics http://www.aappublications.org/cgi/collection/development:behavior al_issues_sub Autism/ASD http://www.aappublications.org/cgi/collection/autism:asd_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on October 2, 2021 A Practice Pathway for the Identification, Evaluation, and Management of Insomnia in Children and Adolescents With Autism Spectrum Disorders Beth A. Malow, Kelly Byars, Kyle Johnson, Shelly Weiss, Pilar Bernal, Suzanne E. Goldman, Rebecca Panzer, Daniel L. Coury and Dan G. Glaze Pediatrics 2012;130;S106 DOI: 10.1542/peds.2012-0900I

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/130/Supplement_2/S106

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2012 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

Downloaded from www.aappublications.org/news by guest on October 2, 2021