Current Pharmacological Treatment for Sleep Disorders in Children and Adolescents with Autism Spectrum Disorder


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DOI:

https://doi.org/10.58600/eurjther1978

Keywords:

Autism spectrum disorder, sleep, Sleep Initiation and Maintenance Disorders, Pharmacological Treatment, melatonin

Abstract

Sleep disorders are very common in children and adolescents with Autism Spectrum Disorder (ASD) and can negatively impact their lives, mental health, developmental processes, families' lives, and emotional well-being. It is essential to determine the specific sleep disorder and its underlying cause in treatment planning. Currently, nonpharmacological and pharmacological interventions are the main treatments for improving sleep disorders in children and adolescents with ASD. If nonpharmacological strategies are unsuccessful or difficult to implement, medications should be considered and used in conjunction with them. Melatonin, behavioral interventions, and parent education are the most effective treatments to improve sleep, relative to other pharmacological treatments. Medications used to treat sleep disorders in these children are used off-label. Melatonin appearing to be safe and effective may be an evidence-based and efficacious first-line treatment for treating insomnia symptoms in children and adolescents with ASD. Antipsychotics (e.g.low dose quetiapine), antidepressants with strong sedative effects such as trazodone and mirtazapine, antihistamines (e.g.diphenhydramine, niaprazine), alpha-adrenergic drugs (e.g. clonidine), benzodiazepines (e.g.clonazepam) and other hypnotic drugs, anticonvulsants (e.g. gabapentin), Alzheimer's drugs (e..g donepezil), superoxide and iron treatment are other drugs used in pharmacological treatment. Depending on the type of sleep disorders and the presence of comorbidities, the most effective pharmacological treatment should be selected on a case-by-case basis.

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References

Maenner MJ, Warren Z, Williams AR, Amoakohene E, Bakian AV, Bilder DA, Durkin MS, Fitzgerald RT, Furnier SM, Hughes MM (2023) Prevalence and characteristics of autism spectrum disorder among children aged 8 years—Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2020. MMWR Surveil Summ. 72(2): 1–14. http://dx.doi.org/10.15585/mmwr.ss7202a1

Karthikeyan R, Cardinali DP, Shakunthala V, Spence DW, Brown GM, Pandi-Perumal SR (2020) Understanding the role of sleep and ıts disturbances in autism spectrum disorder. Int J Neurosci. 130 (10): 1033-1046. https://doi.org/10.1080/00207454.2019.1711377

Dahl RE (2007) Sleep and the developing brain. Sleep. 30(9):1079-1080. https://doi.org/10.1093/sleep/30.9.1079

Burman D, Ramanujam K, Manzar D, Chattu VK, Spence DW, Zaki NF, Jahrami H, Pandi-Perumal SR (2023) Sleep and autism spectrum disorder: a comprehensive review of diagnosis, markers, ınterventions, and treatments. Sleep Vigil. 7: 9-22. http://dx.doi.org/10.1007/s41782-022-00222-3

Rana M, Kothare S, DeBassio W (2021) The assessment and treatment of sleep abnormalities in children and adolescents with autism spectrum disorder: a review. J Can Acad Child Adolesc Psychiatry. 30(1):25-35.

Chen H, Yang T, Chen J, Chen L, Dai Y, Zhang J, Li L, Jia F, Wu L, Hao Y (2021) Sleep problems in children with autism spectrum disorder: a multicenter survey. BMC psychiatry. 21 (1):406. http://dx.doi.org/10.1186/s12888-021-03405-w

Mazurek MO, Sohl K (2016) Sleep and behavioral problems in children with autism spectrum disorder. J Autism Dev Disord. 46 (6): 1906-1915. http://dx.doi.org/10.1007/s10803-016-2723-7

Wiggs L, Stores G (2004) Sleep patterns and sleep disorders in children with autistic spectrum disorders: insights using parent report and actigraphy. Dev Med Child Neurol. 46: 372-380. http://dx.doi.org/10.1017/s0012162204000611

Inthikoot N, Chonchaiya W (2021) Sleep problems in children with autism spectrum disorder and typical development. Pediatr Int. 63: 649-657. http://dx.doi.org/10.1111/ped.14496

Cortese S, Wang F, Angriman M, Masi G, Bruni O (2020) Sleep disorders in children and adolescents with autism spectrum disorder: diagnosis, epidemiology, and management. CNS drugs. 34: 415-423. http://dx.doi.org/10.1007/s40263-020-00710-y

Goldman SE, Richdale AL, Clemons T, Malow BA (2012) Parental sleep concerns in autism spectrum disorders: variations from childhood to adolescence. J Autism Dev Disord.42: 531-538. http://dx.doi.org/10.1007/s10803-011-1270-5

Hollway JA, Aman MG, Butter E (2013) Correlates and risk markers for sleep disturbance in participants of the autism treatment network. J Autism Dev Disord. 43: 2830-2843. http://dx.doi.org/10.1007/s10803-013-1830-y

Hodge D, Carollo TM, Lewin M, Hoffman CD, Sweeney DP (2014) Sleep patterns in children with and without autism spectrum disorders: developmental comparisons. Res Dev Disabil. 35: 1631-1638 http://dx.doi.org/10.1016/j.ridd.2014.03.037

Taylor MA, Schreck KA, Mulick JA (2012) Sleep disruption as a correlate to cognitive and adaptive behavior problems in autism spectrum disorders. Res Dev Disabil. 33: 1408-1417. http://dx.doi.org/10.1016/j.ridd.2012.03.013

Martin CA, Papadopoulos N, Chellew T, Rinehart NJ, Sciberras E (2019) Associations between parenting stress, parent mental health and child sleep problems for children with ADHD and ASD: Systematic review. Res Dev Disabil. 93: 103463. http://dx.doi.org/10.1016/j.ridd.2019.103463

Sikora DM, Johnson K, Clemons T, Katz T (2012) The relationship between sleep problems and daytime behavior in children of different ages with autism spectrum disorders. Pediatrics. 130: 83-90. http://dx.doi.org/10.1542/peds.2012-0900f

Seo WS (2021) An update on the cause and treatment of sleep disturbance in children and adolescents with autism spectrum disorder. Yeungnam Univ J Med. 38: 275-281. http://dx.doi.org/10.12701/yujm.2021.01410

Recommendations. Autism spectrum disorder in under 19s: support and management | Guidance | NICE. https://www.nice.org.uk/guidance/cg170/chapter/1-Recommendations. Last updated: 14 June 2021 Accessed

Buckley AW, Hirtz D, Oskoui M, Armstrong MJ, Batra A, Bridgemohan C, Coury D, Dawson G, Donley D, Findling RL (2020) Practice guideline: Treatment for insomnia and disrupted sleep behavior in children and adolescents with autism spectrum disorder: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 94: 392-404. http://dx.doi.org/10.1212/wnl.0000000000009033

Malow BA, Katz T, Reynolds AM, Shui A, Carno M, Connolly HV, Coury D, Bennett AE (2016) Sleep difficulties and medications in children with autism spectrum disorders: a registry study. Pediatrics. 137: 98-104. http://dx.doi.org/10.1542/peds.2015-2851h

Bruni O, Angriman M, Calisti F, Comandini A, Esposito G, Cortese S, Ferri R (2018) Practitioner review: treatment of chronic insomnia in children and adolescents with neurodevelopmental disabilities. J Child Psychol Psychiatry. 59: 489-508. http://dx.doi.org/10.1111/jcpp.12812

Schroder CM, Banaschewski T, Fuentes J, Hill CM, Hvolby A, Posserud M-B, Bruni O (2021) Pediatric prolonged-release melatonin for insomnia in children and adolescents with autism spectrum disorders. Expert Opin Pharmacother. 22: 2445-2454. http://dx.doi.org/10.1080/14656566.2021.1959549

Pandi-Perumal SR, Srinivasan V, Spence DW, Cardinali DP (2007) Role of the melatonin system in the control of sleep: therapeutic implications. CNS drugs. 21: 995-1018. http://dx.doi.org/10.2165/00023210-200721120-00004

Yousaf F, Seet E, Venkatraghavan L, Abrishami A, Chung F, Warner DS (2010) Efficacy and safety of melatonin as an anxiolytic and analgesic in the perioperative period: a qualitative systematic review of randomized trials. Anesthesiology. 113: 968-976. http://dx.doi.org/10.1097/aln.0b013e3181e7d626

Hayashi M, Mishima K, Fukumizu M, Takahashi H, Ishikawa Y, Hamada I, Sugioka H, Yotsuya O, Yamashita Y (2022) Melatonin treatment and adequate sleep hygiene interventions in children with autism spectrum disorder: a randomized controlled trial. J Autism Dev Disord. 52(6):2784-2793. http://dx.doi.org/10.1007/s10803-021-05139-w

Gringras P, Nir T, Breddy J, Frydman-Marom A, Findling RL (2017) Efficacy and safety of pediatric prolonged-release melatonin for insomnia in children with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 56(11):948-957.e4. http://dx.doi.org/10.1016/j.jaac.2017.09.414

Xiong M, Li F, Liu Z, Xie X, Shen H, Li W, Wei L, He R (2023) Efficacy of Melatonin for Insomnia in Children with Autism Spectrum Disorder: A Meta-analysis. Neuropediatrics. 54: 167-173. http://dx.doi.org/10.1055/s-0043-1761437

Maras A, Schroder CM, Malow BA, Findling RL, Breddy J, Nir T, Shahmoon S, Zisapel N, Gringras P (2018) Long-term efficacy and safety of pediatric prolonged-release melatonin for insomnia in children with autism spectrum disorder J Child Adolesc Psychopharmacol. 28: 699-710. http://dx.doi.org/10.1089/cap.2018.0020

Rossignol DA, Frye RE (2011) Melatonin in autism spectrum disorders: a systematic review and meta‐analysis. Dev Med Child Neurol. 53(9):783-792. http://dx.doi.org/10.1111/j.1469-8749.2011.03980.x

Malow B, Adkins KW, McGrew SG, Wang L, Goldman SE, Fawkes D, Burnette C (2012) Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes. J Autism Dev Disord. 42: 1729-1737. http://dx.doi.org/10.1007/s10803-011-1418-3

Andersen IM, Kaczmarska J, McGrew SG, Malow BA (2008) Melatonin for insomnia in children with autism spectrum disorders. J Child Neurol. 23(5):482-485. http://dx.doi.org/10.1177/0883073807309783

Gringras P, Gamble C, Jones A, Wiggs L, Williamson P, Sutcliffe A, Montgomery P, Whitehouse W, Choonara I, Allport T (2012) Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial. BMJ. 5:345:e6664. http://dx.doi.org/10.1136/bmj.e6664

Boafo A, Greenham S, Alenezi S, Robillard R, Pajer K, Tavakoli P, De Koninck J (2019) Could long-term administration of melatonin to prepubertal children affect timing of puberty? A clinician’s perspective. Nat Sci Sleep. 31(11):1-10. http://dx.doi.org/10.2147/nss.s181365

Zisapel N (2022) Assessing the potential for drug interactions and long term safety of melatonin for the treatment of insomnia in children with autism spectrum disorder. Expert Review of Clinical Pharmacology Expert Rev Clin Pharmacol. 15 (2): 175-185. http://dx.doi.org/10.1080/17512433.2022.2053520

Waldhauser F, Waldhauser M, Lieberman HR, Deng M-H, Lynch HJ, Wurtman RJ (1984) Bioavailability of oral melatonin in humans. Neuroendocrinology. 39 (4): 307-313. http://dx.doi.org/10.1159/000123997

Bruni O, Alonso-Alconada D, Besag F, Biran V, Braam W, Cortese S, Moavero R, Parisi P, Smits M, Van der Heijden K (2015) Current role of melatonin in pediatric neurology: clinical recommendations. Eur J Paediatr Neurol. 19 (2): 122-133. http://dx.doi.org/10.1016/j.ejpn.2014.12.007

Ballester P, Martínez MJ, Inda M-d-M, Javaloyes A, Richdale AL, Muriel J, Belda C, Toral N, Morales D, Fernández E (2019) Evaluation of agomelatine for the treatment of sleep problems in adults with autism spectrum disorder and co-morbid intellectual disability. J Psychopharmacol. 33(11): 1395-1406. http://dx.doi.org/10.1177/0269881119864968

Kawabe K, Horiuchi F, Oka Y, Ueno S-i (2014) The melatonin receptor agonist ramelteon effectively treats insomnia and behavioral symptoms in autistic disorder. Case Rep Psychiatry. 2014:561071. http://dx.doi.org/10.1155/2014/561071

Aman MG, Arnold M, L Eugene, McDougle CJ, Vitiello B, Scahill L, Davies M, McCracken JT, Tierney E, Nash PL, Posey DJ (2005) Acute and long-term safety and tolerability of risperidone in children with autism J Child Adolesc Psychopharmacol. 15 (6):869-884. http://dx.doi.org/10.1089/cap.2005.15.869

Kent JM, Hough D, Singh J, Karcher K, Pandina G (2013) An open-label extension study of the safety and efficacy of risperidone in children and adolescents with autistic disorder. J Child Adolesc Psychopharmacol. 23 (10): 676-686. http://dx.doi.org/10.1089/cap.2012.0058

Golubchik P, Sever J, Weizman A (2011) Low-dose quetiapine for adolescents with autistic spectrum disorder and aggressive behavior: open-label trial. Clin Neuropharmacol. 34 (6): 216-219. http://dx.doi.org/10.1097/wnf.0b013e31823349ac

Relia S, Ekambaram V (2018) Pharmacological approach to sleep disturbances in autism spectrum disorders with psychiatric comorbidities: a literature review. Med Sci (Basel). 6 (4): 95. http://dx.doi.org/10.3390/medsci6040095

Posey DJ, Guenin KD, Kohn AE, Swiezy NB, McDougle CJ (2001) A naturalistic open-label study of mirtazapine in autistic and other pervasive developmental disorders. J Child Adolesc Psychopharmacol. 11(6): 267-277. http://dx.doi.org/10.1089/10445460152595586

Parker RA, Hartman EE (2002) An 8-year-old boy with autism, 1 year later. JAMA. 287 (4): 504. http://dx.doi.org/10.1001/jama.287.4.504

Wichniak A, Wierzbicka A, Jernajczyk W (2012) Sleep and antidepressant treatment. Curr Pharm Des. 18 (36): 5802-5817. http://dx.doi.org/10.2174/138161212803523608

Russo RM, Gururaj VJ, Allen JE (1976) The effectiveness of diphenhydramine HCI in pediatric sleep disorders. J Clin Pharmacol. 16 (5-6): 284-288. http://dx.doi.org/10.1002/j.1552-4604.1976.tb02406.x

France KG, Blampied NM, Wilkinson P (1999) A multiple-baseline, double-blind evaluation of the effects of trimeprazine tartrate on infant sleep disturbance Exp Clin Psychopharmacol. 7(4):502-513. http://dx.doi.org/10.1037/1064-1297.7.4.502

Rossi PG, Posar A, Parmeggiani A (1999) Niaprazine in the treatment of autistic disorder. J Child Neurol. 14 (8): 547-550. http://dx.doi.org/10.1177/088307389901400814

Ingrassia A, Turk J (2005) The use of clonidine for severe and intractable sleep problems in children with neurodevelopmental disorders: a case series. Eur Child Adolesc Psychiatry. 14 (1): 34-40. http://dx.doi.org/10.1007/s00787-005-0424-4

Ming X, Gordon E, Kang N, Wagner GC (2008) Use of clonidine in children with autism spectrum disorders. Brain Dev. 30 (7): 454-460. http://dx.doi.org/10.1016/j.braindev.2007.12.007

Fiks AG, Mayne SL, Song L, Steffes J, Liu W, McCarn B, Margolis B, Grimes A, Gotlieb E, Localio R (2015) Changing patterns of alpha agonist medication use in children and adolescents 2009–2011. J Child Adolesc Psychopharmacol. 25 (4): 362-367. http://dx.doi.org/10.1089/cap.2014.0122

Politte LC, Scahill L, Figueroa J, McCracken JT, King B, McDougle CJ (2018) A randomized, placebo-controlled trial of extended-release guanfacine in children with autism spectrum disorder and ADHD symptoms: an analysis of secondary outcome measures. Neuropsychopharmacology. 43 (8): 1772-1778. http://dx.doi.org/10.1038/s41386-018-0039-3

Griffin CE, Kaye AM, Bueno FR, Kaye AD (2013) Benzodiazepine pharmacology and central nervous system–mediated effects. Ochsner J. 13 (2): 214-223.

Thirumalai SS, Shubin RA, Robinson R (2002) Rapid eye movement sleep behavior disorder in children with autism. J Child Neurol. 17 (3): 173-178. http://dx.doi.org/10.1177/088307380201700304

Lloyd R, Tippmann-Peikert M, Slocumb N, Kotagal S (2012) Characteristics of REM sleep behavior disorder in childhood. J Clin Sleep Med. 8 (2): 127-131. http://dx.doi.org/10.5664/jcsm.1760

Olson L (2008) Hypnotic hazards: adverse effects of zolpidem and other z-drugs. Aust Prescr. 31:146–9. http://dx.doi.org/10.18773/austprescr.2008.084

Robinson AA, Malow BA (2013) Gabapentin shows promise in treating refractory insomnia in children. J Child Neurol. 28 (2): 1618-1621. http://dx.doi.org/10.1177/0883073812463069

Buckley AW, Sassower K, Rodriguez AJ, Jennison K, Wingert K, Buckley J, Thurm A, Sato S, Swedo S (2011) An open label trial of donepezil for enhancement of rapid eye movement sleep in young children with autism spectrum disorders. J Child Adolesc Psychopharmacol. 21 (4): 353-357. http://dx.doi.org/10.1089/cap.2010.0121

Kawabe K, Horiuchi F, Ochi M, Nishimoto K, Ueno S-I, Oka Y (2017) Suvorexant for the treatment of insomnia in adolescents. J Child Adolesc Psychopharmacol. 27 (9): 792-795. http://dx.doi.org/10.1089/cap.2016.0206

Besterman AD, Jeste SS (2023) Dual orexin receptor antagonists for insomnia in youth with neurodevelopmental disorders: a case series and review. Eur Child Adolesc Psychiatry. 32(3): 527-531. http://dx.doi.org/10.1007/s00787-021-01883-7

Dosman CF, Brian JA, Drmic IE, Senthilselvan A, Harford MM, Smith RW, Sharieff W, Zlotkin SH, Moldofsky H, Roberts SW (2007) Children with autism: effect of iron supplementation on sleep and ferritin. Pediatr Neurol. 36 (3): 152-158. http://dx.doi.org/10.1016/j.pediatrneurol.2006.11.004

Youssef J, Singh K, Huntington N, Becker R, Kothare SV (2013) Relationship of serum ferritin levels to sleep fragmentation and periodic limb movements of sleep on polysomnography in autism spectrum disorders. Pediatr Neurol. 49: 274-278. http://dx.doi.org/10.1016/j.pediatrneurol.2013.06.012

Trotti L, Bhadriraju S, Becker L (2012) Iron for restless legs syndrome. Cochrane Database Syst Rev. 5(5):CD007834. http://dx.doi.org/10.1002/14651858.cd007834.pub2

Daftary AS, Kotagal S (2010) Treatment of childhood obstructive sleep apnea. Curr Treat Options Neurol. 12 (5): 369-378. http://dx.doi.org/10.1007/s11940-010-0084-7

Kheirandish L, Goldbart AD, Gozal D (2006) Intranasal steroids and oral leukotriene modifier therapy in residual sleep-disordered breathing after tonsillectomy and adenoidectomy in children. Pediatrics. 117: e61-e66. http://dx.doi.org/10.1542/peds.2005-0795

Kotagal S (2012) Treatment of dyssomnias and parasomnias in childhood. Curr Treat Options Neurol. 14 (6): 630-649. http://dx.doi.org/10.1007/s11940-012-0199-0

Kanney ML, Durmer JS, Trotti LM, Leu R (2020) Rethinking bedtime resistance in children with autism: is restless legs syndrome to blame? J Clin Sleep Med. 16 (12): 2029-2035. http://dx.doi.org/10.5664/jcsm.8756

Leung AK, Leung AA, Wong AH, Hon KL (2020) Sleep terrors: an updated review. Curr Pediatr Rev. 16 (3): 176-182. http://dx.doi.org/10.2174/1573396315666191014152136

Published

2024-02-12

How to Cite

Altun, H., & Cömertoğlu Arslan, S. (2024). Current Pharmacological Treatment for Sleep Disorders in Children and Adolescents with Autism Spectrum Disorder. European Journal of Therapeutics. https://doi.org/10.58600/eurjther1978

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