Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder

The role of melatonin has been extensively investigated in pathophysiological conditions, including autism spectrum disorder (ASD). Reduced melatonin secretion has been reported in ASD and led to many clinical trials using immediate-release and prolonged-release oral formulations of melatonin. However, melatonin’s effects in ASD and the choice of formulation type require further study. Therapeutic benefits of melatonin on sleep disorders in ASD were observed, notably on sleep latency and sleep quality. Importantly, melatonin may also have a role in improving autistic behavioral impairments. The objective of this article is to review factors influencing treatment response and possible side effects following melatonin administration. It appears that the effects of exposure to exogenous melatonin are dependent on age, sex, route and time of administration, formulation type, dose, and association with several substances (such as tobacco or contraceptive pills). In addition, no major melatonin-related adverse effect was described in typical development and ASD. In conclusion, melatonin represents currently a well-validated and tolerated treatment for sleep disorders in children and adolescents with ASD. A more thorough consideration of factors influencing melatonin pharmacokinetics could illuminate the best use of melatonin in this population. Future studies are required in ASD to explore further dose-effect relationships of melatonin on sleep problems and autistic behavioral impairments.

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Efficacy and Safety of Melatonin Treatment in Children with Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder—A Review of the Literature

Brain Sciences ◽

10.3390/brainsci10040219 ◽

2020 ◽

Vol 10 (4) ◽

pp. 219

Author(s):

Beata Rzepka-Migut ◽

Justyna Paprocka

Keyword(s):

Autism Spectrum Disorder ◽

Attention Deficit Hyperactivity Disorder ◽

Sleep Disorders ◽

Attention Deficit ◽

Sleep Problems ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Melatonin Treatment ◽

Hyperactivity Disorder ◽

Wide Range

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders with disturbed melatonin secretion profile and sleep problems. The growing incidence of ASD and ADHD inspires scientists to research the underlying causes of these conditions. The authors focused on two fundamental aspects, the first one being the presentation of the role of melatonin in ASD and ADHD and the second of the influence of melatonin treatment on sleep disorders. The authors present the use of melatonin both in the context of causal and symptomatic treatment and discuss melatonin supplementation: Dosage patterns, effectiveness, and safety. Sleep disorders may have a different clinical picture, so the assessment of exogenous melatonin efficacy should also refer to a specific group of symptoms. The review draws attention to the wide range of doses of melatonin used in supplementation and the need to introduce unified standards especially in the group of pediatric patients.

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Gastrointestinal dysfunctions as a risk factor for sleep disorders in children with idiopathic autism spectrum disorder: A retrospective cohort study

Autism ◽

10.1177/1362361316667061 ◽

2017 ◽

Vol 21 (8) ◽

pp. 1010-1020 ◽

Cited By ~ 11

Author(s):

Lena M McCue ◽

Louise H Flick ◽

Kimberly A Twyman ◽

Hong Xian

Keyword(s):

Quality Of Life ◽

Autism Spectrum Disorder ◽

Confidence Interval ◽

Sleep Disorders ◽

Sleep Disorder ◽

Behavioral Problems ◽

Sleep Problems ◽

Autism Spectrum ◽

Spectrum Disorder

Sleep disorders often co-occur with autism spectrum disorder. They further exacerbate autism spectrum disorder symptoms and interfere with children’s and parental quality of life. This study examines whether gastrointestinal dysfunctions increase the odds of having sleep disorders in 610 children with idiopathic autism spectrum disorder, aged 2–18 years, from the Autism Genetic Resource Exchange research program. The adjusted odds ratio for sleep disorder among those with gastrointestinal dysfunctions compared to those without was 1.74 (95% confidence interval: 1.22–2.48). In addition, the odds of having multiple sleep disorder symptoms among children with gastrointestinal dysfunctions, adjusted for age, gender, behavioral problems, bed wetting, current and past supplements, and current and past medications for autism spectrum disorder symptoms were 1.75 (95% confidence interval: 1.10–2.79) compared to children without gastrointestinal dysfunctions. Early detection and treatment of gastrointestinal dysfunctions in autism spectrum disorder may be means to reduce prevalence and severity of sleep problems and improve quality of life and developmental outcomes in this population.

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Sleep Disorders in Children With Autism Spectrum Disorder: Insights From Animal Models, Especially Non-human Primate Model

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2021.673372 ◽

2021 ◽

Vol 15 ◽

Author(s):

Shufei Feng ◽

Haoyu Huang ◽

Na Wang ◽

Yuanyuan Wei ◽

Yun Liu ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Animal Models ◽

Sleep Disorders ◽

Sleep Problems ◽

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Spectrum Disorder ◽

Children With Asd ◽

Human Primate

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder with deficient social skills, communication deficits and repetitive behaviors. The prevalence of ASD has increased among children in recent years. Children with ASD experience more sleep problems, and sleep appears to be essential for the survival and integrity of most living organisms, especially for typical synaptic development and brain plasticity. Many methods have been used to assess sleep problems over past decades such as sleep diaries and parent-reported questionnaires, electroencephalography, actigraphy and videosomnography. A substantial number of rodent and non-human primate models of ASD have been generated. Many of these animal models exhibited sleep disorders at an early age. The aim of this review is to examine and discuss sleep disorders in children with ASD. Toward this aim, we evaluated the prevalence, clinical characteristics, phenotypic analyses, and pathophysiological brain mechanisms of ASD. We highlight the current state of animal models for ASD and explore their implications and prospects for investigating sleep disorders associated with ASD.

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Employment status is related to sleep problems in adults with autism spectrum disorder and no comorbid intellectual impairment

Autism ◽

10.1177/1362361317745857 ◽

2018 ◽

Vol 23 (2) ◽

pp. 531-536 ◽

Cited By ~ 5

Author(s):

Emma K Baker ◽

Amanda L Richdale ◽

Agnes Hazi

Keyword(s):

Autism Spectrum Disorder ◽

Sleep Disorders ◽

Sleep Disorder ◽

Sleep Problems ◽

Autism Spectrum ◽

International Classification ◽

Spectrum Disorder ◽

Adults With Autism ◽

Study Participants

Both sleep problems and unemployment are common in adults with autism spectrum disorder; however, little research has explored this relationship in this population. This study aimed to explore factors that may be associated with the presence of an International Classification of Sleep Disorders–Third Edition defined sleep disorder in adults with autism spectrum disorder (IQ > 80). A total of 36 adults with autism spectrum disorder and 36 controls were included in the study. Participants completed a 14-day actigraphy assessment and questionnaire battery. Overall, 20 adults with autism spectrum disorder met the International Classification of Sleep Disorders–Third Edition criteria for insomnia and/or a circadian rhythm sleep-wake disorder, while only 4 controls met criteria for these disorders. Adults with autism spectrum disorder and an International Classification of Sleep Disorders–Third Edition sleep disorder had higher scores on the Pittsburgh Sleep Quality Index and were more likely to be unemployed compared to adults with autism spectrum disorder and no sleep disorder. The findings demonstrate, for the first time, that sleep problems are associated with unemployment in adults with autism spectrum disorder. Further research exploring the direction of this effect is required; sleep problems that have developed during adolescence make attainment of employment for those with autism spectrum disorder difficult, or unemployment results in less restrictions required for optimal and appropriate sleep timing.

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Sleep Problems and Their Correlates in Children with Autism Spectrum Disorder: An Indian Study

Journal of Autism and Developmental Disorders ◽

10.1007/s10803-018-3820-6 ◽

2018 ◽

Vol 49 (3) ◽

pp. 1169-1181 ◽

Cited By ~ 6

Author(s):

Vernika Tyagi ◽

Monica Juneja ◽

Rahul Jain

Keyword(s):

Autism Spectrum Disorder ◽

Sleep Problems ◽

Children With Autism ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Indian Study

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Influence of sleep disorders on the behavior of individuals with autism spectrum disorder

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2015.00347 ◽

2015 ◽

Vol 9 ◽

Cited By ~ 22

Author(s):

Cintia C. Fadini ◽

DionÃsia A. LamÃ´nica ◽

Agnes C. Fett-Conte ◽

Elaine OsÃ³rio ◽

Gabriela M. Zuculo ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Sleep Disorders ◽

Autism Spectrum ◽

Spectrum Disorder

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Sleep Problems in 2- to 5-Year-Olds With Autism Spectrum Disorder and Other Developmental Delays

10.1542/9781610024716-part05-ch016 ◽

2020 ◽

pp. 204-212

Author(s):

Ann M. Reynolds ◽

Gnakub N. Soke ◽

Katherine R. Sabourin ◽

Susan Hepburn ◽

Terry Katz ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Developmental Delays ◽

Sleep Problems ◽

Autism Spectrum ◽

Spectrum Disorder

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Umbrella systematic review of systematic reviews and meta-analyses on comorbid physical conditions in people with autism spectrum disorder

The British Journal of Psychiatry ◽

10.1192/bjp.2020.167 ◽

2020 ◽

Vol 218 (1) ◽

pp. 10-19 ◽

Cited By ~ 1

Author(s):

Ewelina Rydzewska ◽

Kirsty Dunn ◽

Sally-Ann Cooper

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorder ◽

Systematic Reviews ◽

Sleep Problems ◽

Evidence Base ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Physical Conditions ◽

Sensory Impairments ◽

Meta Analyses

BackgroundComorbid physical conditions may be more common in people with autism spectrum disorder (ASD) than other people.AimsTo identify what is and what is not known about comorbid physical conditions in people with ASD.MethodWe undertook an umbrella systematic review of systematic reviews and meta-analyses on comorbid physical conditions in people with ASD. Five databases were searched. There were strict inclusion/exclusion criteria. We undertook double reviewing for eligibility, systematic data extraction and quality assessment. Prospective PROSPERO registration: CRD42015020896.ResultsIn total, 24 of 5552 retrieved articles were included, 15 on children, 1 on adults, and 8 both on children and adults. Although the quality of included reviews was good, most reported several limitations in the studies they included and considerable heterogeneity. Comorbid physical conditions are common, and some are more prevalent than in the general population: sleep problems, epilepsy, sensory impairments, atopy, autoimmune disorders and obesity. Asthma is not. However, there are substantial gaps in the evidence base. Fewer studies have been undertaken on other conditions and some findings are inconsistent.ConclusionsComorbid physical conditions occur more commonly in people with ASD, but the evidence base is slim and more research is needed. Some comorbidities compound care if clinicians are unaware, for example sensory impairments, given the communication needs of people with ASD. Others, such as obesity, can lead to an array of other conditions, disadvantages and early mortality. It is essential that potentially modifiable physical conditions are identified to ensure people with ASD achieve their best outcomes. Heightening clinicians’ awareness is important to aid in assessments and differential diagnoses, and to improve healthcare.

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