Benefits of Melatonin as a Sleep Aid for Children with Autism Spectrum Disorder

This paper examines the prevalence of poor sleep latency, duration, and fragmentation in children diagnosed with autism. It explains the possible causes of sleep disturbances, and its effects on the child and families’ wellbeing. It explores studies that support the use of melatonin, provides instructions for proper use, and explains the limitation of studies presented as well as provides ideas for further research.

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with deficits in social and communication skills, stereotypical behaviors and limited interests (American Psychiatric Association 2000). Children with autism are at a higher risk of sleep disorders. Studies report that about 40-80% of children with autism have sleep difficulties.(Giannotti, Cortesi, Cerquiglini, & Bernabei, 2006) The most frequently reported issues in children with autism are sleep latency, difficulty falling asleep, sleep duration, a short amount of sleep and fragmentation, difficulty staying asleep. However, bed time resistance, insomnia, parasomnia, sleep disordered breathing, morning rise problems, and day time sleepiness are all common challenges.

Sleep difficulties negatively affect both children diagnosed with autism and their families. Children with autism sleep and average of 17-43 minutes less than other children their age (Cavalieri, 2016). Lack of sleep is one of the major distresses for families and the most frequently reported challenge faced by parents. Parents of children with autism who have sleep disturbances report more elevated levels of stress than parents of children with ASD, but without sleep difficulties(Giannotti, Cortesi, Cerquiglini, & Bernabei, 2006).

There is a strong association between sleeping difficulties in children with autism and their ability to function during the day. Studies have shown that childhood sleep disturbance have a great bearing on a child’s overall welfare(Cavalieri, 2016). Sleep disturbance effects a child’s health, behavior, attention, cognition, and school performance. Children diagnosed with autism and characterized as having sleep complications were significantly more physical aggressive, irritable, inattentive and hyperactive when compared to children diagnosed with autism alone. Sleep disturbance may increase core and related symptoms of autism. Intervention that are aimed at reducing sleep issues not only improve the child’s health and family life but also may reduce symptoms related to autism(Mazurek & Sohl, 2016).

The etiology of sleep issues in children with ASD is not fully understood. Different theories are currently being studied by scientist. One hypothesis is that disturbance of the circadian rhythms, as observed in children with ASD, might be due to the anomalies in the creation of melatonin. Studies have revealed that children with autism have low levels of nocturnal melatonin which might be credited to the lack of the ASMT gene which creates the enzyme involved in melatonin synthesis(Mazurek & Sohl, 2016).

Another hypothesis suggested is that synaptic plasticity, neurons which support the attainment of complex skills, seems to be affected in autistic individuals. Although autistic children use specific signal processing and exhibit repetitive responses to stimuli they are familiar with, their capacity to learn new skills is impaired. This may be that due to the atypical physiology and sleep problems in autism. Specifically, sleep fragmentation may lead to less connectivity which could hinder neural substrate from creating a distinctive pathways to process information(Doyen, et al., 2011).

In 1994 Melatonin therapy for children with neuro developmental disorders and continuing sleep difficulties was first introduced in the USA. Melatonin is a an over the counter, nutritional supplement that has become popular by parents of children with autism. Melatonin is a neurohormone recognized for regulating circadian and seasonal rhythms. Most of body’s melatonin is generated and secreted by the pineal gland in the brain. The circadian rhythm for the release of melatonin is coordinated with typical sleeping hours. Melatonin induces sleep by inhibiting the wakefulness generating system. Melatonin secretion gradually increases during the night, and steadily decreases during the second half of the night. Melatonin regulation may be abnormal in children with ASD; daytime elevation, decreased amplitude and lack of nighttime elevation have been noted. Specifically, it has been suggested that a later peak in the night of melatonin secretion may be responsible for sleep onset problems, while reduced rhythm amplitude may be related to night awakenings and early morning awaking(Giannotti, Cortesi, Cerquiglini, & Bernabei, 2006).

Although melatonin is not FDA approved, many studies examining the safety and efficacy of melatonin for children with neurodevelopmental delays have exhibited promising results. A meta- analysis of nine- double blinded, randomized, placebo controlled trails, examining 183 patients with intellectual disabilities, all participants exhibited a reduction in sleep latency by an average of 34 min and an increase in sleep time by an average of 50 min(Braam, et al., 2008). Additionally, five randomized double blind placebo controlled studies showed that sleep duration was increased significantly and sleep latency was significantly decreased in children and adolescent with developmental disorders(Doyen, et al., 2011). Six studies examining children with developmental disabilities reported statistically significant decrease in sleep latency from 22 min to 1 hour and 30 min and improvement in daytime behaviors(Garstang & Wallis, 2006, Gringras, et al., 2012, Malow B. , et al., 2011, Wasdell, Bomben, Freeman, Tai, & Weiss, 2008, Wright, et al., 2011). Five of those studies found melatonin to increase total sleep time from 20min to 1hour and 20 minutes in children with neurodevelopment disorders. The more severe the sleep problems the more favorable treatment outcome(Gringras, et al., 2012). In fast release synthetic melatonin, a full dose is released into the blood stream at once, and is s more useful in improving sleep onset delay. While controlled release melatonin, which mimics the body’s natural release of melatonin throughout the night, is more effective for nocturnal awakenings. Current studies have exemplified the success of using both the fast release and the controlled release in promoting and maintaining sleep in children with autism(Giannotti, Cortesi, Cerquiglini, & Bernabei, 2006). Assessing the long term effectiveness of melatonin; when melatonin was discontinued for some children treatment benefits were maintained for 12 and 24 month afterwards. Whereas other children, returned to the pre-treatment baseline. However, when melatonin was reinstated, it was once again effective(Cavalieri, 2016).

An improvement in mood and day time behavior was reported by the parents of children taking melatonin. Using standardized checklist parents reported significant reduction in attention- deficit hyperactivity, stereotyped, and compulsive behaviors(Malow B. , et al., 2011). Children improved mood, calmer demeanor, decreased irritability was attributed to better sleeping patterns. Significant improvement in depression, anxiety and withdrawal symptoms was exhibited during melatonin treatment in children Asperger syndrome. However, no improvement in the scores of Children Autistic Rating Scale ( CARS) were noted(Giannotti, Cortesi, Cerquiglini, & Bernabei, 2006).

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Melatonin is effective at amounts as low as .5 to 1mg. The most common quantity used was 2.5- 5mg. All studies started with low doses and raised the dose steadily. Maximum safe and effective dose used in studies was 15mg. On average the medication was dispensed 30 min to 1 hour before bedtime. Although side effect were hardly reported they can consist of; headaches, tiredness, dizziness, confusion , nausea, and tachycardia. However, most studies that used high purity melatonin no side effects were evident. After 6 weeks, or once a sleep cycle is established it is best practice to discontinue using melatonin even though long term use seems safe and may be required. Children whose understanding of environment is so impaired periodic melatonin treatment might be necessary throughout their lives. (Malow B. , et al., 2011)

 Much of existing research that studied sleep intervention in children with ASD has limitations. A small number of studies inspected the effectiveness of melatonin using thorough methodologies such as randomized, placebo control and blinded participants and providers. Most studies enrolled a heterogeneous population in term of age, sleep issues and co- morbidities. Greater sample sizes that study a more homogenous groups of children with autism with extended follow up time after the intervention is needed(Doyen, et al., 2011). Examination of the long term effects of melatonin treatment is required. Future longitudinal research is required to thoroughly examine predictors, benefits, and consequences (Doyen, et al., 2011). The long term side effects of taking melatonin on a daily basis on the endocrine system is important. (Leu, Beyderman, Surdyaka, Wang, & Marlow, 2011).

Additional research understanding the sleep process and the causes of sleep disorders in children with autism is needed. A more definite explanation of sleep problems would help providers and parents have more clarity in identifying better treatment options and creating a better plan of care.(Cavalieri, 2016). Doyen, et al., 2011, in his study reports that the mean onset of sleep disturbance is 17 months and mean age of regression for children with autism is 22 months, suggesting that there is a higher vulnerability during this period of life. Further studies concerning the importance of sleep in babies and its effects on their development and behavior would be enlightening.

Melatonin is easily accessible, cheap and has not shown to have any significant side effects. The benefit of using Melatonin as a treatment to increase sleep latency, duration, as well as daytime behaviors in children with autism is clearly demonstrated. Additional research, with greater sample sizes, targeting children with autism, and looking at long term benefits and consequences is needed to further validate Melatonin’s benefits. However, to provide a more global perspective, a comprehensive understanding of the sleep process and its effects on children with autism is required.

References

• American Psychiatric Association. (2013). Diagnostic and Statistical manual of mental disorders (5th ed.). Washington, DC: American Psychiatric Association.
• Braam, W., Didden, R., Maas, A., Korzillus, H., Smits, M., & Curfts, L. (2008). Exogenous melatonin for sleep probloms in individuals with intellectual disability: a meta- analysis. Developmental Medical Child Neurology, 51, 340-349.
• Cavalieri, A. (2016). Sleep Issues in Children with Autism Spectrum Disoerder. Pediatric Nursing, 42, 169-188.
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