The profound effect of circadian timing and sleep on physical and mental health is well-known, including adverse metabolic and cardiovascular effects, depression, and learning impairment.1-3 Circadian rhythm sleep-wake disorders may develop when wakefulness and sleep patterns conflict with the timing of one’s biological clock.
Melatonin and other melatonin receptor agonists have demonstrated efficacy in the treatment of these disorders in both pediatric and adult populations.4 In a review published in July 2020 in Sleep Medicine Clinics, the authors discussed the use of these agents in patients with intrinsic circadian rhythm sleep-wake disorders.4
While other drugs such as hypnotics and alerting medications may also be used as “chronobiotics” (ie, agents that can shift central circadian timing and improve sleep), they are not discussed in the current review because of the lack of clinical trials investigating their use for these indications.
Based on available evidence, the American Academy of Sleep Medicine (AASM) clinical guidelines recommend strategically timed melatonin or other melatonin receptor agonists for delayed sleep-wake phase disorder (DSWPD) in children and adults, irregular sleep-wake rhythm disorder (ISWRD) in children and adolescents with neurologic disorders, and non-24 sleep-wake disorder in blind adults.5
For adults with DSWPD, the recommendation is based on 3 studies that used 1 of 2 fast release methods. One was a 0.3mg or 3mg fast release taken 1.5 to 6.5 hours before baseline dim light melatonin onset [DLMO] for the first 2 weeks and then advanced 1 hour earlier in the following. The second was a 5mg fast release taken between 7 pm and 9 pm, advanced by ~1 hour following the first week.6-8
For children and adolescents with DSWPD, the recommendation is based on 3 pediatric studies that used a 0.15mg/kg fast release taken 1.5 to 2.0 hours before habitual bedtime in children aged 6 to 12 years with no comorbidities, or a 3mg or 5mg fast release taken at 6 pm or 7 pm for those with psychiatric comorbidities.9-11
In pediatric patients with ISWRD with neurologic disorders, the recommendation is based on 1 study involving a 2 to 10mg fast release taken ~30 minutes before the patient’s planned bedtime.12
Lastly, regarding adults with non-24 sleep-wake disorder, the recommendation is based on 3 studies used either 10mg taken 1 hour before the patient’s preferred bedtime, or 0.5mg or 5mg taken at 9 pm.13-15
“Given that accurate objective measures of sleep and circadian timing are not currently easily accessible, treatment success is best judged by symptom improvement,” according to review coauthor Helen J. Burgess, PhD. Dr Burgess is now a professor in the Department of Psychiatry and codirector of the Sleep and Circadian Rhythms Research Laboratory at the University of Michigan in Ann Arbor (she was employed by Rush University Medical Center in Chicago, Illinois, at the time of publication).
This article originally appeared on Neurology Advisor