Sleep dysfunction in Rett syndrome: a trial of exogenous melatonin treatment

Abstract

Nine girls with Rett syndrome (mean age, 10.1 years) were monitored 24 hours a day over a period of 10 weeks using wrist actigraphy. Baseline sleepwake patterns were assessed for 1 week. Subsequently, patients underwent a 4-week melatonin treatment period in a double-blind, placebocontrolled, crdssover protocol that employed a 1-week washout between treatment trials. Melatonin doses ranged from 2.5 to 7.5 mg, based upon individual body weight.

Melatonin Versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies: A Randomised Controlled Crossover Trial

“…A possible explanation for this is that their study used a standard dose of 5 mg slow-release melatonin, whereas the final doses in our study ranged from 2 to 10 mg (M = 7 mg). This maximum is greater than that used in most other studies of children with neurodevelopmental disorders (range = 1-6 mg: Camfield et al 1996, Dodge andWilson 2001;Andersen et al 2008, 7.5 mg McArthur andBudden 1998). This suggests that some children may require larger doses than those being suggested in the literature, and that there may be considerable variability in dose needed.…”

“…All but two participants improved on sleep latency (time to onset of sleep), but there were no differences in the number of wakenings. In another double blind study, sleep latency also improved significantly in a group of nine children with Rett syndrome following 1 month of melatonin (McArthur and Budden 1998). The third trial, which did not report sleep improvements with melatonin, only included six participants (Camfield et al1996).…”

Clinical and biological progress over 50 years in Rett syndrome

“…166 In one small clinical trial (n=9) melatonin appeared to improve total sleep time and efficiency in those worse at baseline without any adverse side effects. 170 Given the frequency and impacts of sleep dysfunction on child and family, our evidence base for management remains remarkably sparse.…”

Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015

“…Other trials have tested the effects of melatonin for nocturnal sleep disturbance in children with a range of neurodevelopmental difficulties. [154][155][156] Many of the children included in these studies had at least one comorbid disability (e.g., epilepsy, blindness), and all had disturbed sleep-wake patterns. Although considerable inter-individual variability was observed in the response to melatonin, all of the studies showed significant improvements in at least one sleep measure.…”

“…Melatonin was recommended at the OPTION level in the previous Practice Parameters for children with various neurologic disorders, 1 based upon four studies, [153][154][155][156] none of which was eligible for the current review, due to an insufficient number of participants or grouping of participants with different CRSWDs. One new eligible study was identified, 157 and melatonin was shown to improve select predefined CRITICAL outcomes (TST, ISL), although the confidence interval associated with both values crossed the threshold of the predetermined clinically significant minimal change (see Table 2).…”