Abstracts

Rationale: Dravet syndrome is a severe developmental and epileptic encephalopathy, in which 75% of patients have sleep disturbance. Melatonin is often used for sleep problems in childhood; however, there is no quality evidence supporting its use in Dravet syndrome.  We hypothesized that melatonin would increase total sleep and quality of life for patients with Dravet syndrome. Methods: A double-blind crossover randomized placebo-controlled trial was conducted, comparing 6 mg regular-release melatonin to placebo for patients with Dravet syndrome and sleep disturbance.  The primary outcome measure was total sleep measured by actigraphy, with secondary outcomes including wakefulness after sleep onset (WASO), Sleep Disturbance Scale in Children and Quality of Life in Children with Epilepsy-55 questionnaires, subjective caregiver report of clinical change, seizure diary and serum anti-epileptic drug levels.  We also compared actigraphy data of Dravet patients to age-matched healthy controls. Results: 13 patients completed the study.  There was no difference in total sleep or WASO between melatonin and placebo.  However, of the 11 patients for whom caregivers reported a clear clinical difference between treatments (blinded), 8/11 reported improvement on melatonin (p < 0.05).  For patients with reported benefit, the clinical improvement was often dramatic, with parents reporting “lives changed.”  Interestingly, when compared to controls, patients with Dravet syndrome had significantly increased total sleep (p = 0.002). Conclusions: Melatonin did not increase total sleep; however, blinded caregiver subjective reports indicate treatment with melatonin provided considerable clinical benefit for some patients with Dravet syndrome and sleep disturbance. Funding: This study was primarily funded by philanthropic donations to Prof. Scheffer’s Dravet syndrome research program, but also supported by funding from the National Health and Medical Research Council (NHMRC) Program Grants (628952, 1091593); Dr. Myers received salary support during the study from a Taking Flight Award from Citizens United for Research in Epilepsy (CURE; grant number 439534) and Prof. Scheffer holds a NHMRC Practitioner Fellowship (1104831).