Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients

Objective: To describe the treatment response with melatonin for rapid eye movement (REM) sleep behavior disorder (RBD) associated with other neurologic disorders.

Background: Clonazepam has been considered the treatment of choice for RBD. However, an alternative treatment is desirable for those with RBD refractory to clonazepam, for those who experience intolerable side-effects with clonazepam, and for those in whom clonazepam precipitates or aggravates obstructive sleep apnea (OSA). To date, there is minimal published data and limited follow-up regarding the use of melatonin for patients with RBD associated with other neurologic syndromes and disorders.

Design/methods: The response to melatonin treatment for RBD was reviewed on consecutive patients the investigators treated with this agent at Mayo Clinic Rochester from January 2000 to June 2001. The coexisting neurologic disorders, reasons for using melatonin, effective doses, side-effects, and duration of follow-up were also reviewed on all patients.

Results: Fourteen patients were commenced on melatonin over the specified time period (13 male, median RBD onset age 56 years, range 20–77 years). The coexisting neurologic findings/disorders were dementia with Lewy bodies (n = 7), mild cognitive impairment with mild parkinsonism (n = 2), multiple system atrophy (n = 2), narcolepsy (n = 2), and Parkinson’s disease (n = 1). The reasons for using melatonin in these cases were incomplete response of RBD to clonazepam in six patients, existing cognitive impairment in five, intolerable side-effects with clonazepam in two, and presence of severe obstructive sleep apnea and narcolepsy in one. With seven patients continuing to use clonazepam at 0.5–1.0 mg/night, RBD was controlled in six patients, significantly improved in four, and initially improved but subsequently returned in two; no improvement occurred in one patient and increased RBD frequency/severity occurred in one patient. The effective melatonin doses were 3 mg in two cases, 6 mg in seven cases, 9 mg in one case, and 12 mg in two cases. Five patients reported side effects, which included morning headaches (2), morning sleepiness (2), and delusions/hallucinations (1); these symptoms resolved with
decreased dosage. The mean duration of follow-up was 14 months (range 9–25 months), with eight patients experiencing continued benefit
with melatonin beyond 12 months of therapy.

Conclusions: In this series, persistent benefit with melatonin beyond 1 year of therapy occurred in most but not all patients. Melatonin can
be considered as a possible sole or add-on therapy in select patients with RBD. Prospective, long-term, controlled trials with melatonin are
warranted in a larger number of patients with RBD associated with a variety of neurologic symptoms and disorders.