Prolonged-release melatonin for insomnia - an open-label long-term study of efficacy, safety, and withdrawal.
Level 3 - non-randomized controlled study
Prospective uncontrolled open-label extension cohort study
PubMed 21845053 · doi:10.2147/TCRM.S23036
What was done
A prospective, open-label study evaluated the efficacy, safety, and withdrawal phenomena of nightly prolonged-release melatonin (PRM, 2 mg) for 6 to 12 months, followed by a 2-week withdrawal period. Participants were 244 community-dwelling adults (aged 20–80) with primary insomnia who previously participated in a double-blind trial. Outcome measures were patient-reported sleep diary quality ratings, adverse events, vital signs, laboratory tests, withdrawal symptoms (CHESS-84), and nocturnal urinary 6-sulfatoxymelatonin excretion to assess endogenous melatonin production after discontinuation.
What was found
Of 244 patients, 36 dropped out, 112 completed 6 months, and 96 completed 12 months of treatment. The abstract reports that the mean number of nights with sleep quality rated as "good" or "very good" was significantly higher during PRM than before treatment, but reports no exact numerical values, effect sizes, or p-values. Discontinuation was not associated with rebound insomnia, withdrawal symptoms, or suppression of endogenous melatonin excretion.
Why it matters
This study provides evidence that up to 12 months of nightly prolonged-release melatonin treatment does not lead to tolerance, physical dependence, rebound insomnia, or suppression of endogenous melatonin synthesis upon cessation.
Limits
The study lacked a concurrent control or placebo group and was entirely open-label, introducing substantial risk of expectation and reporting bias for subjective sleep quality. The abstract provides no exact quantitative metrics or confidence intervals, and 36 of 244 participants (14.8%) dropped out before completing 6 months.
Cited by
- supports Studies evaluating melatonin supplementation up to one year indicate that endogenous melatonin production resumes normally when supplementation stops.