Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety.
Study Goal
The researchers aimed to determine whether age or low melatonin levels better predict response to prolonged-release melatonin (PRM), assess its long-term efficacy, and evaluate its safety in treating primary insomnia.
Results Summary
PRM significantly reduced sleep latency in elderly patients regardless of melatonin levels, with effects maintained over 6 months without tolerance. Low melatonin production was not a useful predictor of response. Most adverse events were mild, with no significant safety differences between PRM and placebo.
Population
Adult outpatients (aged 18-80 years) with primary insomnia, including a focus on elderly patients (55+ years).
Effective Dosage
Not specified in the abstract.
Duration
3 weeks initial treatment, followed by 26 weeks for continued evaluation.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
Prolonged release melatonin (PRM) | no change | sleep latency | patients with low endogenous melatonin (6-sulphatoxymelatonin [6-SMT] ≤8 µg/night) regardless of age | - | did not differ from the placebo | #1 |
Prolonged release melatonin (PRM) | decrease | sleep latency | elderly patients regardless of melatonin levels | -19.1 versus -1.7 min | significantly reduced | #2 |
Prolonged release melatonin (PRM) | increase | sleep latency and additional sleep and daytime parameters | patients | over the 6-month period | were maintained or enhanced | #3 |
Prolonged release melatonin (PRM) | neutral | adverse events | patients | - | were mild in severity | #4 |
Prolonged release melatonin (PRM) | no change | any safety outcome | patients | - | no clinically relevant differences | #5 |
melatonin therapy | neutral | low melatonin production regardless of age | insomnia patients | - | is not useful in predicting responses | #6 |
BACKGROUND: Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also may have low melatonin levels. The study investigated whether older age or low melatonin excretion is a better predictor of response to PRM, whether the efficacy observed in short-term studies is sustained during continued treatment and the long term safety of such treatment. METHODS: Adult outpatients (791, aged 18-80 years) with primary insomnia, were treated with placebo (2 weeks) and then randomized, double-blind to 3 weeks with PRM or placebo nightly. PRM patients continued whereas placebo completers were re-randomized 1:1 to PRM or placebo for 26 weeks with 2 weeks of single-blind placebo run-out. Main outcome measures were sleep latency derived from a sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of Life (World Health Organzaton-5) Clinical Global Impression of Improvement (CGI-I) and adverse effects and vital signs recorded at each visit. RESULTS: On the primary efficacy variable, sleep latency, the effects of PRM (3 weeks) in patients with low endogenous melatonin (6-sulphatoxymelatonin [6-SMT] <or=8 microg/night) regardless of age did not differ from the placebo, whereas PRM significantly reduced sleep latency compared to the placebo in elderly patients regardless of melatonin levels (-19.1 versus -1.7 min; P = 0.002). The effects on sleep latency and additional sleep and daytime parameters that improved with PRM were maintained or enhanced over the 6-month period with no signs of tolerance. Most adverse events were mild in severity with no clinically relevant differences between PRM and placebo for any safety outcome. CONCLUSIONS: The results demonstrate short- and long-term efficacy and safety of PRM in elderly insomnia patients. Low melatonin production regardless of age is not useful in predicting responses to melatonin therapy in insomnia. The age cut-off for response warrants further investigation.