Objectives: The authors recently reported on efficacy and safety of prolonged-release melatonin formulation (PRM; Circadin 2mg) in elderly insomnia patients. The age cut-off for response to PRM and the long-term maintenance of efficacy and safety were further evaluated by looking at the total cohort (age 1880 years) from that study and subsets of patients aged 1854 and 5580 years (for whom the drug is currently indicated). Design: Randomised, double-blind, placebo controlled trial. Setting: Multicentre, outpatients, primary care setting. Methods: A total of 930 males and females aged 1880 years with primary insomnia who reported mean nightly sleep latency (SL) >20min were enrolled and 791 entered the active phase of the study. The study comprised a 2-week, single-blind placebo run-in period followed by 3 week's double-blind treatment with PRM or placebo, one tablet per day at 2 hours before bedtime. PRM patients continued whereas placebo completers were re-randomised 1:1 to PRM or placebo for 26 weeks followed by 2-weeks run-out on placebo. Main outcome measures: SL and other sleep variables derived from sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of life (WHO-5), Clinical Global Impression of Improvement (CGI-I) and adverse effects, recorded each visit, withdrawal and rebound effects during run-out. Results: In all, 746 patients completed the 3-week and 555 (421 PRM, 134 placebo) completed the 6-month period. The principal reason for drop-out was patient decision. At 3 weeks, significant differences in SL (diary, primary variable) in favour of PRM vs. placebo treatment were found for the 5580-year group (-15.4 vs. -5.5min, p0.014) but not the 1880-year cut-off which included younger patients. Other variables (SL-PSQI, PSQI, WHO-5, CGI-I scores) improved significantly with PRM in the 1880-year population, more so than in the 5580-year age group. Improvements were maintained or enhanced over the 6month period with no signs of tolerance. No withdrawal symptoms or rebound insomnia were detected. Most adverse events were mild with no significant differences between PRM and placebo groups in any safety outcome. Conclusions: The results demonstrate short- and long-term efficacy of PRM in insomnia patients aged 1880 years, particularly those aged 55 and over. PRM was well-tolerated over the entire 6-month period with no rebound or withdrawal symptoms following discontinuation.
- Melatonin insomnia
- Sleep latency