The Effect of Melatonin on Benzodiazepine Discontinuation and Sleep Quality in Adults Attempting to Discontinue Benzodiazepines: A Systematic Review and Meta-Analysis

Abstract

Background Abrupt discontinuation of benzodiazepines often results in side effects including anxiety and insomnia, which can be barriers to discontinuation among long-term users. Melatonin improves the onset, duration, and quality of sleep. By preventing insomnia in those attempting to discontinue benzodiazepines, melatonin may facilitate benzodiazepine discontinuation.Objectives The primary objective was to determine the effect of melatonin compared with placebo on benzodiazepine discontinuation in adults attempting to discontinue benzodiazepines. The secondary objective was to determine the effect of melatonin on sleep quality in this population.Methods We searched PubMed, MEDLINE, EMBASE, PsychINFO, and ClinicalTrials.gov from inception to November 2014. We included randomized controlled trials published in English comparing melatonin with placebo that reported benzodiazepine discontinuation or sleep quality. Two reviewers independently screened trials, extracted data, and assessed the risk of bias.Results We included six trials randomizing 322 participants. The mean age of participants was approximately 64 years. The trials used varied tapering strategies to discontinue benzodiazepines over 4-10 weeks while using melatonin. Melatonin had no effect on the odds of successfully discontinuing benzodiazepines (odds ratio 0.72, 95% confidence interval 0.21-2.41, p = 0.59). There was important heterogeneity among the trials (I (2) = 76%). The effect of melatonin on sleep quality was inconsistent.Conclusions Melatonin had no effect on benzodiazepine discontinuation while the effect of melatonin on sleep quality was inconsistent. We cannot rule out a role of melatonin in improving benzodiazepine discontinuation or sleep quality owing to imprecise effect estimates. Larger, well-designed, and reported randomized controlled trials may provide more valid and precise estimates of the effect of melatonin on these outcomes.