Facilitation of benzodiazepine discontinuation by melatonin - A new clinical approach

Background: Benzodiazepines are the most frequently used drug for the treat ment of insomnia. Prolonged use of benzodiazepine therapy is not recommende d. However, many patients, particularly older patients, have difficulties d iscontinuing therapy. Melatonin, a hormone that is produced at night by the pineal gland, promotes normal sleep in humans and augments sleep induction by benzodiazepine therapy. Objective: To assess whether the administration of melatonin could facilita te the discontinuation of benzodiazepine therapy in patients with insomnia. Methods: Thirty-four subjects receiving benzodiazepine therapy were enrolle d in the 2-period study. In period 1, patients received (double-blinded) me latonin (2 mg in a controlled-release formulation) or a placebo nightly for 6 weeks. They were encouraged to reduce their benzodiazepine dosage 50% du ring week 2, 75% during weeks 3 and 4, and to discontinue benzodiazepine th erapy completely during weeks 5 and 6. In period 2, melatonin was administe red (single-blinded) for 6 weeks to all subjects and attempts to discontinu e benzodiazepine therapy were resumed. Benzodiazepine consumption and subje ctive sleep-quality scores were reported daily by all patients. All subject s were then allowed to continue melatonin therapy and follow-up reassessmen ts were performed 6 months later. Results: By the end of period 1, 14 of 18 subjects who had received melaton in therapy, but only 4 of 16 in the placebo group, discontinued benzodiazep ine therapy (P = .006). Sleep-quality scores were significantly higher in t he melatonin therapy group (P = .04). Six additional subjects in the placeb o group discontinued benzodiazepine therapy when given melatonin in period 2. The 6-month follow-up assessments revealed that of the 24 patients who d iscontinued benzodiazepine and received melatonin therapy, 19 maintained go od sleep quality. Conclusion: Controlled-release melatonin may effectively facilitate discont inuation of benzodiazepine therapy while maintaining good sleep quality.