Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia or bipolar disorder: A randomised, placebo-controlled, blinded trial

Abstract

Objectives. We assessed if prolonged-release melatonin can facilitate withdrawal of long-term benzodiazepine usage in patients with schizophrenia or bipolar disorder. Methods. Randomised, placebo-controlled, blinded, parallel superiority trial of 24 weeks duration. Participants were randomised to prolonged-release melatonin 2 mg daily versus matching placebo and were continuously guided to gradually reduce their usual benzodiazepine dosage. The primary outcome was mean benzodiazepine daily dosage at 24 weeks. Secondary outcomes included pattern of benzodiazepine dosage over time, benzodiazepine cessation proportion, and benzodiazepine withdrawal symptoms. Results. In total, 86 patients (21–74 years) were enrolled: 42 were randomised to melatonin versus 44 to placebo. We found no significant effect of melatonin on mean benzodiazepine dosage at 24 weeks (melatonin group 8.01 mg versus placebo group 5.72 mg diazepam equivalents; difference between means –2.29; 95% CI –5.78 to 1.21; P = 0.20). Benzodiazepine cessation proportion was 38.1% (16/42) in the melatonin group versus 47.7% (21/44) in the placebo group (OR 0.64; 95% CI 0.26 to 1.56; P = 0.32). Prolonged-release melatonin had no effect on benzodiazepine withdrawal symptoms. Conclusions. Benzodiazepine dosage was comparably low between the groups after 24 weeks of guided gradual dose reduction. In this context, prolonged-release melatonin did not seem to further facilitate benzodiazepine discontinuation.

Key words::

• benzodiazepine
• discontinuation
• cessation
• melatonin
• schizophrenia

Acknowledgements

None.

Statement of Interest

All authors have no relationships with companies that might have interest in the submitted work; all authors have no non-financial interests that may be relevant to the submitted work. The Research Fund of the Mental Health Services of the Capital Region in Denmark financed the trial with a postdoc grant and a grant for external randomisation and database management. Further funding was obtained with a grant from Axel Thomsen and Martha Thomsen's Foundation. The Lundbeck Foundation Centre of Clinical Intervention and Neuropsychiatric Schizophrenia Research covered residual expenses. The funding bodies had no role in trial design or in the collection, analysis and interpretation of data.