Lone Baandrup1, Jane Lindschou2, Per Winkel2, Christian Gluud2, Birte Y Glenthoj1. 1. a Centre for Neuropsychiatric Schizophrenia Research (CNSR) & Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), University of Copenhagen, Mental Health Centre Glostrup, Mental Health Services - Capital Region of Denmark , Glostrup , Denmark. 2. b Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812 , Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark.
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.
RCT Entities:
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.
Authors: Alexandre González-Rodríguez; José Haba-Rubio; Judith Usall; Mentxu Natividad; Virginia Soria; Javier Labad; José A Monreal Journal: Clocks Sleep Date: 2022-02-15
Authors: Laura Palagini; Raffaele Manni; Eugenio Aguglia; Mario Amore; Roberto Brugnoli; Stéphanie Bioulac; Patrice Bourgin; Jean-Arthur Micoulaud Franchi; Paolo Girardi; Luigi Grassi; Régis Lopez; Claudio Mencacci; Giuseppe Plazzi; Julia Maruani; Antonino Minervino; Pierre Philip; Sylvie Royant Parola; Isabelle Poirot; Lino Nobili; Giovanni Biggio; Carmen M Schroder; Pierre A Geoffroy Journal: Front Psychiatry Date: 2021-06-10 Impact factor: 4.157