title: Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia or bipolar disorder: A randomised, placebo-controlled, blinded trial.
abstract: OBJECTIVE
  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.affiliation: 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.
authors.forename: Lone
authors.initials: L
authors.lastname: Baandrup
authors.affiliation: b Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812 , Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark.
authors.forename: Jane
authors.initials: J
authors.lastname: Lindschou
authors.affiliation: b Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812 , Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Winkel
authors.affiliation: b Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812 , Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.affiliation: 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.
authors.forename: Birte Y
authors.initials: BY
authors.lastname: Glenthoj
mesh_terms: D000328:Adult; D000368:Aged; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D001714:Bipolar Disorder / Q000188:drug therapy*; D003718:Denmark; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008550:Melatonin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy*; D013375:Substance Withdrawal Syndrome / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D001569:Benzodiazepines; D008550:Melatonin
keywords: benzodiazepine; cessation; discontinuation; melatonin; schizophrenia