title: Going up in smoke: tobacco smoking is associated with worse treatment outcomes in mania.
abstract: BACKGROUND
  This study aimed to compare the treatment responses between smokers and non-smokers in bipolar mania clinical trials.
  
  
  METHODS
  Post-hoc analysis was conducted on data collected from three double-blind, randomised controlled trials in bipolar mania that had similar inclusion criteria. Patients were randomised to olanzapine (N=70) or placebo (N=69) for 3 weeks in Trial 1, olanzapine (N=234) or haloperidol (N=216) for 12 weeks in Trial 2, and olanzapine (N=125) or divalproex (N=126) for 47 weeks in Trial 3. This study analysed the Young Mania Rating Scale (YMRS) total scores and Clinical Global Impressions scale for bipolar disorder (CGI-BP) mania severity scores between smokers and non-smokers for each trial and for the pooled data from all three trials, using a mixed-effects model repeated measures approach.
  
  
  RESULTS
  For the pooled data, non-smokers showed superior treatment outcomes on both the YMRS (P=0.002) and CGI-BP (P<0.001), as well as longer time to discontinuation for any cause utilising Kaplan-Meier survival curves. For the individual trials, non-smokers showed greater improvement than smokers on both CGI-BP and YMRS in both treatment arms of Trial 2 (CGI-BP: haloperidol P=0.011, olanzapine P=0.042; YMRS: haloperidol P=0.010, olanzapine P=0.019), and in the olanzapine arm of Trial 3 (CGI-BP: P=0.002; YMRS: P=0.006). No significant difference in outcomes was found between smokers and non-smokers in Trial 1.
  
  
  CONCLUSIONS
  Post-hoc design, categorical definition of smoking status, unavailable antipsychotic drug levels, confounding effects of trial medications and substance abuse.
  
  
  CONCLUSIONS
  Smoking appears to be associated with worse treatment outcomes in mania.
authors.affiliation: University of Melbourne, Victoria, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.forename: Felicity
authors.initials: F
authors.lastname: Ng
authors.forename: Wei V
authors.initials: WV
authors.lastname: Wang
authors.forename: Mauricio
authors.initials: M
authors.lastname: Tohen
authors.forename: Dan I
authors.initials: DI
authors.lastname: Lubman
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.forename: Seetal
authors.initials: S
authors.lastname: Dodd
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D015897:Comorbidity; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D015201:Meta-Analysis as Topic; D000077152:Olanzapine; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D016019:Survival Analysis; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D010919:Placebos; D001569:Benzodiazepines; D014635:Valproic Acid; D006220:Haloperidol; D000077152:Olanzapine