Going up in smoke: Tobacco smoking is associated with worse treatment outcomes in mania

BackgroundThis study aimed to compare the treatment responses between smokers and non-smokers in bipolar mania clinical trials.MethodsPost-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.ResultsFor 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.LimitationsPost-hoc design, categorical definition of smoking status, unavailable antipsychotic drug levels, confounding effects of trial medications and substance abuse.ConclusionsSmoking appears to be associated with worse treatment outcomes in mania.