Going up in smoke: Tobacco smoking is associated with worse treatment outcomes in mania
Received 6 December 2007; received in revised form 16 January 2008; accepted 16 January 2008.
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.
Limitations
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.
fMcLean Hospital, Harvard Medical School, Belmont MA, USA
gUniversity of Barcelona, Hospital Clinic, IDIBAPS, CIBER-SAM, Spain
Corresponding author. Department of Clinical and Biomedical Sciences: Barwon Health, University of Melbourne, Swanston Centre, PO Box 281, Geelong, Victoria 3220, Australia. Tel.: +61 3 5260 3143; fax: +61 3 5246 5165.
ABSTRACT