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

Berk, Michael; Ng, Felicity; Wang, Wei V.; Tohen, Mauricio; Lubman, Dan I.; Vieta, Eduard; Dodd, Seetal

doi:10.1016/j.jad.2008.01.018

« Previous Next »Journal of Affective Disorders
Volume 110, Issue 1 , Pages 126-134, September 2008

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

Michael Berk
- University of Melbourne, Victoria, Australia
- Barwon Health and The Geelong Clinic, Australia
- ORYGEN Research Centre, Parkville, Australia
- Mental Health Research Institute, Parkville, Australia
Felicity Ng
- University of Melbourne, Victoria, Australia
- Barwon Health and The Geelong Clinic, Australia
- 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.
Wei V. Wang
- Lilly Research Laboratories Indianapolis IN, USA
Mauricio Tohen
- Lilly Research Laboratories Indianapolis IN, USA
- McLean Hospital, Harvard Medical School, Belmont MA, USA
Dan I. Lubman
- University of Melbourne, Victoria, Australia
- ORYGEN Research Centre, Parkville, Australia
Eduard Vieta
- University of Barcelona, Hospital Clinic, IDIBAPS, CIBER-SAM, Spain
Seetal Dodd
- University of Melbourne, Victoria, Australia
- Barwon Health and The Geelong Clinic, Australia

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.