Effects of Topiramate on Smoking in Patients with Schizoaffective Disorder, Bipolar Type: Response to Khazaal and Zullino.

Abstract

To the Editors: We recently published a secondary analysis of expired breath carbon monoxide (CO) levels (a measure of smoking exposure) in patients with schizoaffective disorder, bipolar subtype, participating in a clinical trial of topiramate for treating psychiatric symptoms (1). Our analysis found that CO levels remained generally unchanged for participants on topiramate and placebo during the course of the trial. In our discussion, we noted that one limitation of the study was the assessment of smoking by CO level only. Khazaal and Zullino (this issue) further discuss concerns about the suitability of CO as a measure of changes in smoking. Khazaal and Zullino suggest that CO may be a poor indicator of smoking reduction because decreases may be attenuated through increased intensity with which those cigarettes are smoked (i.e. compensation). Because it is highly dependent on the recency of smoking, we agree that CO is a more labile measure of smoking exposure than other biochemical measures (e.g., cotinine). However, a significant change in smoking consumption (cigarettes per day, CPD) should still result in a noticeable change in CO levels, even with some change in the intensity of smoking. Studies of the efficacy of transdermal nicotine patch (2) and bupropion (3) for smoking cessation in smokers with schizophrenia have shown parallel decreases in CO level consistent with decreases in CPD. It is possible that topiramate was associated with small changes in CPD that were masked through smoking compensation, our small sample size, or the infrequent CO assessments. However, small changes in smoking consumption that do not result in decreases in CO levels may not be clinically significant in terms of beneficial health outcomes for patients. In other words, it is overall smoke exposure, as indicated by CO, that is the more valid marker of health risk, rather than cigarettes per day, regardless of how they may be smoked. In order to clarify the usefulness of topiramate for smoking cessation with smokers with psychiatric disorders, further research is needed. Clinical trials comparing topiramate to placebo should be conducted in larger samples of smokers with psychiatric disorders using multiple assessments of smoking at frequent time points. Patient-reported changes in smoking consumption (CPD) should be confirmed using CO and cotinine levels. Questions about changes in smoking intensity with topiramate can be assessed through smoking topography techniques. One study (4) has examined changes in smoking topography for topiramate (75mg/day) compared to placebo in nonpsychiatric smokers. Topiramate resulted in decreased puff volume and enhanced reward from smoking, but also no differences in total puffs per cigarette and increased withdrawal during smoking abstinence. Topiramate-induced changes in smoking topography have not been examined for smokers with psychiatric disorders. Finally, the main purpose of the clinical trial was to examine the efficacy of topiramate for mood and psychotic symptoms in patients with schizoaffective disorder. Patients were not necessarily motivated to quit smoking and were not provided with smoking cessation counseling. Future studies should examine the efficacy of topiramate in conjunction to behavioral smoking cessation counseling in patients with current motivation to quit smoking. While our data does not suggest spontaneous decreases in smoking or CO levels for smokers with schizoaffective disorder, future studies that address the limitations of our analysis would provide a clearer picture of the clinical usefulness of topiramate for smoking cessation in this population.