Independent Effects of Tobacco Abstinence and Bupropion on Cognitive Function in Schizophrenia

A. Eden Evins, M.D., M.P.H.; Thilo Deckersbach, Ph.D.; Corinne Cather, Ph.D.; Oliver Freudenreich, M.D.; Melissa A. Culhane, M.P.H.; David C. Henderson, M.D.; Michael F. Green, Ph.D.; David A. Schoenfeld, Ph.D.; Nancy A. Rigotti, M.D.; and Donald C. Goff, M.D.

Objective: The objective of this study was to examine the effects of tobacco abstinence and bupropion treatment on cognitive functioning in adult smokers with schizophrenia in the setting of a randomized, double-blind, placebo-controlled clinical trial of bupropion for smoking cessation.

Method: Fifty-three adults with schizophrenia (DSM-IV) took part in a trial of bupropion for smoking cessation. Subjects were enrolled in the study from August 1999 to March 2003. Forty-five subjects remained in the trial at week 4; 41 subjects, 19 taking bupropion and 22 taking placebo, completed the baseline and week 4 cognitive assessments and were included in the analysis of adjusted effects of abstinence and bupropion treatment on cognitive function.

Results: Controlling for bupropion treatment and baseline performance, 7 days of tobacco abstinence was associated with slowed motor speed (finger tapping) but was not associated with worsening of performance on tests of attention (AX Continuous Performance Test [AX-CPT]), verbal learning and memory (California Verbal Learning Test [CVLT]), working memory (digit span), or executive function/inhibition (Stroop) and was not associated with worsening of any clinical measures. Controlling for abstinence status, bupropion was associated with reduction (improvement) in reaction time variability on the AX-CPT and with reduction in perseverative errors on the CVLT.

Conclusion: We conclude that 1 week of tobacco abstinence is associated with slowed motor speed but is not associated with detectable worsening in performance on a range of neuropsychological tests or clinical symptoms in the subset of patients who were able to quit smoking. We also conclude that bupropion treatment may be associated with improvement in variability of attention.

(J Clin Psychiatry 2005;66:1184-1190)

Received Aug. 10, 2004; accepted March 7, 2005. From the Schizophrenia Program (Drs. Evins, Deckersbach, Cather, Freudenreich, Henderson, and Goff and Ms. Culhane), the Addictions Research Program (Dr. Evins and Ms. Culhane), the Tobacco Treatment and Research Center (Drs. Evins and Rigotti), and the Biostatistics Center (Dr. Schoenfeld), Massachusetts General Hospital, Boston; Harvard Medical School, Boston, Mass. (Drs. Evins, Deckersbach, Cather, Freudenreich, Henderson, Schoenfeld, Rigotti, and Goff); and the Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles (Dr. Green).

This work was supported by a Young Investigator Award from the National Alliance for Research on Schizophrenia and Affective Disorders, Great Neck, N.Y., by Department of Health and Human Services Substance Abuse and Mental Health Services Administration grant 05B1MACMHS-04, and by National Institute on Drug Abuse grants RO3 DA12542 and K23 DA00510 (Dr. Evins); National Institute of Mental Health grant K24 MH02025 (Dr. Goff); and National Heart, Lung, and Blood Institute grant K24 HL04440 (Dr. Rigotti). GlaxoSmithKline (Research Triangle Park, N.C.) provided sustained-release bupropion and placebo tablets.

This work has been presented in part at the 9th annual meeting of the Society for Research on Nicotine and Tobacco, New Orleans, La., Feb. 19-22, 2003, and the 156th annual meeting of the American Psychiatric Association, San Francisco, Calif., May 17-22, 2003.

Financial disclosure appears at the end of this article.

The authors acknowledge Dr. Kenneth Duckworth, M.D., and Dr. Joan Kerzner, Ph.D., from the Massachusetts Department of Mental Health, Boston, for their support of the project.

Corresponding author and reprints: A. Eden Evins, M.D., MGH Schizophrenia Program, 25 Staniford Street, Boston, MA 02114 (e-mail: a_eden_evins@hms.harvard.edu).