Varenicline as a smoking cessation aid in schizophrenia: effects on smoking behavior and reward sensitivity
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Smoking rates are up to five times higher in people with schizophrenia than in the general population, placing these individuals at high risk for smoking-related health problems. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, is a promising aid for smoking cessation in this population. To maximize treatment efficacy while minimizing risks, it is critical to identify reliable predictors of positive response to varenicline in smokers with schizophrenia.
Negative symptoms of schizophrenia are related to dysfunctions in the brain reward system, are associated with nicotine dependence, and may be improved by nicotine or nicotinic receptor agonists, suggesting that smoking cessation may be especially difficult for patients with substantial negative symptoms. The purpose of the study was to evaluate negative symptoms as predictors of response to varenicline.
Patients with schizophrenia (N = 53) completed a 12-week smoking cessation trial combining varenicline with cognitive behavioral therapy. Negative symptoms were assessed via the Scale for the Assessment of Negative Symptoms (Andreasen 1983). Outcomes included smoking abstinence as assessed by self-report and expired carbon monoxide. Change in performance on a probabilistic reward task was used as an index of change in reward sensitivity during treatment.
At week 12, 32 participants met criteria for 14-day point-prevalence abstinence. Patients with lower baseline symptoms of affective flattening (more typical affect) were more likely to achieve smoking abstinence and demonstrated larger increases in reward sensitivity during treatment.
These data suggest that affective flattening symptoms in smokers with schizophrenia may predict response to varenicline.
KeywordsNicotine Schizophrenia Varenicline Reward Anhedonia Affective flattening Smoking cessation
The study was funded by NIDA R01 DA021245 (Evins). This grant supported Dr. Evins’ effort on the project. During the study, Dr. Stoeckel was partially supported by the Harvard Medical School Zinberg Fellowship in Clinical Addiction Research and a NIDA Loan Repayment Program Grant, and Dr. Pizzagalli was partially supported by NIMH grants R01MH68376 and R21MH078979.
Disclosures/conflicts of interest
The authors declare no competing financial interests. Dr. Evins has received research support from GSK, Janssen and Pfizer, and honoraria or consulting fees from Boehringer-Ingelheim and Pfizer. Dr. Pizzagalli has received research support and consulting fees from ANT Inc. and honoraria and consulting fee from AstraZeneca.
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