Improved Depressive Symptoms in Adults with Schizophrenia During a Smoking Cessation Attempt with Varenicline and Behavioral Therapy

ABSTRACT

Objective: Smoking prevalence rates are elevated in individuals with schizophrenia spectrum disorders (SSD) compared with the general population, with attendant disproportionate smoking-related morbidity and mortality. Pharmacotherapies that improve abstinence rates in this population are underutilized, partly due to concerns about neuropsychiatric safety, particularly for those with comorbid depression or prior suicide attempt. Prospective assessment of the psychiatric safety profile of varenicline in those with SSD is needed. Methods: Adult smokers with SSD entered a 12-week trial of varenicline and behavioral therapy for smoking cessation. Depressive symptoms were assessed with the Calgary Depression Scale for Schizophrenia (CDSS) at baseline and weekly thereafter. Participants with baseline and one or more postbaseline CDSS assessments, n = 179, were included in a secondary analysis of change in depressive symptoms with varenicline treatment, adjusting for abstinence status and baseline depressive symptoms. Results: Twenty-seven percent of participants had a CDSS score at baseline consistent with current major depressive disorder, and more than half had a prior suicide attempt. Forty-one percent (74/179) achieved two or more weeks of continuous abstinence at the end of treatment. CDSS scores declined 31% during the 12-week treatment period. Controlling for baseline CDSS scores, depressive symptoms declined over time in those who completed the trial, independent of abstinence status, and either declined or remained unchanged in those with major depressive disorder or prior suicide attempt or who were taking antidepressant medication. Those who did not complete the trial had no change in depressive symptoms. Discussion: Depressive symptoms declined in adults with schizophrenia during 12 weeks of varenicline treatment and cognitive behavioral therapy, independent of tobacco abstinence. Smokers with SSD who have significant depressive symptoms may be successful in smoking cessation attempts with pharmacotherapeutic aids such as varenicline while maintaining stable psychiatric symptoms. This is a secondary analysis of data collected as part of a clinical trial registered as NCT00621777, at www.clinicaltrials.gov.

KEYWORDS:

• Schizophrenia
• nicotine
• smoking cessation
• varenicline
• major depressive disorder
• depressive symptoms
• abstinence

Acknowledgments

We would like to acknowledge Ivan Montoya, MD, acting director of the National Institute on Drug Abuse Division of Therapeutics and Medical Consequences, for his unflagging support for this project.

Disclosures

Dr. Evins, within the past five years, has received research study support to her institution from Pfizer, Forum Pharmaceuticals, GlaxoSmithKline, National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA), and Patient-Centered Outcomes Research Institute (PCORI) and has provided consulting and/or advisory board services to Pfizer and Reckitt Benckiser. Dr. Achtyes has received research grant support from Assurex, Janssen, Michigan State University, Pine Rest Foundation, Priority Health, University of Chicago, American Recovery and Reinvestment Act, Avanir, Centers for Medicare & Medicaid Services, Dartmouth College, Janssen, National Institute on Alcohol Abuse and Alcoholism, NIDA, NIMH, North Shore Long Island Jewish Health System, Otsuka, Pfizer, Vanguard Research Group, and University of Texas Southwestern. He has served on advisory boards to Roche and Vanguard Research Group. No other authors have conflicts of interest to declare.

Funding

This work was funded by the National Institute of Health–R01 DA021245 (Evins) and K24 DA030443 (Evins).