Between 72% and 90% of schizophrenia patients smoke cigarettes, compared with 24% in the general population. Mortality from coronary disease, pulmonary disease and cancer is 2-6 times higher in schizophrenia patients than age matched controls. Although patients with schizophrenia can be both highly motivated and persistent in attempts to quit smoking, they have had relatively low smoking cessation rates of approximately 20% during treatment and high relapse rates of approximately 75% with standard treatments. We have found that a combined regimen of bupropion and dual nicotine replacement therapies (NRT) is well tolerated and associated with a 52% abstinence rate, a cessation rate comparable to that seen in the general population. While this cessation rate is excellent, 31% of those who were abstinent during treatment relapsed during NRT dose reduction and 77% relapsed by 12 months. Our hypothesis is that decreased nicotinic responsiveness underlies the high rates of relapse to smoking observed in schizophrenia. Because schizophrenia patients have reduced nicotinic responsiveness that is not expected to return to normal after smoking cessation, continuation of a nicotinic agonist may reduce rates of relapse to smoking. Standard treatment for smoking cessation in the general population involves 8-12 weeks of therapy. It is our hypothesis, based on the high rate of relapse to smoking during taper and immediately after discontinuation of pharmacotherapy, and on convincing evidence for a nicotinic receptor dysfunction in schizophrenia, that longer duration of pharmacotherapy is needed to prevent relapse to smoking in patients with schizophrenia. To assess this possibility, we propose to evaluate the safety and efficacy of 12 months of bupropion combined with dual NRT in schizophrenia patients who are able to quit smoking with open treatment. To do so, we will enroll 260 smokers with schizophrenia into an open, 8-week smoking cessation program that includes bupropion, NRT patch, prn NRT nasal spray and group cognitive behavioral therapy. Those who are abstinent at the end of the open intervention (n=91-104) will be randomized to a 44 week, double blind, placebo-controlled trial of bupropion, NRT patch and prn NRT nasal spray at the dose used to quit smoking. Participants will then discontinue study medications and enter a 3-month follow up. The primary outcome measure will be 7-day point prevalence abstinence rate at 12 months in the intervention vs. placebo groups.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA021245-04
Application #
7848973
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Walton, Kevin
Project Start
2007-09-01
Project End
2013-09-30
Budget Start
2010-06-01
Budget End
2013-09-30
Support Year
4
Fiscal Year
2010
Total Cost
$751,014
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Thorndike, Anne N; Achtyes, Eric D; Cather, Corinne et al. (2016) Weight gain and 10-year cardiovascular risk with sustained tobacco abstinence in smokers with serious mental illness: a subgroup analysis of a randomized trial. J Clin Psychiatry 77:e320-6
Volkow, Nora D; Swanson, James M; Evins, A Eden et al. (2016) Effects of Cannabis Use on Human Behavior, Including Cognition, Motivation, and Psychosis: A Review. JAMA Psychiatry 73:292-7
Evins, A Eden; Cather, Corinne; Laffer, Alexandra (2015) Treatment of tobacco use disorders in smokers with serious mental illness: toward clinical best practices. Harv Rev Psychiatry 23:90-8
Evins, A Eden; Hong, L Elliot; Kelly, Deanna L (2015) T. Kishi and N. Iwata: Varenicline for smoking cessation in people with schizophrenia: systematic review meta-analysis. Eur Arch Psychiatry Clin Neurosci 265:269-70
Evins, A Eden; Cather, Corinne; Pratt, Sarah A et al. (2014) Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial. JAMA 311:145-54
Pachas, Gladys N; Cather, Corinne; Pratt, Sarah A et al. (2012) Varenicline for Smoking Cessation in Schizophrenia: Safety and Effectiveness in a 12-Week, Open-Label Trial. J Dual Diagn 8:117-125
Dutra, Sunny J; Stoeckel, Luke E; Carlini, Sara V et al. (2012) Varenicline as a smoking cessation aid in schizophrenia: effects on smoking behavior and reward sensitivity. Psychopharmacology (Berl) 219:25-34