Resumen de Maintenance Treatment With Varenicline for Smoking Cessation in Patients With Schizophrenia and Bipolar Disorder A Randomized Clinical Trial
Eden A. Evins, Corinne Cather, Sarah A. Pratt, Gladys N. Pachas, Susanne S. Hoeppner
Importance It is estimated that more than half of those with serious mental illness smoke tobacco regularly. Standard courses of pharmacotherapeutic cessation aids improve short-term abstinence, but most who attain abstinence relapse rapidly after discontinuation of pharmacotherapy.
Objective To determine whether smokers diagnosed with schizophrenia and bipolar disease have higher rates of prolonged tobacco abstinence with maintenance pharmacotherapy than with standard treatment.
Design, Setting, and Participants Randomized, double-blind, placebo-controlled, parallel-group, relapse-prevention clinical trial conducted in 10 community mental-health centers. Of 247 smokers with schizophrenia or bipolar disease recruited from March 2008-April 2012, 203 received 12-weeks’ open-label varenicline and cognitive behavioral therapy and 87 met abstinence criteria to enter the relapse prevention intervention.
Interventions Participants who had 2 weeks or more of continuous abstinence at week 12 of open treatment were randomly assigned to receive cognitive behavioral therapy and double-blind varenicline (1 mg, 2 per day) or placebo from weeks 12 to 52. Participants then discontinued study treatment and were followed up to week 76.
Main Outcomes and Measures Seven-day rate of continuous abstinence at study week 52, the end of the relapse-prevention phase, confirmed by exhaled carbon monoxide. Secondary outcomes were continuous abstinence rates for weeks 12 through 64 based on biochemically verified abstinence and weeks 12 through 76, based on self-reported smoking behavior.
Results Sixty-one participants completed the relapse-prevention phase; 26 discontinued participation (7 varenicline, 19 placebo) and were considered to have relapsed for the analyses; 18 of these had relapsed prior to dropout. At week 52, point-prevalence abstinence rates were 60% in the varenicline group (24 of 40) vs 19% (9 of 47) in the placebo group (odds ratio [OR], 6.2; 95% CI, 2.2-19.2; P < .001). From weeks 12 through 64, 45% (18 of 40) among those in the varenicline group vs 15% (7 of 47) in the placebo group were continuously abstinent (OR, 4.6; 95% CI, 1.5-15.7; P = .004), and from weeks 12 through 76, 30% (12 of 40) in the varenicline group vs 11% (5 of 47) in the placebo group were continuously abstinent (OR, 3.4; 95% CI, 1.02-13.6; P = .03). There were no significant treatment effects on psychiatric symptom ratings or psychiatric adverse events.
Conclusions and Relevance Among smokers with serious mental illness who attained initial abstinence with standard treatment, maintenance pharmacotherapy with varenicline and cognitive behavioral therapy improved prolonged tobacco abstinence rates compared with cognitive behavioral therapy alone after 1 year of treatment and at 6 months after treatment discontinuation.
Trial Registration clinicaltrials.gov Identifier: NCT00621777 Although tobacco smoking among adults has declined by 55% in the United States since 1965,1 smoking prevalence among adults with serious mental illness remains higher now than it was in the general population in 1965.2 Six million of the 11.4 million adults (53%) with serious mental illness smoke tobacco.3 Relatively small trials have reported pharmacologic cessation aids—including bupropion alone or combined with nicotine replacement therapy and varenicline—increase initial abstinence rates over behavioral treatment alone for smokers with schizophrenia and schizoaffective disorder, with mean abstinence rates of 24% at the end of 8 to 12 weeks of treatment vs 5% with placebo plus behavioral therapy, suggesting behavioral treatment alone is ineffective for smoking cessation in this population.4- 11 Abstinence rates in pharmacotherapy treatment groups declined from 24% to 12% 3 months after discontinuing pharmacotherapy,12 with some trials reporting the majority of relapses occurring within 2 weeks of stopping the medication,8 suggesting a possible need for longer-term pharmacotherapy for prolonged tobacco abstinence in this population.
In a recent trial, 12 weeks of maintenance treatment with varenicline improved abstinence rates at 1 year in smokers without psychiatric illness who attained initial abstinence with varenicline.13 An open-label trial involving recently abstinent smokers with serious mental illness found that maintenance therapy with bupropion, dual nicotine replacement therapy, and cognitive behavioral therapy (CBT) for 1 year resulted in a relapse rate of 35%,14 less than half the 77% relapse rate reported 12 months after discontinuation of a similar 12-week intervention,8 suggesting this approach may be feasible and effective in smokers with serious mental illness. The purpose of this study was to evaluate the efficacy of 40 weeks of maintenance varenicline and CBT in smokers with serious mental illness who achieved abstinence with 12 weeks of open-label varenicline and CBT.
