0
Original Investigation |

Maintenance Treatment With Varenicline for Smoking Cessation in Patients With Schizophrenia and Bipolar Disorder:  A Randomized Clinical Trial

A. Eden Evins, MD, MPH1; Corinne Cather, PhD1; Sarah A. Pratt, PhD2; Gladys N. Pachas, MD1; Susanne S. Hoeppner, PhD1; Donald C. Goff, MD3; Eric D. Achtyes, MD, MS4; David Ayer, PhD5; David A. Schoenfeld, PhD1
[+] Author Affiliations
1Massachusetts General Hospital and Harvard Medical School, Boston
2Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire
3New York University Langone Medical Center, New York
4Cherry Street Health Services and Michigan State University College of Human Medicine, Grand Rapids
5Centerstone Research Institute and Indiana University, Bloomington
JAMA. 2014;311(2):145-154. doi:10.1001/jama.2013.285113.
Text Size: A A A
Published online

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

Figures in this Article

Sign In to Access Full Content

Don't have Access?

Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more

Subscribe for full-text access to content from 1998 forward and a host of useful features

Activate your current subscription (AMA members and current subscribers)

Purchase Online Access to this article for 24 hours

Figures

Place holder to copy figure label and caption
Figure 1.
Study Flow Chart

The reasons patients withdrew include that they did not want to attend or take placebo, they moved, or no reason was provided. The reasons for administrative withdrawal include poor medication adherence, poor attendance, medical instability, or site closure. Four participants who were considered withdrawn for adverse-events during the open-phase segment gave more than 1 reason for withdrawing.aData from 7 participants, 1 of whom had relapsed and 6 of whom had been continuously abstinent, were included in the primary analysis measured by imputation as relapsed at the time they dropped out.bData from these 19 participants, 17 of whom had relapsed and 2 of whom had been continuously abstinent, were included in the primary analysis by imputation as relapsed at the time of dropout.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Point-Prevalence and Continuous Abstinence Rates During Study Treatment and Follow-up Phases

At week 16, cognitive behavioral therapy sessions were tapered to twice a month; at week 20, to once a month. P values are based on Fisher exact tests. Seven-day point-prevalence was higher for those assigned to varenicline at week 52 (P < .001) and at week 64 (P < .01). Continuous abstinence was higher for those assigned to the varenicline group from weeks 12 through 52 (P < .01), weeks 12 through 64 (P < .01), and weeks 12 through 76 (P < .05). There were 40 participants in the varenicline and 47 in the placebo group throughout the relapse-prevention and follow-up phases, and there were 203 participants in the open-label phase.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Clinical Outcomes During the Open-Label, Randomized, Follow-up Phases

At week 16, cognitive behavior therapy sessions were tapered to twice a month; at week 20, to once a month. Data presented are raw means. Error bars represent 95% confidence intervals. The 12-Item Short Form Health Survey is scored via a standard algorithm, with higher scores indicating better patient self perception of health, with a mean score of 50 and a standard deviation of 10 in a representative sample of the US population. See the legend in Table 1 for score definitions for Brief Psychiatric Rating Scale, and the Calgary Depression Scale for Schizophrenia.

Graphic Jump Location

Tables

References

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 1

Sign In to Access Full Content

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics
PubMed Articles
Jobs
brightcove.createExperiences();