title: Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00621777.
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: A Eden
authors.initials: AE
authors.lastname: Evins
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Corinne
authors.initials: C
authors.lastname: Cather
authors.affiliation: Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Pratt
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Gladys N
authors.initials: GN
authors.lastname: Pachas
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Susanne S
authors.initials: SS
authors.lastname: Hoeppner
authors.affiliation: New York University Langone Medical Center, New York.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Goff
authors.affiliation: Cherry Street Health Services and Michigan State University College of Human Medicine, Grand Rapids.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Achtyes
authors.affiliation: Centerstone Research Institute and Indiana University, Bloomington.
authors.forename: David
authors.initials: D
authors.lastname: Ayer
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: David A
authors.initials: DA
authors.lastname: Schoenfeld
mesh_terms: D000328:Adult; D000368:Aged; D001552:Benzazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000150:complications*; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000627:therapeutic use; D011810:Quinoxalines / Q000627:therapeutic use; D012559:Schizophrenia / Q000150:complications*; D016540:Smoking Cessation / Q000379:methods*; D014029:Tobacco Use Disorder / Q000150:complications / Q000188:drug therapy* / Q000523:psychology*; D016896:Treatment Outcome; D000068580:Varenicline; D055815:Young Adult
chemical_list: D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D000068580:Varenicline