A Study of Varenicline for Prevention of Relapse to Smoking in Patients With Schizophrenia or Bipolar Disorder
Condition: Schizophrenia; Schizoaffective Disorder; Bipolar Disorder; Smoking
MeSH terms: Recurrence; Schizophrenia; Bipolar Disorder; Psychotic Disorders
Intervention: Varenicline; Placebo
Intervention description: At each weekly study visit from the baseline visit to study week 11, ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks.
In addition, participants who enter the relapse prevention phase and are randomized to the varenicline condition will receive varenicline at the dose used to attain initial abstinence for 40 weeks.; At each weekly study visit from the baseline visit to study week 11,ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks.
In addition, participants who enter the relapse prevention phase and are randomized to the placebo condition will receive placebo pills for 40 weeks.
Intervention MeSH terms: Varenicline
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 247.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: schizophrenia; bipolar disorder; varenicline; smoking cessation; relapse prevention; cognitive behavioral therapy

Summary:

      Varenicline (Chantix) is a smoking cessation treatment that was approved in 2006 by the FDA
      for treatment of nicotine dependence and may be particularly beneficial in smokers with
      schizophrenia or bipolar disorder. Early experience with varenicline indicates that it will
      be effective for smoking cessation in schizophrenia and in addition, has the potential to be
      therapeutic for cognitive dysfunction in this population. In addition, more data is needed to
      evaluate the safety, tolerability and effectiveness of Varenicline in people with bipolar
      disorder.

      To assess this possibility, we will evaluate the safety and efficacy of 12 months of
      varenicline in schizophrenia or bipolar disorder patients who are able to quit smoking in the
      short term with this treatment. To do so, we will enroll 324 smokers with schizophrenia or
      bipolar disorder from 6 mental health clinics in Massachusetts, New Hampshire, Michigan and
      Minnesota into an open, 12-week smoking cessation program that includes varenicline added to
      weekly group cognitive behavioral therapy (CBT). Those who achieve at least 2 weeks of
      continuous abstinence during the last 2 weeks of the open intervention will be randomized to
      the relapse prevention phase: a 40-week, double blind, placebo-controlled trial of
      varenicline at the dose used to quit smoking added to a tapering CBT schedule. Participants
      will then discontinue study medications and behavioral treatment and enter a 3-month follow
      up phase.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Women and men aged 18-70

          -  DSM-IV diagnosis of schizophrenia, schizoaffective disorder or bipolar disorder by
             diagnostic interview and chart review

          -  Smoke at least 10 cigarettes per day

          -  Clinically stable, on a stable dose of antipsychotic (schizophrenia) or mood
             stabilizer (bipolar) medication for at least 1 month

          -  No current active suicidal ideation

          -  Expired air carbon monoxide (CO) concentration >9 ppm

          -  Willing to take study medications and set a quit date within 2-3 weeks of beginning
             treatment and be willing to participate in the relapse prevention and follow-up
             portions of the study

          -  Women of childbearing potential must have a negative urine pregnancy test at baseline
             and agree to use an approved form of contraception during the study.

        Exclusion Criteria:

          -  DSM-IV diagnosis of dementia, neurodegenerative disease, or other organic mental
             disorder

          -  Substance use disorder other than nicotine or caffeine in the last 6 months

          -  Major depressive disorder within the last 6 months

          -  Serious unstable medical illness including, cardiovascular, hepatic, renal,
             respiratory, endocrine, neurological, or hematological disease such that
             hospitalization for treatment of that illness is likely within the next 2 months

          -  Life-threatening arrhythmia or cerebro-vascular event within 6 months, cardiovascular
             event within 2 months or uncontrolled hypertension

          -  History of multiple head injuries with neurological sequelae, a single severe head
             injury with lasting neurological sequelae, or current CNS tumor

          -  Liver function tests elevated over twice normal

          -  Renal insufficiency with estimated creatinine clearance <40 ml/min

          -  Plan to continue use of tobacco products othe than cigarettes (e.g., cigar, pipe)

          -  Use of an investigational medication or device in the past 30 days

          -  Current suicidal or homicidal ideation