Varenicline Treatment for Smoking Cessation in Patients With Bipolar Disorder
Condition: Smoking Cessation; Bipolar Disorder
MeSH terms: Bipolar Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      The investigators' hypothesis is that add-on varenicline will be effective (versus placebo)
      in initiating abstinence from smoking in subjects with stable, euthymic bipolar disorder who
      are motivated to quit smoking within four weeks. This primary outcome will be assessed from
      randomization to 12 weeks or end of the treatment phase of the study. Secondarily, the
      investigators also hypothesize that varenicline will prevent relapse in the subsequent
      12-weeks follow-up non-treatment phase. Furthermore, the investigators plan to test the
      effectiveness of varenicline in reducing nicotine withdrawal symptoms or urges to smoke, as
      well as its safety for use in stable bipolar patients when used as an add-on treatment for
      smoking cessation.

      The investigators plan to test these hypotheses by conducting a randomized,
      placebo-controlled add-on treatment trial of Chantix with 60 recruited subjects diagnosed
      with DSM-IV bipolar disorder for a period of three months. The investigators will follow-up
      with them three months later to evaluate extended abstinence.
    

Detailed description: 
      OBJECTIVE:

      Our primary objective is to determine if adjunctive varenicline will be efficacious (vs.
      placebo) in initiating abstinence from smoking cigarettes in subjects with stable bipolar
      disorder who are motivated to quit smoking during a 12-week treatment phase. A secondary
      outcome is to determine whether those who initiated abstinence during the 12-week treatment
      phase will maintain abstinence in the subsequent three-month follow-up period off study
      medications.

      Additional outcomes: we plan to test the effectiveness of varenicline in reducing nicotine
      withdrawal symptoms or urges to smoke, as well as its safety for use in stable bipolar
      patients when used as an adjunctive treatment for smoking cessation.

      RESEARCH PLAN:

      We plan to test these hypotheses by conducting a randomized, placebo-controlled, treatment
      trial of Chantix. Measures of CO levels in expired air (10 ppm or lower), self-reported
      abstinence, and psychopathology ratings will be used to evaluate primary and secondary
      outcomes along with safety assessments. Smoking abstinence is defined as 7-day point
      prevalence of self-reported no smoking verified objectively by expired CO levels of 10 ppm or
      less, and will be assessed at 12-weeks (or end of treatment phase) as the primary outcome.
      The same criterion will be used to assess maintenance of abstinence in the non-treatment
      phase, i.e. at 24 weeks or end of study.

      METHODS:

      Seventy-six subjects with DSM-IV bipolar disorder will be recruited from Western Psychiatric
      Institute and Clinic and Dubois Regional Medical Center. Using a 1:1 Randomization, which
      also takes into account gender, subjects who sign an informed consent document will be
      randomized to receive Chantix or placebo.

      It is expected that 16 of the 76 may not meet inclusion/exclusion criteria, leaving 60
      consenting adults aged 18-65 years with DSM-IV bipolar disorder, which will be confirmed by
      the MINI (Sheehan et al.) Subjects must meet smoking inclusion criteria of smoking 10 or more
      cigarettes per day. Motivation to quit smoking (score of at least 7 on the Contemplation
      Ladder Scale) as well as stable mood status (Young Mania Rating Scale score of eight or less,
      Montgomery Asberg Depression Rating Scale Score of eight or less, with low scores on suicide
      aggression and psychotic items over a four-week period required. Subjects who have received
      pharmacological agents for smoking cessation such as bupropion, nicotine replacement
      treatment, or who have participated in behavioral treatment for smoking cessation more than
      three months before beginning the study will be permitted to enroll in the study. Anyone
      experiencing serious side-effects from varenicline in the past or who has already
      participated in a smoking cessation study with varenicline will be excluded.

      Chantix or placebo will be administered using random assignment at a dose of 0.5 mg by mouth
      for three days, followed by 0.5 mg twice per day for four days. After the first week, the
      dose will be increased to 1 mg twice daily for 11 weeks. Subjects must be able to tolerate a
      minimum of 1 mg per day to continue in the study.

      Subjects will pick a target date between visit 3 (to permit titration to the target dose of 2
      mg per day) and visit 4 to quit smoking. There needs to be at least 24 hours (preferably 48)
      between the time of the last cigarette usage and visit 4, where a CO measurement will be
      taken.

      Those who are unable to quit at this time will be given an opportunity to pick additional
      quit dates. All visits will be scheduled a week apart and subjects will continue to take
      their double-blind medication and receive counseling sessions for smoking cessation. Study
      medication will be stopped after 12 weeks, and there will be weekly visits to evaluate
      abstinence.

      Some standard psychopathology rating scales and smoking rating scales will be administered to
      evaluate secondary aims such as the degree of nicotine withdrawal symptoms and the impact of
      residual symptoms on bipolar disorder. Safety will be assessed through the administration of
      specific mania and depression rating scales including and the Columbia -Suicide Severity
      Rating Scale, as well as a comprehensive health assessment. This includes a medical history
      and evaluation of laboratory measures. Any adverse effects of medication will be assessed by
      asking questions at each visit and if necessary, contacting the subject by phone outside the
      scheduled visits.

      SIGNIFICANCE The rate of cigarette smoking among people with psychiatric disorders remains
      exceedingly high; nearly two to four times as high as those in the general population.
      Patients with bipolar disorder may have the highest rates of smoking as compared with people
      with other psychiatric diagnoses. To date, there have been no treatment trials of adequate
      size to measure smoking cessation rates in people with bipolar disorder. If varenicline
      proves to be an effective in helping people with bipolar disorder to stop smoking, or even to
      reduce their smoking rates, this could play an important role in improving their health.
    

Intervention name(s): Varenicline; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Patients will be randomly assigned to receive either varenicline or placebo for 12 weeks. Patients assigned to varenicline will receive 0.5mg by the oral route once a day for 3 days, followed by 0.5mg twice a day for 4 days. After the first week the dose will be increased to 1mg twice daily for the remainder of the active treatment period of the study, i.e. 11 weeks. Patients assigned to placebo will receive identical looking capsules in a dosage schedule similar to varenicline. Patients will be instructed to take study medication after meals with a glass of water.; Patients will be randomly assigned to receive either varenicline or placebo for 12 weeks. Patients assigned to varenicline will receive 0.5mg by the oral route once a day for 3 days, followed by 0.5mg twice a day for 4 days. After the first week the dose will be increased to 1mg twice daily for the remainder of the active treatment period of the study, i.e. 11 weeks. Patients assigned to placebo will receive identical looking capsules in a dosage schedule similar to varenicline. Patients will be instructed to take study medication after meals with a glass of water.
Other intervention name(s): Chantix; Comparator
Intervention MeSH terms: Varenicline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Varenicline; Chantix; Smoking; Bipolar Disorder