Study of Varenicline (Champix) for Smoking Cessation/Reduction in Patients With Bipolar Disorder
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder; Bipolar Disorder
Study type: Interventional

Summary: 
      Bipolar Disorder is a chronic relapsing mental disorder characterized by periods of elevated,
      expansive and irritable mood, often alternating with periods of significant clinical
      depression. People with Bipolar Disorder are typically heavy smokers who have difficulty
      quitting, and this is associated with significant tobacco-related medical illness and death.

      The proposed study will be a double-blind, placebo-controlled 10-week clinical trial of the
      safety and efficacy of varenicline (Champix™) in thirty subjects with Bipolar I Disorder.
      This medication is the latest first-line pharmacotherapy for smoking cessation and has been
      shown to be efficacious for smoking cessation, but has not yet been systematically studied in
      persons with Bipolar Disorder.
    

Detailed description: 
      Varenicline (VAR) is a α4β2 central nicotinic acetylcholine receptor (nAChR) partial agonist.
      It is believed to mimic the effect of nicotine by stimulating nAChRs and releasing sufficient
      dopamine in order to reduce craving and withdrawal effects. In the past two years since the
      approval of VAR there have been some increasing concerns about this medication, particularly
      in psychiatric smokers. Besides the typical side effects of nausea and insomnia, it has been
      associated with treatment-emergent suicidality, aggression, psychosis, and induction of
      hypomania or mania.

      Study Design:

      Thirty nicotine-dependent cigarette smokers with Bipolar I Disorder will be enrolled (N=30).
      All subjects will be symptomatically stable prior to enrollment, and compliant with their
      mood-stabilizer medication treatment to minimize the chances of adverse outcomes. The
      treatment group would receive flexible doses of varenicline (VAR) ranging from one to four
      capsules (0.5-2.0 mg) orally per day. The control group would receive one to four capsules of
      placebo VAR (0 mg) orally per day. All subjects would receive weekly Cognitive Behavioral
      Therapy (CBT) offered in group format to help them deal with tobacco cravings and mood
      management. The target quit date would be set during Week 3 of the trial. Comprehensive
      neuropsychological assessment and laboratory testing will be given at baseline and ten weeks;

      Hypotheses:

        1. Varenicline will be superior to placebo for smoking cessation outcomes.

        2. Varenicline will be well-tolerated and safe for use in Bipolar I smokers in comparison
           to placebo.

        3. Varenicline will reduce smoking indices (Carbon monoxide, cotinine) and have minimal
           effects on psychiatric symptomatology in mood-stabilizer treated Bipolar I smoking
           patients.

        4. The presence of prefrontal cortical, impulsivity and attentional deficits on the
           baseline neuropsychological battery will predict smoking cessation treatment failure in
           Bipolar I smokers.

      Significance:

        -  This would be the first placebo-controlled clinical trial using varenicline for the
           treatment of tobacco dependence in people with Bipolar Disorder.

        -  There is an immense need for a safe and effective smoking cessation therapy for smokers
           with bipolar illness. The co-morbidity between the major psychiatric disorders and
           nicotine dependence has been well established. The prevalence of cigarette smoking in
           patients with bipolar disorder is approximately 50-70% as compared to ~19% in the
           Canadian population. Moreover, smokers with Bipolar Disorder suffer to a higher extent
           from smoking-related illnesses than non-psychiatric smokers.
    

Intervention name(s): varenicline
Intervention type(s): Drug
Intervention description(s): One to four 0.5 mg capsules (0.5-2.0 mg) orally per day for ten weeks.
Other intervention name(s): Champix; Chantix
Intervention MeSH terms: Varenicline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Bipolar disorder; Bipolar-I; Varenicline; Champix; Chantix; Nicotine; Nicotinic receptor; Nicotinic receptor dysregulation; Dopamine; Acetylcholine; Cigarette; Smoking; Tobacco; Dependence; Neuropsychological function