Study of Varenicline (Champix) for Smoking Cessation/Reduction in Patients With Bipolar Disorder
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A 10-Week Pilot Study of Varenicline (Champix) Versus Placebo for Smoking Cessation/Reduction in Patients With Bipolar Disorder|
- Safety [ Time Frame: Baseline (week 0), Weeks 1-9, End of trial (Week 10) ] [ Designated as safety issue: Yes ]Medical and psychiatric evaluation
- Smoking cessation [ Time Frame: End of trial (Week 10) ] [ Designated as safety issue: No ]Medical and psychiatric evaluation
|Study Start Date:||November 2009|
|Study Completion Date:||June 2011|
|Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
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.
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;
- Varenicline will be superior to placebo for smoking cessation outcomes.
- Varenicline will be well-tolerated and safe for use in Bipolar I smokers in comparison to placebo.
- Varenicline will reduce smoking indices (Carbon monoxide, cotinine) and have minimal effects on psychiatric symptomatology in mood-stabilizer treated Bipolar I smoking patients.
- The presence of prefrontal cortical, impulsivity and attentional deficits on the baseline neuropsychological battery will predict smoking cessation treatment failure in Bipolar I smokers.
- 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.
|Centre for Addiction and Mental Health|
|Toronto, Ontario, Canada, M5S 2S1|
|Principal Investigator:||Tony P George, MD||Centre for Addiction and Mental Health|