Varenicline in Bipolar Depressed Patients

Study Overview
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Brief Summary
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Patients with bipolar disorder have one of the highest rates of nicotine dependence and one of the lowest quit rates. Varenicline has been shown in previous trials to be effective for smoking cessation, but has not been studied in subjects with bipolar disorder. This 12-week open label trial will be conducted to assess the feasibility, acceptability, and safety of varenicline in bipolar depressed smokers, given in addition to the subject's primary treatment for bipolar disorder. The primary study hypothesis was that the abstinence rate for bipolar depressed patients will be 50%.

Detailed Description
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Varenicline, a nicotinic acetylcholine receptor partial agonist, has been shown in two placebo-controlled trials to be efficacious for smoking cessation. Given the high prevalence of nicotine dependence in bipolar disorder and the high prevalence of sub-syndromal and syndromal depressive symptoms in bipolar disorder, this 12-week adjunctive varenicline open label trial will be conducted to assess the feasibility, acceptability, and safety of varenicline in bipolar depressed smokers. All subjects will receive individual behavioral counseling. Primary hypothesis: the abstinence rate for bipolar depressed patients will be 50%. Secondary hypothesis: At final visit, bipolar depressed patients who have achieved remission, defined as a Montgomery Asberg Depression Rating Scale (MADRS) <8, will have a higher rate of tobacco abstinence than depressed patients who did not achieve remission (MADRS >/= 8).

Official Title
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Varenicline for Smoking Cessation in Bipolar Depressed Patients: An Open-Label 12-week Feasibility Trial

Conditions
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Smoking, Bipolar Disorder, Depression

Intervention / Treatment
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* Drug: Varenicline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 -65 years Meet DSM-IV criteria for bipolar disorder type I or II and nicotine dependence DSM-IV confirmed current major depressive episode OR current depressive symptoms defined as MADRS > 4 & <20 Smoke at least 10 cigarettes per day Fagerström Test of Nicotine Dependence (FTND) score of 5 or higher Agree to identify collateral individuals for contact purposes to facilitate follow-up appointments Currently on mood stabilization treatment. A minimum daily therapeutic dosage of at least one mood stabilizer, and on the same dose for at least 2 weeks: Lithium (0.6-1.2 mEq/L or 900 mg), Valproate (50-125 mg/mL or 1000 mg), Carbamazepine (4-12 mg/mL or 800 mg), Oxcarbazepine 1200 mg, Lamotrigine 100 mg, Olanzapine 10mg, Risperidone 2mg, Quetiapine 300mg, Ziprasidone 40mg, Aripiprazole 7.5 mg Antidepressants are not exclusionary. Topiramate is an acceptable mood stabilization treatment. There is an evidence base (Delbello et al. 2005) highlighting efficacy of topiramate monotherapy for acute mania in children and adolescents with bipolar disorder type 1. [Mood stabilizers are a standard American Psychiatric Association (APA) treatment guidelines for Bipolar I disorder (history of mania). While the guidelines for Bipolar II disorder are unclear (history of hypomania), we feel mood stabilization provides standardization of treatment and maximizes safety (ie: preventing switch from depression to mania or hypomania).] Exclusion Criteria: DSM-IV dependence for a substance other than nicotine or caffeine within past 3 months. DSM-IV criteria of schizophrenia or other non-affective psychotic disorder Psychotic symptoms within the past month Active suicidality as measured by screening questions from the Columbia-Suicide Severity Rating Scale (C-SSRS History of medically serious suicide attempt as reviewed by doctor. Current use (past 30 days) of other smoking cessation treatments Pregnant or nursing women, or women who refuse to use adequate birth control Serious, active or unstable medical condition Individuals, in the investigators opinion, unable to comply with study procedures Inability to provide written informed consent in English Allergic reaction to varenicline Individuals who are on dialysis or have a history of kidney disease (varenicline is excreted 96% unchanged through the kidneys) or Creatine supplementation or current anticipated daily NSAID use Presence of a personality disorder, that upon review of the medical record, appears to be the primary reason for psychiatric care.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Varenicline<br>Open-label; subjects will receive a behavioral intervention in addition to Varenicline. | Drug: Varenicline<br>* Varenicline (Chantix®, Pfizer) is an oral medication with a recommended dosage of 0.5 mg once daily for 3 days, increasing to 0.5 mg twice daily for days 4-7, and then to the maintenance dose of 1 mg twice daily for the 12 weeks of treatment.<br>* Other names: Chantix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Carbon Monoxide Breath Level at 12 Weeks | Measured by expired breath in parts per million (ppm) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale (MADRS) at 12 Weeks | MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Each item on the MADRS is scaled 0 through 6. Lowest score = 0, would indicate no depressive symptoms. Highest score = 60, indicating extreme depression. MADRS score > 20 is syndromal depression. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134:382-389. | 12 weeks | 
| Young Mania Rating Scale (YMRS) at 12 Weeks | YMRS is an eleven-item, multiple choice diagnostic questionnaire which psychiatrists use to measure the severity of manic episodes in patients already diagnosed with mania. Lowest score = 0, normal subject; Highest score = 60, highly manic subject. For this scale the following scores are associated with these grades of severity: mania (YMRS = 20), hypomania (YMRS = 12), under 5 is classified as non-manic. Young RC, Biggs JT, Ziegler Ve, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. BR J Psychiatry 1978; 133:429-435. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking, Bipolar Disorder, Depression