Aim 1. To assess the feasibility and acceptability of varenicline among bipolar depressed smokers as determined by our recruitment and retention rates.

Hypothesis 1. The abstinence rate for bipolar depressed patients will be 50%. The retention rate for this study will be similar to the Gonzales 2006 study (approximately 75)%.

Aim 2. To estimate the 7-day point prevalence abstinence rate at week 12, with open-label varenicline and behavioral intervention among patients with bipolar depression (N=15 with major depression, N=15 with subsyndromal or depressive symptoms). The investigators primary outcome measure is 7-day point prevalence abstinence rate defined by self-report at week 12 confirmed by expired carbon monoxide levels of 10 ppm or less.

Hypothesis 2:At final visit, approximately 50% of study completers will meet the primary outcome measure. At study entry, bipolar patients with a major depressive episode, in comparison to subjects with depressive symptoms (i.e. not syndromal episode, less severe) , will have lower abstinence rates.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).

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
• Currently on mood stabilization treatment a minimum daily therapeutic dosage of at least one mood stabilizer [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. 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).
• Agree to identify collateral individuals for contact purposes to facilitate follow-up appointments

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 the MontgomeryAsberg Depression Scale (MADRS) question #10 > 4) or any screening question on the Scale for Suicide Ideation answered affirmatively (i.e. active desire to die or commit suicide).
• History of medically serious suicide attempt.
• 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)
• 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