Varenicline Treatment for Smoking Cessation in Patients With Bipolar Disorder

Subject inclusion criteria

• DSM IV-TR Bipolar I or II or Bipolar NOS Disorder
• Ability to provide written informed consent
• Male or Female patients, all races, ages 18 to 65 years inclusive
• Negative serum pregnancy test for females of child-bearing potential. Patients must agree to one of the following birth control methods: an oral contraceptive agent, an intrauterine device (IUD), an implantable contraceptive (e.g., Norplant), or an injectable contraceptive (e.g., Depo Provera) for at least 1 month prior to entering the study and will continue its use through at least 30 days after the last dose of study medication or a barrier method of contraception, e.g., condom and/or diaphragm with spermicide while participating in the study through at least 30 days after the last dose of study medication or abstinence.
• MADRS total scores ≤ 8 (past 4 weeks) (suicidal item, score ≤ 1, past 4 weeks).
• Y-MRS scores ≤ 8 (past 4 weeks) irritability, speech content, disruptive, or aggressive behavior items score ≤ 3, past 4 weeks)
• Stable doses of primary bipolar maintenance medication for at least 8 weeks prior to randomization
• No psychiatric hospitalization or Emergency Room Visits for psychiatric issues in the 6-month period prior to randomization
• No suicidal attempts or behavior history past 6 months
• No aggressive or violent acts or behavior by history past 6 months

Subject exclusion criteria

• Uncontrolled seizure disorders and other neurological disorders including Huntington's Chorea, Multiple Sclerosis, Cerebral Palsy, and stroke (cerebrovascular accident, CVA).
• Current alcohol or other substance abuse or dependence within the last 3 months (caffeine will be permitted, nicotine dependence is part of inclusion criteria), including a case-by-case evaluation of those who meet remission criteria and who are on long-term substance abuse and/or alcohol abuse treatment.
• Female patients who are pregnant, lactating or likely to become pregnant in next 6 months
• Uncontrolled diabetes mellitus, asthma, seizure disorder, uncontrolled hypertension, (uncontrolled hypertension is defined as Systolic BP > 150 mm or Hg or diastolic BP > 95 mm or Hg on 2 consecutive BP readings 15 minutes apart at the time of screening) or unstable medical illness. Moderate to severe renal disease - moderate renal failure is defined as serum Creatinine >1.3 mg/dl in women and > 1.5 mg/dl in men, at the time of screening.
• Severe dizziness or fainting due to orthostatic blood pressure changes
• Known hypersensitivity to varenicline
• Current use of cimetidine
• Current treatment with heparin, warfarin, or lidocaine
• Comorbid psychiatric condition diagnosed within the last three months.

Subject smoking inclusion criteria

• Score of 7 or greater on the Contemplation Ladder, and willing to pick a target quit date within the next 4 weeks.
• Smoke > 10 cigarettes per day.
• Expired breath CO level > 10 ppm at screening and randomization.
• No use of smoking cessation medication and/or behavioral treatment for smoking cessation in the past three months.
• No current use of any nicotine replacement treatment.
• Not using any tobacco products other than cigarettes.
• No current treatment for smoking cessation (hypnosis, acupuncture, others).
• No current use or past treatment failure with varenicline.
• No current treatment with bupropion for smoking cessation.