Please select the eligibility criteria that correspond to the clinical trial below.
Title: Varenicline Treatment for Smoking Cessation in Patients With Bipolar Disorder
Brief Summary: The investigators' hypothesis is that add-on varenicline will be effective (versus placebo) in initiating abstinence from smoking in subjects with stable, euthymic bipolar disorder who are motivated to quit smoking within four weeks. This primary outcome will be assessed from randomization to 12 weeks or end of the treatment phase of the study. Secondarily, the investigators also hypothesize that varenicline will prevent relapse in the subsequent 12-weeks follow-up non-treatment phase. Furthermore, the investigators plan to test the effectiveness of varenicline in reducing nicotine withdrawal symptoms or urges to smoke, as well as its safety for use in stable bipolar patients when used as an add-on treatment for smoking cessation.

The investigators plan to test these hypotheses by conducting a randomized, placebo-controlled add-on treatment trial of Chantix with 60 recruited subjects diagnosed with DSM-IV bipolar disorder for a period of three months. The investigators will follow-up with them three months later to evaluate extended abstinence.


Options:
A: Exclusion Criteria:

* Pregnant or nursing women, or women of child-bearing potential who are not using an adequate method of contraception
* Psychiatric illnesses requiring psychotropic medications (i.e., psychosis, major depression, mania), or the presence of suicidality or homocidality
* Current use of nicotine replacement therapies (i.e., nicotine patch, gum, or lozenges, nasal spray, or inhaler), bupropion (Zyban, Wellbutrin), or marijuana or current participation in another smoking cessation treatment
* Presence of unstable medical conditions (i.e., cardiac, hepatic, renal disease, diabetes mellitus) that would make a trial of bupropion SR hazardous
* Have taken monoamine oxidase inhibitors or metoprolol succinate within the past six weeks
* History of anorexia nervosa or bulimia
* Previous hypersensitivity to bupropion
* History of alcohol or other drug dependence in the past one year
* History of seizure disorder of any etiology (i.e., brain tumor, traumatic brain injury, substance-induced seizures, etc.)
* Any finding that in the view of the principal investigator would compromise the subject's ability to fulfill the protocol visit schedule and visit requirements or put the subject at risk
* Sharing home or work environment with current or past participant
* No couples or participants who see each other every day
B: Inclusion Criteria:

1. Age: 18-65 years old
2. Smoking: \>/= 5 cigarettes per day within the 2 months preceding the screening visit and expired CO greater than or equal to 6 ppm.
3. Able to follow verbal and written instructions in English and complete all aspects of the study
4. Have an address and home telephone number where they may be reached
5. Provide informed consent and agree to all assessments and study procedures
6. Be the only participant in their household

Exclusion Criteria:

1. Within the month immediately preceding the screening visit; use of any form of tobacco product other than cigarettes on 3 or more days within a week only if the individual refuses to refrain from non-cigarette tobacco use during the course of this study
2. Within the month immediately preceding the screening visit; use of marijuana in any form on 3 or more days within a week
3. Within the two weeks immediately preceding the screening visit, involvement on more than 3 days in any formal smoking cessation activities
4. Current visual or auditory problems that in the opinion of the investigator would interfere with the completion of study assessments
5. Treatment on a continuous basis within 2 weeks before the screening visit: any contraindicated medication for Varenicline or Bupropion.
6. Uncontrolled hypertension or other major contraindications for Bupropion or Varenicline.
7. Severe renal impairment (CR Clearance \<30 ml/min/1.73 m2).
8. Laboratory evaluations outside normal limits and of potential clinical significance in the opinion of the investigator
9. Meet current criteria for psychiatric disorders or substance abuse as assessed by the MINI for items A, B, D, I, J, K, L, M and N, including a past manic or hypomanic episode as well as a lifetime psychotic disorder.
10. Subject rated as moderate to high on suicidality as assessed by the MINI.
11. Psychiatric hospitalization within 1 year of screening date.
12. A positive urine pregnancy test during the screening period. Women who are two years post menopausal, one year post-tubal ligation, or who have had a partial or full hysterectomy will not be subject to a urine pregnancy test.
13. Pregnant, breast-feeding, or of childbearing potential who is not protected by a medically acceptable, effective method of birth control while enrolled in the study
14. Use of Varenicline or Bupropion within two weeks before the screening visit.
15. History of hypersensitivity or allergic reaction to Varenicline, tricyclic antidepressant, Bupropion (Wellbutrin, Zyban) or similar chemical classes or any component of these formulations.
16. Subject considered by the investigator as unsuitable candidate for receipt of an investigational drug, or unstable to be followed up throughout the entire duration of the study.
C: Subject inclusion criteria

1. DSM IV-TR Bipolar I or II or Bipolar NOS Disorder
2. Ability to provide written informed consent
3. Male or Female patients, all races, ages 18 to 65 years inclusive
4. 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.
5. MADRS total scores ≤ 8 (past 4 weeks) (suicidal item, score ≤ 1, past 4 weeks).
6. Y-MRS scores ≤ 8 (past 4 weeks) irritability, speech content, disruptive, or aggressive behavior items score ≤ 3, past 4 weeks)
7. Stable doses of primary bipolar maintenance medication for at least 8 weeks prior to randomization
8. No psychiatric hospitalization or Emergency Room Visits for psychiatric issues in the 6-month period prior to randomization
9. No suicidal attempts or behavior history past 6 months
10. No aggressive or violent acts or behavior by history past 6 months

Subject exclusion criteria

1. Uncontrolled seizure disorders and other neurological disorders including Huntington's Chorea, Multiple Sclerosis, Cerebral Palsy, and stroke (cerebrovascular accident, CVA).
2. 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.
3. Female patients who are pregnant, lactating or likely to become pregnant in next 6 months
4. 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.
5. Severe dizziness or fainting due to orthostatic blood pressure changes
6. Known hypersensitivity to varenicline
7. Current use of cimetidine
8. Current treatment with heparin, warfarin, or lidocaine
9. Comorbid psychiatric condition diagnosed within the last three months.

Subject smoking inclusion criteria

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

1. be male or female, 18 years of age or older
2. be able to understand the study, and having understood, provide written informed consent in English
3. have been enrolled in the University of Cincinnati Physicians Company-Opioid Treatment Program (UCPC-OTP) program for at least 30 days and be stable on the current methadone dose for at least 1 week
4. have smoked cigarettes for at least 3 months, have a measured exhaled carbon monoxide (CO) level \> 8 parts per million (ppm), and not planning to seek smoking-cessation treatment within the next 3 months
5. have a willingness to comply with all study procedures, including trying to stop smoking during designated weeks, and to comply with medication instructions
6. based on a week of Quitbit cigarette lighter assessments, with at least 5 days of usable data, smoke ≥ 10 cigarettes/day and smoke at least 30% of daily cigarettes within the 4-hour post-methadone-dosing period
7. if female and of child bearing potential, agree to use one of the following methods of birth control: oral contraceptives, contraceptive patch, barrier (diaphragm or condom), intrauterine contraceptive system, levonorgestrel implant, medroxyprogesterone acetate contraceptive injection,complete abstinence from sexual intercourse, hormonal vaginal contraceptive ring.

Exclusion Criteria:

1. have a current or past diagnosis of any psychotic disorder, or bipolar I or II disorder
2. have a psychiatric condition that, in the judgment of the study physician would make study participation unsafe or which would make treatment compliance difficult
3. be a significant suicidal/homicidal risk
4. have a medical condition that, in the judgment of the study physician, would make study participation unsafe or which would make treatment compliance difficult. Such conditions include, but are not limited to:

   * liver function tests greater than 3 times upper limit of normal
   * serum creatinine greater than 2 mg/dL
5. have had clinically significant cardiovascular or cerebrovascular disease within the past 6 months or have clinically significant ECG abnormalities
6. have taken an investigational drug within 30 days before consent
7. be taking concomitant medications that are contraindicated for use with the NNS or varenicline
8. be taking any concomitant medications that could increase the likelihood of smoking cessation (such as wellbutrin or nortriptyline)
9. have a known or suspected hypersensitivity to varenicline or the nicotine nasal spray (NNS)
10. use/have used smoking-cessation counseling programs with individual counseling or smoking-cessation medication treatments currently, or within 30 days before consent
11. have used electronic cigarettes or tobacco products, other than cigarettes, in the week before consent
12. be pregnant or breastfeeding
13. be anyone who, in the judgment of the investigator, would not be expected to complete the study protocol (e.g., due to relocation from the clinic area, probable incarceration, etc.)

Answer: C