Please select the eligibility criteria that correspond to the clinical trial below.
Title: Testing a Full Substitution Therapy Approach As Treatment of Tobacco Dependence
Brief Summary: This study will test a new medication strategy designed to help smokers quit. It will combine selegiline, a drug currently approved and available for the treatment of Parkinson's disease, with a nicotine skin patch. Forty nicotine-dependent smokers will enrolled in this study. Twenty will receive placebo (inactive pill) plus nicotine patch, and twenty will receive selegiline plus nicotine patch. Once enrolled in the study, subjects will visit the Nicotine Dependence Clinic at CAMH on a weekly basis for assessment of smoking behavior, a brief health check, collection of breath and urine samples (necessary to drug levels and nicotine levels), and receive brief individual counseling designed to help them stop smoking. The medication phase of this study lasts 9 weeks. A follow-up visit will be conducted six months after trial completion. At that point, health and behavioral measures will be re-assessed.


Options:
A: Inclusion Criteria:

* Meet DSM-IV criteria for nicotine dependence with FTND score \> 5.
* Smoke at least 15 cigarettes (3/4 pack) daily (averaged over 1 week, in the past 1 month).
* At the time of initial evaluation, are motivated to quit smoking in the next 30 days.
* Have made at least one unsuccessful attempt to quit smoking in the past year.
* At baseline, have expired breath CO level \> 10.
* Are between ages 18-70 years old.
* Weigh at least 100 lbs (45.5 kg, selegiline dose \< 0.22 mg/kg).
* No previous use of nicotine replacement products in the one month prior to randomization.
* Have the capacity to give informed consent, and are English-speaking.

Exclusion Criteria:

* Have present or past diagnoses of schizophrenia, bipolar disorder, PTSD, BPD or major depressive illness.
* Have abused alcohol or other drugs of abuse (cocaine, opiates, benzodiazepines, etc) in 6 months prior to randomization into the trial (based on clinical evaluation including self-report, and confirmed by positive urine).
* Demonstrate serious medical conditions (i.e. abnormal liver function \[as evidenced by AST, ALT or bilirubin values 2x ULN\], unstable cardiovascular disease, significant blood abnormalities).
* Exhibit or have history of clinical hypertension.
* Exhibit active peptic ulcer disease.
* Are pregnant, are trying to become pregnant, or are currently breastfeeding.
* Are on current medication regimes that include antidepressants, or sympathomimetic agents, or meperidine and other meperidine-opioids which may have interactions with selegiline.
* Known hypersensitivity to selegiline or NRT.
* Are from the same household as another study participant.
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:

* Men and women
* 18 to 75 yrs old
* Motivated to stop smoking
* Smoke at least 10 cigarettes/day

Exclusion Criteria:

* Active psychiatric disease
* Severe or unstable cardiovascular or pulmonary disease
* Current or recent treatment to stop smoking
* Previous use of varenicline

Answer: A