Please select the eligibility criteria that correspond to the clinical trial below.
Title: Combination Therapy With Varenicline and Bupropion for Smoking Cessation
Brief Summary: This study provides an opportunity to combine varenicline and bupropion SR and capitalize on the potential additive benefit. The investigators hypothesize that this will further increase long-term (≥ 6 months) smoking abstinence rates.


Options:
A: Inclusion Criteria:

1. Males and females of descent between the ages of 18-65 who smokes at least 10 cigarettes/day and are seeking smoking cessation treatment.
2. Based on the medical history, physical and laboratory examination, premenopausal female subjects must consent to practice an effective form of contraception during study.
3. Following orientation by the research staff, subjects must sign written informed consent for all study procedures.

Exclusion Criteria:

1. Women who are pregnant, planning a pregnancy, or lactating.
2. Current medical problems for which TN is contraindicated including allergy to nicotine, uncontrolled hypertension, unstable angina, serious arrhythmia, heart attack or stroke within the past 6 months, liver and/or kidney failure in the last 6-months and current diabetes.
3. Current treatment of cancer or diagnosed with cancer in the past 6 months
4. Current DSM IV substance use disorders (dependence involving alcohol, cocaine, marijuana or stimulants, benzodiazepines).
5. Current use of TN or other forms of NRT.
6. Concomitant medications (e.g., monoamine oxidase inhibitors or benzodiazepines within past 14 days, antipsychotics, endogenous steroids, and antidepressants (including wellbutrin or bupropion).
B: Inclusion Criteria:

* Age 18-75 years old
* Reports smoking at least 10 cigarettes per day AND provides a urine sample that tests positive for nicotine metabolites at intake
* Contemplating a smoking cessation attempt in the near future
* Willing to engage in a practice quit attempt during which they will be asked to smoke on one occasion
* Able to give informed consent

Exclusion Criteria:

* Currently meets Diagnostic and Statistical Manual (DSM-IV) criteria for depression, bi-polar disorder, or schizophrenia
* History of attempted suicide or expresses any current suicidal ideation
* Pregnant, breast feeding, or planning to become pregnant within the next 3 months
* Reports desire for immediate treatment of tobacco/nicotine dependence
* Severe impairment of renal function indicated by Glomerular Filtration Rate (GFR) less than 30 ml/min calculated using the Cockcroft and Gault prediction method (plasma creatinine adjusted by weight, gender, and age)
C: Inclusion Criteria:

* Age 18 years or older
* English speaking
* Smoked at least 100 cigarettes/lifetime
* Smoke 5 or more cigarettes per day
* Interested in quitting smoking (preparation or contemplation stage of change)
* Enrolled in Einstein/Montefiore methadone program for 12 weeks or more
* Receiving methadone in clinic three, four, five or six times per week
* No more than 2 methadone clinic misses in prior 14 days
* Agree to use contraception for the duration of the trial (among women with reproductive potential)
* Willing to participate in all study components
* Able to provide informed consent

Exclusion Criteria:

* Serious or unstable HIV/AIDS, liver, cardiovascular, or pulmonary disease
* Psychiatric instability
* Women who are pregnant, breastfeeding, or contemplating pregnancy
* Creatinine clearance \<30 mL/min
D: Inclusion Criteria:

1. Subject is at least 18 years of age;
2. Subject has provide written informed consent;
3. Subject is smoking greater than or equal to 10 cigarettes per day for at least 6 months;

3) Subject is able to complete all study visits 4) Subject is in good health as determined by the investigator 5) Subject has the ability to participate fully in all aspects of the study and keep scheduled appointments 6) Subject is motivated to stop smoking.

Exclusion Criteria:

Female and were pregnant, lactating or likely to become pregnant during the trial and not able nor willing to use contraception or had:

1. an unstable medical condition;
2. another household member participating in the study;
3. bupropion or varenicline allergy;
4. current use (previous 30 days) of a tobacco dependence treatment and unable or unwilling to discontinue use;
5. an unstable medical condition or unstable angina, myocardial infarction, or coronary angioplasty (past 3 months) or an untreated cardiac dysrhythmia;
6. a history of renal failure or were on renal dialysis;
7. a history of seizures;
8. as defined by the C-SSRS (Columbia-Suicide Severity Rating Scale), current non-specific suicidal thoughts or lifetime history of a suicidal attempt (defined as "potentially self-injurious act committed with at least some wish to die, as a result of act");
9. a history of closed head trauma associated with \> 30 minutes of loss of consciousness, amnesia, skull fracture, subdural hematoma, or brain contusion;
10. a history or psychosis, bipolar disorder, bulimia or anorexia nervosa;
11. current moderate or severe depression as assessed by a score of ≥ 20 on the Beck Depression Inventory, Second Edition (BDI-II) 10;
12. active substance abuse other than nicotine;
13. current (past 14 days) use of an antipsychotic, monoamine oxidase inhibitors, or drugs known to interact with bupropion SR;
14. a recent dose change of their antidepressant (within last 3 months);
15. untreated hypertension or baseline systolic blood pressure \> 180 or diastolic \> 100;
16. current treatment with another investigational drug for tobacco dependence (previous 30 days); or
17. current use of bupropion or varenicline (previous 30 days).

Answer: D