Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Examination of the Efficacy, Safety, and Gender Differences in Using Varenicline as an Aid to Smoking Cessation in a Population of Methadone Maintained Opioid Dependent Patients (Pilot Trial)
Brief Summary: The main hypotheses guiding the study are:

1. Stable methadone maintenance patients receiving varenicline will be more likely to maintain abstinence than patients receiving placebo
2. There will be no differences in the type and number of symptoms reported between stable methadone maintenance patients receiving varenicline and placebo
3. There will be no changes in methadone dosage between abstinent and non-abstinent smokers
4. There will be no differences in efficacy, withdrawal symptoms, and safety of varenicline between male and female participants


Options:
A: Inclusion Criteria:

* Stable on methadone maintenance (an individual is considered 'stable' if they have had a 4 week constant/fixed dose of methadone by self report and verified by B.C. Pharmanet review)
* Subjects must have smoked at least 10 cigarettes per day during the past year and over the month prior to the screening visit, with no period of abstinence greater than 3 months in the past year
* Ages 19 to 75 years (inclusive) and motivated to quit smoking
* Should read and understand English
* For female subjects:

  * instructed and agrees to avoid pregnancy through 30 days after the last dose of study medication
  * has a negative urine pregnancy test at screening
  * agrees to use birth control method(s) for duration of the study
* Should be available by telephone

Exclusion Criteria:

* Subjects who have used varenicline previously or are currently on other Nicotine Replacement Therapy or pharmacotherapy for smoking cessation (e.g., nicotine patch, zyban or wellbutrin)
* Subjects who have a prior or current history of depression, bipolar affective disorder or a prior or current history of psychotic episodes or suicidal ideation (on the basis of self-report augmented by medical chart review where appropriate and/or corroborating history with previous or current health care provider)
* Subjects who have not reached a stable dose of methadone in their methadone maintenance therapy (4 weeks at a constant/fixed dose of methadone by self-report and verified by B.C. Pharmanet review)
* Pregnancy or currently nursing
B: Inclusion Criteria:

* Meets DSM-IV criteria for nicotine dependence with a Fagerstrom Test of Nicotine Dependence (FTND) score greater than 5
* Smokes at least 15 cigarettes daily (averaged over 1 week, within the month prior to enrollment)
* Motivated to quit smoking within 30 days at time of initial evaluation
* At least one unsuccessful attempt to quit smoking in the past year
* An expired breath CO level greater than 10 ppm and baseline plasma cotinine level greater than 150 ng/ml at initial evaluation
* Body weight of at least 100 lb
* Avoidance of nicotine replacement product use one month prior to enrollment
* Speaks English

Exclusion Criteria:

* Currently taking over-the-counter or prescription sympathomimetic agents (e.g., pseudoephedrine, methylphenidate), antidepressant agents (e.g., tricyclic antidepressants, serotonin reuptake inhibitors, bupropion, other monoamine oxidase inhibitors), or meperidine (Demerol)
* Serious medical disorders such as unstable angina or liver failure
* Abnormalities in baseline bloodwork (e.g., threefold elevation of liver function tests, electrolyte abnormalities)
* Physiologically dependent on and/or abusing alcohol or other drugs of abuse (e.g., cocaine, opiates, benzodiazepines, etc.) during the 6 months prior to enrollment (based on a clinical evaluation, which includes a self-report, and is confirmed by a positive urine toxicology screen)
* Meets DSM-IV criteria for a current diagnosis of major depressive disorder, panic disorder, or post-traumatic stress disorder
* Current or past history of bipolar disorder or schizophrenia
* Past history of major depression associated with historical evidence of suicidal or homicidal behavior, or psychotic symptoms
* Currently residing with another study participant
* Presence of suicidal or homicidal ideation
* Significant impairment of social or occupational functioning, either at time of initial evaluation or during the trial
* Known hypersensitivity to selegiline hydrochloride
C: Inclusion Criteria:

* Subjects must have smoked an average of at least ten cigarettes per day during the past year
* No period of abstinence greater than three months in the past year

Exclusion Criteria:

* Subjects with history of clinically significant cardiovascular disease
* Subjects with uncontrolled hypertension.
D: Inclusion Criteria:

* Subjects will be 144 smokers who have experienced at least one episode of major depressive disorder and 206 smokers who lack a lifetime history of major depressive disorder.
* None will currently meet diagnostic criteria for major depression, nor will they have met criteria in the past 6 months.
* All will be male and female community members between the ages of 18 and 65 who have smoker at least 10 cigarettes a day for the past year.

Exclusion Criteria:

Subjects may not enter the trial if they:

1. have taken monoamine oxidase inhibitors, antidepressants, anti-anxiety agents, lithium, tryptophan or phenothiazines within the past month;
2. are being treated for hypertension with guanethidine, reserpine, thiazide diuretics, beta blockers, or clonidine;
3. are taking Type IC antiarrhythmics (e.g., propafenone and flecanide) or a highly protein-bound drug (e.g., warfarin, digitoxin);
4. have a medically unstable condition or had a major health event in the past 6 months (e.g., myocardial infarct or major surgery);
5. have CBC values more than 10% outside the normal limits, or liver enzymes exceeding 40% of the upper limit of normal;
6. have a history of severe allergies, multiple adverse drug reactions or known allergy to fluoxetine;
7. are actively abusing alcohol or drugs or received inpatient treatment for substance abuse within the past year;
8. are using nicotine replacements;
9. are pregnant, lactating, or of childbearing potential;
10. present current evidence of organic brain disease, definite or subclinical major depressive disorder or serious suicidal risk post-traumatic stress disorder, or premenstrual dysphoric disorder;
11. have a score greater than 14 on the 21-item Hamilton Depression Rating Scale or greater than 15 on the Beck Depression Inventory;
12. have a history of seizures, mania or hypomania, or psychosis. Individuals with bipolar disorder, PTSD, or schizophrenia will be excluded because they might respond adversely to fluoxetine.

Subjects with dysthymic disorder or anxiety disorders will be studied if their current symptoms are not sequelae of an episode of major depression. Excluding such cases would purify the sample by removing mild degrees of dysphoria, but would greatly restrict our ability to generalize any treatment implications to the current population that smokers.

Answer: A