Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 4, Randomized, Double-blind, Active And Placebo-controlled, Multicenter Study Evaluating The Neuropsychiatric Safety And Efficacy Of 12 Weeks Varenicline Tartrate 1mg Bid And Bupropion Hydrochloride 150mg Bid For Smoking Cessation In Subjects With And Without A History Of Psychiatric Disorders
Brief Summary: This study is being conducted to assess varenicline and bupropion as aids to smoking cessation treatment in subjects with and without an established diagnosis of major psychiatric disorder and to characterize the neuropsychiatric safety profile (pre-specified adverse events (AEs) in both of these populations).


Options:
A: Inclusion Criteria:

* Male or female cigarette smokers, 18- 75 years, motivated to stop smoking and considered suitable for a smoking cessation attempt.
* Smoked an average of at least 10 cigarettes per day during past year and during the month prior to the screening visit, and exhaled carbon monoxide (CO) \>10 ppm at screening.
* For Neuropsychiatric cohort- subjects must have proper diagnosis as outlined in protocol.

Exclusion Criteria:

* Subjects with a past or current diagnosis of one of the following disorders:

  a. Psychotic Disorders:
* Schizophreniform
* Delusional Disorder
* Psychotic Disorder NOS b. All Delirium, Dementia, and Amnestic and Other Cognitive Disorders c. All Substance Induced Disorders (Other than nicotine)
B: 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.
C: DISEASE CHARACTERISTICS:

* African American who has smoked ≤ 10 cigarettes per day for ≥ 2 years AND has smoked for ≥ 25 days within the past month

  * Not a heavy smoker
  * No other forms of tobacco within the past 30 days
* Must be interested in stopping smoking
* No other smoker in the household enrolled in this study

PATIENT CHARACTERISTICS:

* Has a home address and a functioning telephone number
* Not planning to move from the Kansas City metro area within the next 12 months
* Not pregnant or nursing
* Negative pregnancy test
* No alcohol or substance abuse within the past year
* Not currently drinking ≥ 14 alcoholic drinks per week
* No binge drinking (5 or more drinks on one occasion) on at least two occasions within the past month
* No history of seizures or head trauma
* No history of bulimia or anorexia nervosa
* No myocardial infarction within the past 30 days
* No reported use of opiates, cocaine, or stimulants
* No diabetes requiring oral hypoglycemics or insulin

PRIOR CONCURRENT THERAPY:

* More than 30 days since prior nicotine replacement therapy, fluoxetine, clonidine, buspirone, or doxepin
* No other concurrent medication that contains bupropion hydrochloride
* No concurrent psychoactive medications
D: Inclusion Criteria:

* 18-65 years old;
* Smoke an average of at least 10 cigarettes per day;
* Have smoked at least one cumulative year;
* Have an expired air CO reading of at least 10ppm;
* Body weight of \>50 kg (110 lbs.)
* Able to read and understand English;
* Express a desire to quit smoking in the next thirty days.

Exclusion Criteria:

* Hypertension (systolic \>140 mm Hg, diastolic \>100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100.
* Hypotension with symptoms (systolic \<90 mm Hg, diastolic \<60 mm Hg).
* Participants with a history of hypertension may, however, be allowed to participate in the study if the study physician or physician assistant determines that the condition is stable, controlled by medication, and in no way jeopardizes the individual's safety.
* Coronary heart disease, diagnosed by coronary angiogram;
* Lifetime history of heart attack;
* Cardiac rhythm disorder (irregular heart rhythm);
* Chest pain in the last month (unless history, exam, and ECG clearly indicate a non-cardiac source);
* Symptomatic cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure);
* Diagnosis of liver disease or kidney disorder (except kidney stones, gallstones);
* Gastrointestinal problems (e.g. Celiac disease, Crohn's dx Ulcerative Colitis) or disease other than gastroesophageal reflux or heartburn;
* Active ulcers in the past 30 days;
* Currently symptomatic lung disorder/disease (including but not limited to chronic obstructive pulmonary disease (COPD), emphysema, and asthma);
* Brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder);
* Migraine headaches that occur more frequently than once per week;
* Recent, unexplained fainting spells;
* Problems giving blood samples;
* Diabetes (unless controlled by diet and exercise alone and screening glucose is less than 180mg/dcl and HbA1c is less than 7%);
* Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer);
* HIV, Hepatitis B, or Hepatitis C
* History of tuberculosis or recent positive purified protein derivative (PPD) test
* Other major medical condition;
* Current psychiatric disease (with the exception of anxiety disorders, obsessive compulsive disorder (OCD) and ADHD);
* Suicidal ideating (thinking about ways to commit suicide) (within the past 10 years) or lifetime occurrence of attempted suicide;
* Current depression - The Patient Health Questionnaire (PHQ-9) for Depression will be used to screen for current (within 2 weeks) depression. Potential subjects who score \>9 (or who score \>0 on item #9 ("Thoughts that you would be better off dead, or of hurting yourself in some way") will be excluded from study participation, and, at the discretion of the study physician, referred to appropriate psychiatric treatment;
* Bulimia or anorexia;
* BMI of \< 18.5 kg/m2;
* Prior use of fenfluramine or dexfenfluramine
* Use (within the past 30 days) of:

  * Illegal drugs (or if the urine drug screen is positive for tetrahydrocannabinol (THC), Cocaine, Amphetamine, Opiates, Methamphetamines, phencyclidine (PCP), Benzodiazepines, or Barbiturates), Unless recent use of prescription Opiates, Benzodiazepines for management of acute symptoms.
  * Experimental (investigational) drugs;
  * Psychiatric medications including antidepressants (selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), St. John's Wort), lithium, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine);
  * Phentermine, triptans, tryptophan, linezolid, dextromethorphan, opiates, tramadol, or dopamine agonists;
  * Any agents that have documented correlation with increased incidence of valvulopathy and/or pulmonary hypertension (e.g., cyproheptadine, trazodone, nefazodone, amoxapine, tricyclic antidepressants, mirtazapine, pergolide, ergotamine, methysergide) (or anticipated use during the study);
  * Smokeless tobacco (chewing tobacco, snuff), pipes or e-cigarettes;
  * Wellbutrin, bupropion, Zyban, Chantix, varenicline, nicotine patch, nicotine replacement therapy or any other smoking cessation aid.
* Concurrent use of a serotonergic agent/combination associated with severe serotonin syndrome (within the past 30 days);
* Use of cigar, cigarillos, pipe, Hookah, dissolvable nicotine, snuff, chewing tobacco more than once per month.
* Use of e-cigarettes once per month or more.
* Self-report of consuming 4 or more alcoholic drinks on 1 or more days per week;
* Significant adverse reaction to lorcaserin or nicotine patch in the past.
* Current participation or recent participation (in the past 30 days) in another smoking study at the investigators Center or another research facility.
* Current participation in another research study.

Answer: A