Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 10-Week Pilot Study of Varenicline (Champix) Versus Placebo for Smoking Cessation/Reduction in Patients With Bipolar Disorder
Brief Summary: Bipolar Disorder is a chronic relapsing mental disorder characterized by periods of elevated, expansive and irritable mood, often alternating with periods of significant clinical depression. People with Bipolar Disorder are typically heavy smokers who have difficulty quitting, and this is associated with significant tobacco-related medical illness and death.

The proposed study will be a double-blind, placebo-controlled 10-week clinical trial of the safety and efficacy of varenicline (Champix™) in thirty subjects with Bipolar I Disorder. This medication is the latest first-line pharmacotherapy for smoking cessation and has been shown to be efficacious for smoking cessation, but has not yet been systematically studied in persons with Bipolar Disorder.


Options:
A: Inclusion Criteria:

Subjects will be eligible to participate if they:

1. Are at least 18 years of age
2. Have used ST daily for the past 12 months (regular user)
3. Identify ST as their primary tobacco product
4. Are in general good health (determined by medical history and screening physical examination)
5. Has provided written informed consent to participate
6. Are able to participate in all aspects of the study

Exclusion Criteria:

Individuals will be excluded from study participation if they:

1. Are currently (in previous 30 days) using other behavioral or pharmacologic tobacco cessation programs (i.e., behavioral therapy, nicotine replacement therapy, clonidine, bupropion SR, or doxepin)
2. Have self-reported current, untreated depression or a Beck Depression Inventory (BDI-II) Score of ≥ 20
3. Have, as defined by the C-SSRS (Columbia-Suicide Severity Rating Scale);current non-specific suicidal thoughts, or have a 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.")
4. History of psychosis or bipolar disorder
5. Are currently pregnant or lactating or is of childbearing potential and not willing to use any form of contraception
6. Have another member of their household already participating in this study
7. Are allergic to varenicline
8. Describe having a medical history of:

   * Unstable angina
   * Myocardial infarction within the past 3 months
   * Cardiac dysrhythmia other than medication-controlled atrial fibrillation or PSVT
   * Medically-treated or untreated hypertension with BP ≥ 200 systolic OR ≥ 100 diastolic
   * Have other medical or psychiatric conditions that would exclude the participant
B: Inclusion Criteria:

* Eligible participants will be 68 (34 male and 34 female) smokers aged 18-65, who smoke ≥ 10 cigarettes per day, provide a baseline CO reading ≥ 10 ppm and who plan to live in the area for the next 6-months.

Exclusion Criteria:

* Smoking Behavior

  1. Use of chewing tobacco or snuff
  2. Current enrollment or plans to enroll in another smoking cessation program in the next 5 months
  3. Plan to use other nicotine substitutes or smoking cessation treatments in the next 5 months
  4. Provide a baseline CO reading \< 10 ppm

Alcohol/Drug Exclusion Criteria

1. History of substance abuse and/or currently receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, or stimulants)
2. Current alcohol consumption that exceeds \>25 standard drinks/week

Medication Exclusion Criteria

1. Current use or recent discontinuation (within last 14-days) of the following medications:

1. Any form of smoking cessation medication (zyban, wellbutrin, wellbutrin SR, Chantix, NRT)
2. Any form of anti-psychotic medications that includes:

   * antipsychotics,
   * atypical antipsychotics,
   * mood-stabilizers,
   * anti-depressants (tricyclics, SSRI's, MAOI's),
   * anti-panic agents,
   * anti-obsessive agents,
   * anti-anxiety agents, and
   * stimulants (e.g., Provigil, Ritalin).
3. Medication for chronic pain
4. Anti-coagulants
5. Any heart medications
6. Daily medication for asthma

Medical Exclusion Criteria

1. Women who are pregnant, planning a pregnancy, or lactating.
2. History or current diagnosis of psychosis, major depression or bipolar disorder, schizophrenia, or any Axis 1 disorder as identified by the SCID.
3. Serious or unstable disease within the past 6 months (e.g., cancer \[except melanoma\], heart disease, HIV).
4. History of epilepsy or a seizure disorder.
5. History or current diagnosis (last 6-months) of abnormal rhythms and/or tachycardia (\>100 beats/minute); history or current diagnosis of COPD, cardiovascular disease (stroke, angina, coronary heart disease), heart attack in the last 6 months, uncontrolled hypertension (SBP\>150 or DBP\>90)
6. History of Kidney and/or liver failure (including transplant).
7. Wears a device to aid in hearing (hearing aid, cochlear implant, etc.).
8. Hearing threshold \< 40 dB SPL at 1000 Hz.
9. Color blindness.

General Exclusion

1. Any medical condition or concomitant medication that could compromise participant safety or treatment, as determined by the Principal Investigator and/or Study Physician.
2. Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.
3. Any physical or visual impairment that may prevent the individual from using a computer keyboard or completing any study tasks.
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:

* Structured Clinical Interview (SCID) derived DSM-IV diagnoses of Bipolar Disorder (Type I or II), and Nicotine Dependence
* Young Mania Rating Scale Total Score \<12 at study entry
* HAM-D 17-Item Score \>5 and \<24 at study entry
* Fagerstrom Test for Nicotine Dependence (FTND) score of 5 or higher
* Be able to provide informed consent to participate in this study as judged by clinical evaluation, and scoring at least 80% on a post-consent "test"
* Smoking at least 10 cigarettes per day (confirmed by an expired breath CO level \>10 ppm and a plasma cotinine level \>150 ng/ml at baseline)
* Be motivated to quit smoking within 30 days of initial evaluation, as assessed by a score of 7 or higher on the Contemplation Ladder assessment tool
* On a stable dose of a mood stabilizer for at least 1 month (e.g. lithium, valproate, carbamazepine, atypical antipsychotic)
* Judged by the study psychiatrists and/or trained psychiatric clinicians to be in remission from active manic, hypomanic, major depressive and psychotic symptoms based on a clinical interview and SCID-IV ≥1 month prior to study enrollment

Exclusion Criteria:

* Meet criteria for current abuse or dependence for any other alcohol or illicit substance within the past 3 months of study enrollment
* Current evidence by SCID-IV and clinical evaluation of suicidality, homicidality or psychosis
* Meet DSM-IV criteria for current major depression at the time of baseline evaluation
* A history of hypersensitivity or other known adverse reactions (e.g. hyperstimulation, severe agitation) to varenicline.
* Serious medical conditions (i.e. a history of severe cardiac, renal or hepatic disease, diabetes mellitus or thyroid abnormalities)
* EKG abnormalities
* Prescription of Nicotine Replacement Therapies (NRTs) including patches, gum, lozenges or inhalers
* Prescription of monoamine oxidase inhibitors (MAO-I's) including selegiline or moclobemide
* Prescription of varenicline
* Prescription of bupropion SR
* The presence of manic, mixed manic or hypomanic symptoms in the past one month prior to study enrollment.
* A lifetime history of antidepressant-induced mania or hypomania
* A history of suicidal ideation while taking antidepressants

Answer: D