Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effects of a Tailored Dose of Varenicline on Post-quitting Urges to Smoke
Brief Summary: Varenicline is a partial nicotinic agonist which acts on alpha4 beta2 nicotinic receptors. It is presumed to alleviate withdrawal discomfort, but also to diminish rewarding effects of cigarettes. The standard varenicline dosing has been formulated to avoid adverse reactions (primarily nausea) in sensitive clients. The downside of this cautious approach is that a substantial proportion of clients may be under-dosed. A blanket dose increase would inevitably increase the incidence of side effects, but it is likely that tailoring varenicline dosing to clients' needs would be safe and may further increase varenicline's efficacy.

This study will recruit 200 smokers who report little change to their enjoyment of cigarettes and no nausea, during the first week of varenicline use. These smokers will be randomised to receive the standard dose plus placebo or plus individualised varenicline dose up to 5mg, titrated over the next week prior to their target quit day. Urges to smoke, and other withdrawal symptoms, experienced during the study period will be compared between groups to see if the tailored therapy may be useful.


Options:
A: 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
B: Inclusion Criteria:

1. 18 years of age and older;
2. diagnosis of HIV;
3. self-reported smoking on a daily basis;
4. provide informed written consent

Exclusion Criteria:

1. persons with active psychosis or impaired mental status as judged by the clinic staff and confirmed with a Mini-Mental Status Exam)
2. unable to understand spoken English
3. age less than 18 years.
4. pregnant women
C: Inclusion Criteria:

1. Has signed the ICF and is able to read and understand the information provided in the ICF.
2. Is 21 to 65 years of age (inclusive) at screening.
3. Smokes at least 10 commercially available cigarettes per day (no brand restrictions), for the last 12 months.
4. Has an expired air CO reading of at least 10 ppm at screening.
5. Is interested in switching to an electronic cigarette.
6. Is willing and able to comply with the requirements of the study.
7. Owns a smartphone with text message and data capabilities compatible with necessary surveys.

Exclusion Criteria:

1. Is unhealthy or cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason) as judged by the Investigator or designated medical staff based on all available assessments from the screening period (e.g., safety laboratory, vital signs, physical examination, ECG, concomitant medications and medical history).
2. Has a PHQ-9 score greater than 9, or a score greater than 0 on item #9 ("Thoughts that you would be better off dead, or of hurting yourself in some way") at screening.
3. Has plans to use an FDA-approved smoking cessation product during the study.
4. Has high blood pressure (systolic \> 150 mmHg or diastolic \>95 mmHg) at screening.
5. Has body mass index (BMI) less than 15.0 kg/m2 or greater than 40.0 kg/m2.
6. Has coronary heart disease, structural cardiac disease (including, but not limited to valvular heart disease or cardiac murmurs), cardiac dysrhythmias, syncope, cardiac chest pain, or history of heart attack or heart failure.
7. Has received psychotherapy or behavioral treatments potentially impacting symptoms of depression, anxiety, or nicotine withdrawal within 30 days of screening, or during the study.
8. Is taking antidepressants, psychoactive medications (e.g. antipsychotics, benzodiazepines, hypnotics) or medications that prolong QTc.
9. Has used any of these products in the past 30 days:

   1. Illegal drugs (or if the urine drug screen is positive for cocaine, THC, amphetamines, methamphetamines, or opiates);
   2. Experimental (investigational) drugs that are unknown to participant;
   3. Chronic opiate use.
10. Has used smokeless tobacco (chewing tobacco, snuff), cigars (except for "Black \& Mild" cigars or Cigarillos), pipes, hookah, e-cigarettes, nicotine replacement therapy or other smoking cessation treatments within 14 days of screening.
11. Has a plan to use an FDA-approved quit-smoking treatment in the next 30 days.
12. Is pregnant or nursing (by self-report) or has a positive pregnancy test.
13. Enrollment requirements met.
D: Inclusion Criteria:

* Smoker seeking treatment
* Aged 18 and over
* Consenting to take part
* Report little or no change in enjoyment of cigarettes and/or nausea

Exclusion Criteria:

* Pregnant or breastfeeding
* Have severe kidney disease
* Have severe heart problems
* Have a current psychiatric illness
* Are unable to fill in questionnaires in English
* Have an allergy to varenicline
* Are currently involved in another clinical trial

Answer: D