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:

* Subjects will be current cigarette smokers who have smoked an average of at least 10 cigarettes per day during the past year and during the month prior to the screening visit.
* mild to moderate COPD confirmed by spirometry
* Subjects must have a clinical diagnosis of COPD.

Exclusion Criteria:

* Subjects who have made a serious attempt to quit smoking in the past 3 months.
* Subjects who have been previously randomized in a study that has included varenicline.
B: 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
C: A total of 120 subjects will be recruited in the study. Subjects will be eligible to participate if they:

1. Are at least 18 years of age;
2. Smoked more than10 cigarettes/day for the past one year;
3. Willing to make a quit attempt;
4. Able to participate fully in all aspects of the study; and
5. Have been provided with, understand, and have signed the informed consent.

Individuals will be excluded from study participation if they:

1. Meet diagnostic criteria for current major depressive disorder or lifetime history of bipolar disorder or schizophrenia. Patients with mild or moderate depressive symptoms \[Beck Depression Inventory, Second Edition \&#8804; 28\], but who do not meet current diagnostic criteria for major depressive disorder, will be included;
2. Are currently (within past 30 days) using antipsychotics or antidepressants;
3. Are currently (in previous 30 days) using any treatments for tobacco dependence (i.e., behavioral therapy, nicotine replacement therapy, bupropion SR, clonidine, or nortriptyline);
4. Have used an investigational drug within the 30 days prior to enrolling in this study;
5. Have ever used an herbal product for tobacco cessation;
6. Have recent history (in the past 3 months) of alcohol abuse or dependence as assessed by the CAGE questionnaire and study investigators;
7. Have a recent history of drug abuse as assessed by the Drug Abuse Screening Test 20 (DAST-20) and physician interview;
8. Are pregnant, lactating, or of child bearing potential, likely to become pregnant during the medication phase and not willing to use a reliable form of contraception. Reliable forms of contraception include barrier (diaphragm or condom with spermicidal jelly), injections, intrauterine device \[IUD\], surgical sterilization and abstinence;
9. Have a history of any major cardiovascular events in the past 6 months including unstable angina, acute MI or coronary angioplasty;
10. Have clinically significant acute or chronic progressive or unstable neurologic, hepatic, renal, cardiovascular, respiratory or metabolic disease;
11. Are currently on medications interacting with St. John?s Wort including warfarin, antiretrovirals (particularly indinavir and nevirapine), cyclosporine and tacrolimus, digoxin, nifedipine and verapamil, theophylline, all serotonergic drugs (serotonin reuptake inhibitors, tricyclic antidepressants, tramadol, venlafaxine, tryptophan and buspirone), MAO inhibitors, oral contraceptives, anti-cancer agents including imatinib and irinotecan, migraine medications (sumatriptan and zolmitriptan), methadone, lithium, sibutramine, atorvastatin and simvastatin, midazolam, alprazolam, fexofenadine, omeprazole, and general anesthetics (fentanyl, propofol, and sevoflurane);
12. Have another household member or relative participating in the study;
13. Have a known allergy to St. John?s Wort;
14. Have a history of photosensitivity;
15. Are professional drivers or operators of heavy machinery; and
16. Are scheduled for a planned surgical procedure within five days of taking SJW.
D: Inclusion Criteria:

* smoking at least 10 cigarettes/day in the month prior to admission
* patient has been diagnosed with acute coronary syndrome (includes patients admitted for unstable angina or acute myocardial infarction), elective percutaneous coronary intervention, or coronary artery bypass surgery at any point in time
* motivated to stop smoking
* geographically available for follow-up visits (i.e., live within 1 hour of the study centre)

Exclusion Criteria:

* have been using NRT, Zyban (or Wellbutrin), and/or Champix for more than 72 hours
* have serious cardiac arrhythmias (e.g., tachycardia), vasospastic disease (e.g., Buerger's disease, Prinzmetal's variant angina)
* have severe renal impairment or are on dialysis
* unable to read and understand English
* patient is pregnant or breastfeeding or planning on becoming pregnant during the study period

Answer: B