This study will focus on enhancing future smoking cessation treatment effectiveness by piloting a potentially more powerful combination of three FDA-approved pharmacotherapies: varenicline plus combination of two types of nicotine replacement therapy (NRT) treatment (nicotine lozenge and nicotine patch). Data from this pilot study will help inform the design of future studies that would use this combination treatment as a cessation tool within the chronic care arsenal of treatments.

Recent research suggests that a new combination therapy may be especially effective in increasing long-term abstinence from smoking. A key purpose of the proposed study is to examine what types of tolerability concerns, if any, emerge from the simultaneous use of three FDA-approved cessation medications (varenicline, nicotine patch, and nicotine lozenge) and the timing of those events, in order to better assess how the use of this combination of tobacco cessation medicines can be most effectively and safely delivered and monitored. Study participants will take the three medications for 12 weeks in a manner consistent with labeling. Adverse events will be assessed at all study visits.

Inclusion Criteria:

• Age >17 years;
• >=5 cigarettes/day for the previous 6 months;
• alveolar CO >= 6 ppm; able to read, write and speak English;
• planning to remain in the intervention catchment area for at least 4 months; not currently taking bupropion or varenicline;
• if the participant is currently using NRT, s/he agrees to use only study medication for the duration of the study;
• free of medical contraindications to NRT and varenicline; and,
• if participant is a woman of childbearing potential, using an approved method of birth control during treatment.

Exclusion Criteria:

• Current diagnosis of/treatment for psychosis or bipolar disorder;
• suicidal ideation within the past 12 months; any history of suicide attempts; * significant hepatic or renal impairment; history of significant allergic reactions to varenicline or any type of NRT in the past;
• use of any investigational drugs in the previous 30 days. -

12 weeks

The AE assessment specifically queried the presence or absence of: chest tightness, angina, dizziness, dreams, insomnia, mood changes, nausea, skin rash, sweating, shortness of breath, and vomiting. The severity of each AE was graded as: mild (no interference with daily activities, no medications needed to treat symptom); moderate (some interference with daily activities, over-the-counter medications needed); severe (unable to perform daily activity, prescription medication needed).