Flexible and extended dosing of nicotine replacement therapy or varenicline in comparison to fixed dose nicotine replacement therapy for smoking cessation: rationale, methods and participant characteristics of the FLEX trial.

Quitting smoking is the single most effective strategy to reduce morbidity and premature mortality in smokers. Research has demonstrated the effectiveness of pharmacotherapy in smoking cessation, but few studies have directly compared varenicline and monotherapy nicotine replacement therapy (NRT) and none have examined varenicline and combinations of NRT products. The majority of smoking cessation trials involve carefully circumscribed populations, making their results less generalizable to those with severe medical conditions or psychiatric comorbidities. This paper reports on the rationale, methodology and participant characteristics of a randomized controlled trial designed to: (1) determine which pharmacotherapy - NRT, long term combinations of NRT, or varenicline - is most effective in achieving abstinence; (2) investigate the incidence of neuropsychiatric symptoms among participants over the course of their quit attempt; and (3) assess whether there is a significant difference in the incidence of neuropsychiatric symptoms in those receiving differing pharmacotherapies, and between those with and without psychiatric illnesses. The primary outcome was carbon monoxide confirmed abstinence from weeks 5-52 following a target quit date. Secondary outcomes included neuropsychiatric (i.e., depression, suicidal ideation, anxiety, anger) and withdrawal symptoms. Smokers (N=737) were randomly assigned to one of three treatment conditions, and were scheduled to attend 8 follow-up appointments over 12 months. All participants received 6-15 minute practical counseling sessions with nurse counselors experienced in treating tobacco dependence. We expect that the results will lead to an enhanced understanding of the efficacy of these pharmacotherapies, including those with a history of psychiatric illness.