Varenicline efficacy and safety among methadone maintained smokers: A randomized placebo-controlled trial

Aims: To test the efficacy and safety of varenicline as an aid to smoking cessation in methadone-maintained smokers. Design: Multicenter, randomized, double-blind, placebo-controlled trial with random assignment to 12 weeks of varenicline 1mg twice daily (n=57) or matched placebo (n=55), with in-person and telephone counseling. Setting: Urban methadone programs in the Bronx, New York City, New York, USA. Participants: Methadone maintenance patients, smoking ≥5 cigarettes/day, interested in quitting, stable in methadone treatment, without current Axis I psychiatric disorders, suicidal ideation or recent suicide attempts. Measurements: Seven-day point prevalence abstinence verified by expired carbon monoxide (CO)<8 parts per million at week 12 (primary outcome); carbon monoxide (CO)-verified abstinence, cigarettes/day, incident Axis I psychiatric illness, suicidal ideation or serious adverse events (SAEs) at weeks 2, 4, 8, 12 or 24 (secondary outcomes). Findings: Baseline demographic, smoking and clinical factors were similar between groups. Retention at 24 weeks was 90%. Subjects receiving varenicline were more likely than those receiving placebo to achieve abstinence (10.5 versus 0%, P=0.03; effect size 10.5%, 95% confidence interval (CI)=4.4-19.3%) and to reduce smoking (median five versus two cigarettes/day, P<0.001) at 12 weeks. These effects were not maintained after drug treatment ceased. Incident psychiatric illness (OR=0.84, 95% CI=0.16, 4.4) and suicidality [odds ratio (OR)=0.88, 95% CI 0.2, 3.9] were not different between groups. There were no psychiatric or cardiac SAEs. Conclusions: Varenicline can aid short-term smoking abstinence in methadone-maintained smokers.