A placebo-controlled trial of modafinil for nicotine dependence

Background: Nicotine deprivation symptoms, including fatigue and attentional deficits, predict relapse following smoking cessation. Modafinil (Provigil), a wakefulness medication shown to have efficacy for the treatment of cocaine addiction, was tested as a novel therapy for nicotine dependence in a double-blind placebo-controlled trial. Methods: One hundred and fifty-seven treatment-seeking smokers received brief smoking cessation counseling and were randomized to: (1) 8 weeks of modafinil (200 mg/day), or (2) 8 weeks of placebo. The primary outcome was biochemically verified 7-day point prevalence abstinence at the end of treatment (EOT). Secondary outcomes included cigarette smoking rate and post-quit nicotine deprivation symptoms (e.g., negative affect, withdrawal). Results: In this interim study analysis, EOT quit rates did not differ between treatment arms (42% for placebo vs. 34% for modafinil; OR = 0.67 [0.34-1.31], p = 0.24). Further, from the target quit date to EOT, the daily smoking rate was 44% higher among non-abstainers in the modafinil arm, compared to non-abstainers in the placebo arm (IRR = 1.44, CI₉₅ = 1.09-1.89, p < 0.01). Modafinil-treated participants also reported greater increases in negative affect and withdrawal symptoms, vs. participants randomized to placebo (ps < 0.05). Conclusions: These data do not support the use of modafinil for the treatment of nicotine dependence and, as a consequence, this trial was discontinued. Cigarette smoking should be considered when modafinil is prescribed, particularly among those with psychiatric conditions that have high comorbidity with nicotine dependence.