A placebo-controlled trial of modafinil-nicotina

Drug Alcohol Depend. 2008 Nov 198(1-2):86-93. Epub 2008 Jun 9. Links

A placebo-controlled trial of modafinil for nicotine dependence.

Schnoll RA, Wileyto EP, Pinto A, Leone F, Gariti P, Siegel S, Perkins KA, Dackis C, Heitjan DF, Berrettini W, Lerman C.
Department of Psychiatry, Abramson Cancer Center, and Annenberg Public Policy Center, University of Pennsylvania, Philadelphia, PA, United States. schnoll@mail.med.upenn.edu

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 (200mg/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.