A placebo-controlled trial of modafinil for nicotine dependence

Robert A. Schnoll, E. Paul Wileyto, Angela Pinto, Frank Leone, Peter Gariti, Steven Siegel, Kenneth A. Perkins, Charles Dackis, Daniel F. Heitjan, Wade Berrettini, Caryn Lerman

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)86-93
Number of pages8
JournalDrug and Alcohol Dependence
Issue number1-2
StatePublished - Nov 1 2008


  • Addiction
  • Modafinil
  • Nicotine dependence
  • Smoking cessation

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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