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 (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.
Department of Psychiatry, Abramson Cancer Center, and Annenberg Public Policy Center, University of Pennsylvania, Philadelphia, PA, United States. schnoll@mail.med.upenn.edu
Robert A
RA
Schnoll
E Paul
EP
Wileyto
Angela
A
Pinto
Frank
F
Leone
Peter
P
Gariti
Steven
S
Siegel
Kenneth A
KA
Perkins
Charles
C
Dackis
Daniel F
DF
Heitjan
Wade
W
Berrettini
Caryn
C
Lerman
D000328:Adult; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009538:Nicotine / Q000009:adverse effects; D016540:Smoking Cessation; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis / Q000534:rehabilitation; D014029:Tobacco Use Disorder / Q000534:rehabilitation*
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D009538:Nicotine; D000077408:Modafinil