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.
Schnoll
Robert A
RA
Department of Psychiatry, Abramson Cancer Center, and Annenberg Public Policy Center, University of Pennsylvania, Philadelphia, PA, United States. schnoll@mail.med.upenn.edu
Wileyto
E Paul
EP
Pinto
Angela
A
Leone
Frank
F
Gariti
Peter
P
Siegel
Steven
S
Perkins
Kenneth A
KA
Dackis
Charles
C
Heitjan
Daniel F
DF
Berrettini
Wade
W
Lerman
Caryn
C
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