A controlled trial of naltrexone augmentation of nicotine replacement therapy for smoking cessation.
BACKGROUND
Many smokers remain refractory to current therapies, which only partially address weight gain after smoking cessation. Thus, this study evaluated whether naltrexone hydrochloride augmentation of nicotine patch therapy improves smoking abstinence and reduces postcessation weight gain more than nicotine patch therapy alone and at what dose.


METHODS
Six-week double-blind placebo-controlled trial with follow-up in an outpatient research center. Four hundred individuals who smoked 20 or more cigarettes daily were randomly assigned to treatment for 6 weeks with a 21-mg nicotine patch and oral naltrexone hydrochloride (0, 25, 50, or 100 mg/d) after equal random treatment assignment and followed up for 1 year after randomization. The a priori specified primary end points were prolonged 4-week cigarette abstinence after a 2-week grace period in the intent-to-treat sample and weight gain in these abstainers.


RESULTS
We found no significant differences in prolonged 4-week abstinence (P = .49) or 6-week continuous abstinence after the quit date (P = .12) during treatment in the intent-to-treat analysis. Among 295 treatment completers, the 100-mg dose was associated with higher continuous abstinence rates (71.6%) compared with placebo (48%) (odds ratio, 2.73; 95% confidence interval, 1.39-5.39; P<.01). Among continuous abstainers, the 25-mg naltrexone hydrochloride group gained significantly less weight (mean +/- SEM, 0.7 +/- 0.31 kg) than the placebo group (mean +/- SEM, 1.9 +/- 0.33 kg; P<.01). Similar naltrexone dose effects on weight were found for those with prolonged abstinence and treatment completers, irrespective of abstinence.


CONCLUSIONS
The 100-mg dose of naltrexone hydrochloride appears the most promising for augmenting the efficacy of the nicotine patch on smoking cessation outcomes but requires further study. The significant weight reduction with low-dose naltrexone therapy suggests that it may be useful as a second-line treatment for weight-concerned smokers.
Department of Psychiatry, Yale University School of Medicine, Connecticut Mental Health Center, New Haven 06519, USA. stephanie.omalley@yale.edu
Stephanie S
SS
O'Malley
Judith L
JL
Cooney
Suchitra
S
Krishnan-Sarin
Joel A
JA
Dubin
Sherry A
SA
McKee
Ned L
NL
Cooney
Amy
A
Blakeslee
Boris
B
Meandzija
Denise
D
Romano-Dahlgard
Ran
R
Wu
Robert
R
Makuch
Peter
P
Jatlow
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000553:Ambulatory Care; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D009538:Nicotine / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D016540:Smoking Cessation / Q000379:methods*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D015430:Weight Gain
D009292:Narcotic Antagonists; D018722:Nicotinic Agonists; D009271:Naltrexone; D009538:Nicotine