Bupropion and naltrexone for smoking cessation: A double-blind randomized placebo-controlled clinical trial

Abstract

Combination of non-nicotine pharmacotherapies has been underexamined for cigarette smoking cessation. A randomized, double-blind, parallel-group double-dummy study evaluated two medications, bupropion (BUP) and naltrexone (NTX), in treatment-seeking cigarette smokers (N = 121) over a 7-week treatment intervention with 6-month follow-up. Smokers were randomized to either BUP (300 mg/day) + placebo (PBO) or BUP (300 mg/day) + NTX (50 mg/day). The primary outcome was biochemically verified (saliva cotinine, carbon monoxide) 7-day, point-prevalence abstinence. BUP + NTX was associated with significantly higher point-prevalence abstinence rates after 7-weeks of treatment (BUP + NTX, 54.1%; BUP + PBO, 33.3%), P = 0.0210, but not at 6-month follow-up (BUP + NTX, 27.9%; BUP + PBO, 15.0%), P = 0.09. Continuous abstinence rates did not differ, P = 0.0740 (BUP + NTX, 26.2%; BUP + PBO, 13.3%). Those receiving BUP + NTX reported reduced nicotine withdrawal, P = 0.0364. The BUP + NTX combination was associated with elevated rates of some side effects, but with no significant difference in retention between the groups.

Trial registration: ClinicalTrials.gov NCT00419731.

Figure 1

Study design showing the three phases of the trial: baseline, treatment, and follow-up. The targeted quit date occurred during Week 1 of treatment, following a 7-day medication induction phase. At Weeks 5, 7 (end of treatment), 1-month follow-up, 3-month follow-up, and 6-month follow-up, saliva cotinine samples were collected from those reporting abstinence from tobacco in the preceding week and having a CO ≤ 8 P.P.M. Participants discontinued medication at the end of the treatment phase (Week 7). The initial counseling session prior to TQD lasted 20 minutes. All subsequent sessions included counseling lasting approximately 10 minutes.

Figure 2

Study participant flow diagram (CONSORT).

Figure 3

Participant retention figure. Proportion of subject retained in the study over treatment and follow-up periods.

Figure 4

Biochemically-confirmed (saliva cotinine), 7-day, point-prevalence abstinence rates significantly differed between medication groups with BUP+NTX subjects. Estimated (derived the logistic statistical model) and observed abstinence rates (presented in parentheses) are displayed at each time point.

Figure 5

Nicotine withdrawal symptoms as measured by the MWSC, varied significantly as a function of Medication, Time, and their interaction.