Naltrexone plus bupropion reduces cigarette smoking in individuals with methamphetamine use disorder: A secondary analysis from the CTN ADAPT-2 trial

Abstract

Introduction: Methamphetamine (MA) use is marked by high rates of comorbid tobacco smoking, which is associated with more severe drug use and worse clinical outcomes compared to single use of either drug. Research has shown the combination of naltrexone plus oral bupropion (NTX-BUP) improves smoking cessation outcomes in non-MA-using populations. In the Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) study, NTX-BUP successfully reduced MA use. Our aim in this secondary data analysis was to examine changes in cigarette smoking among the subgroup of participants reporting comorbid tobacco use in the ADAPT-2 trial.

Methods: The multi-site ADAPT-2 study used a randomized, double blind, sequential parallel comparison design to evaluate treatment with extended-release injectable NTX (380 mg every 3 weeks) combined with once-daily oral extended-release BUP (450 mg/day) vs matching injectable and oral placebo in outpatients with moderate or severe MA use disorder. The study assessed smoking outcomes, based on self-reported timeline followback (TLFB) data, twice/week for 13 weeks.

Results: Of the 403 participants in the ADAPT-2 trial, 290 reported being current cigarette smokers (71.9 %). The study found significant differences (p's < 0.0001) for each smoking outcome indicating greater change in the proportion of nonsmoking days, number of cigarettes smoked per week, and consecutive nonsmoking days, all favoring the group receiving NTX-BUP versus placebo.

Conclusions: NTX-BUP was associated with significant reductions in self-reported cigarette smoking in the context of concurrent treatment for MA use disorder. These off-target medication effects warrant prospective investigation using biochemically confirmed measures of smoking abstinence. The development of NTX-BUP as a co-addiction treatment strategy has a potential for high public health impact.

Keywords: ADAPT-2 trial; Bupropion; Co-occurring substances; Combination pharmacotherapy; Methamphetamine; Naltrexone; Tobacco use.

Fig. 1.

Panel A shows the proportion of non-smoking days per week by medication group by Stage 1 (weeks 1 through 6) and Stage 2 (weeks 7 through 12). NTX-BUP refers to the combination of naltrexone and bupropion. In Stage 2, placebo/NTX-BUP refers to participants in the placebo group who did not have a response in Stage 1, defined as at least three methamphetamine-negative urine samples, and were assigned to the NTX-BUP group in Stage 2. Placebo/placebo refers to participants in the placebo group who did not have a response in Stage 1 and were assigned to placebo in Stage 2. Panel B shows cigarettes smoked per week by medication group across stages of the trial. For both smoking outcomes, the effect of medication group was significant in each stage and overall, p < 0.05.

Fig. 2.

Consecutive non-smoking days by medication group for Stage 1 (weeks 1 through 6) and Stage 2 (weeks 7 through 12).