Naltrexone-bupropion treatment provides a higher response for methamphetamine use disorder

1. Combinatorial naltrexone and bupropion treatment were shown to have a higher response than placebo for patients with methamphetamine use disorder.

2. Furthermore, a higher adverse event frequency of nausea, dizziness, and tremor was seen with the combinatorial treatment.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Methamphetamine use disorder is highly prevalent throughout the United States, specifically in the Midwest and West where methamphetamine is a leading cause of overdose death. Currently, there is not a treatment for the disorder; however, naltrexone and bupropion, individually, have shown to be effective in the disorder treatment. Bupropion may reduce the dysphoria associated with methamphetamines, while naltrexone is effective in opioid use disorders. As such, this study assessed the efficacy of combinatorial treatment of naltrexone and bupropion for the treatment of methamphetamine use disorder. The study determined the combinatorial treatment had a high response than the placebo group. The randomized control trial was limited by the low representation of female participants in the study. Though the male-to-female ratio represents the incidence of amphetamine use disorder in the United States, the low female representation reduces the study’s results to be generalized. Nonetheless, this study’s results are significant, and its findings highlight a potential treatment for methamphetamine use disorder.

Click to read the study in NEJM

Relevant Reading: Randomized, placebo-controlled trial of bupropion in methamphetamine-dependent participants with less than daily methamphetamine use

In-Depth [randomized controlled trial]: This randomized control trial enrolled 403 participants in a multicenter study at eight sites in the United States. Participants included in the study were between 18 and 65 years of age, diagnosed with moderate to severe stimulant use disorder, and had two or more methamphetamine-positive urine samples within 10 days before randomization. Participants undergoing concurrent substance use disorder treatment were excluded from this study. The participants were randomized in a 0.26:0.74 ratio to receive naltrexone-bupropion or placebo therapy, respectively, during the first study stage. After which, participants in the placebo group without a response were randomized in a 1:1 ratio to receive naltrexone-bupropion or placebo therapy, respectively, for the second study stage. The primary endpoint was trial response defined as at least three methamphetamine-negative urine tests out of four at the end of each stage. In stage 1, regimen adherence was 75.1% in the treatment group compared to 83.5% in the placebo group. Furthermore, regimen adherence was 77.4% in the treatment group compared to 82.0% in the placebo group in stage 2. At the end of stage 1, the primary outcome was achieved in 16.5% (18 of 109 participants) of the treatment group and 3.4% (10 of 294 participants) of the placebo group. For stage 2, the primary outcome was achieved in 11.4% (13 of 114 participants) of the treatment group and 1.8% (2 of 111 participants) of the placebo group. Overall, the weighted response for the primary outcome was achieved for 13.6% in the treatment group and 2.5% in the placebo group. Taken together, a combinatorial naltrexone-bupropion treatment was shown to have a higher response than placebo for substance use disorder for methamphetamines.

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