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Combination of Bupropion and Naltrexone for Treatment of Methamphetamine Use Disorder Shows Promise

January 3, 2021
Meg Brunner, MLIS
Citation: Trivedi MH, et al. Bupropion and naltrexone in methamphetamine use disorder. New England Journal of Medicine 2021;384:140-153
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Methamphetamine use and its associated harms have been increasing, and effective treatment is lacking. Small studies have found bupropion or naltrexone (separately) to have some efficacy, so researchers decided to try to combine them to see if that might boost their effects.

This multi-site, double-blind, placebo-controlled trial, CTN-0068 (Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder), was designed to evaluate the efficacy and safety of extended-release injectable naltrexone (380mg every 3 weeks) plus oral extended-release bupropion (450mg per day) in adults with moderate or severe methamphetamine use disorder (MUD).

DoctorsIn the first stage of the trial, participants were randomly assigned to receive either the two medications or two placebos for 6 weeks. Those in the placebo group who didn’t have a response in stage 1 underwent randomization again and were newly assigned to receive either naltrexone-bupropion or placebos for an additional 6 weeks.

The primary outcome measured was at least 3 methamphetamine-negative urine samples out of 4 obtained at the end of stage 1 or stage 2.

A total of 403 participants were enrolled in stage 1, with 255 in stage 2. Overall, participants responded at a significantly higher rate in the naltrexone-bupropion group. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response.

Participants in the naltrexone-bupropion group also reported fewer cravings and greater improvements in their lives (as measured by a questionnaire).  

Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, sweating, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion in the trial.

Researchers determined the “number needed to treat” (NNT) was 9; in other words, 9 people would need to receive the treatment for 1 person to benefit from it. This NNT is comparable to most medical treatments for mental health disorders, including antidepressants prescribed for depression or naltrexone prescribed for alcohol use disorder.

Conclusions: Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low, but it was significantly higher than the response among those in the placebo group. Future research should build on this work by testing if longer naltrexone/bupropion treatment or concurrent behavioral therapy like contingency management could improve responses further.


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