Date Added:

January 16, 2021

Journal/Publication:

The New England Journal of Medicine

Publisher:

The New England Journal of Medicine

Publication Date:

January 14, 2021

Issue:

2

Volume:

384

Pages:

140-153

URL:

Bupropion and Naltrexone in Methamphetamine Use Disorder

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa2020214

Keywords

MeSH

The combination of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) was more effective than placebo for helping adults abstain from methamphetamine. James W. Mold, MD, MPH

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BACKGROUND

The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied.

METHODS

We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone–bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone–bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses.

RESULTS

A total of 403 participants were enrolled in stage 1, and 225 in stage 2. 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. The weighted average response across the two stages was 13.6% with naltrexone–bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone–bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone–bupropion during the trial.

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 was higher than that among participants who received placebo

Author/s:

Madhukar H., Walker, Robrina, Ling, Walter, Cruz, Adriane, Sharma, Guarav, Carmody, Thomas, Ghitza, Udi, Wahle, Aimee, Kim, Mora, Shores-Wilson, Kathy, Sparenborg, Steven, Coffin, Phillip