Bupropion and Naltrexone in Methamphetamine Use Disorder.
Abstract
<h4>Background</h4>The use of naltrexone plus bupropion to treat methamphetamine use
disorder has not been well studied.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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. (Funded by the National Institute
on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).
Type
Journal articleSubject
HumansAmphetamine-Related Disorders
Methamphetamine
Bupropion
Naltrexone
Narcotic Antagonists
Delayed-Action Preparations
Drug Therapy, Combination
Administration, Oral
Injections
Double-Blind Method
Adolescent
Adult
Aged
Middle Aged
Female
Male
Medication Adherence
Young Adult
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https://hdl.handle.net/10161/24797Published Version (Please cite this version)
10.1056/nejmoa2020214Publication Info
Trivedi, Madhukar H; Walker, Robrina; Ling, Walter; Dela Cruz, Adriane; Sharma, Gaurav;
Carmody, Thomas; ... Shoptaw, Steven (2021). Bupropion and Naltrexone in Methamphetamine Use Disorder. The New England journal of medicine, 384(2). pp. 140-153. 10.1056/nejmoa2020214. Retrieved from https://hdl.handle.net/10161/24797.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Augustus John Rush
Adjunct Professor in the Department of Psychiatry and Behavioral Sciences

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