Two-Drug Combo Promising for Methamphetamine Use Disorder

Extended-release injectable naltrexone combined with extended-release oral bupropion (NTX + BUPN) for moderate or severe methamphetamine use disorder was associated with a significant decrease in use of the drug, a new study showed.

Investigators leading the randomized clinical trial found a 27% increase in negative methamphetamine urine tests in the treatment group — indicating reduced use — compared with an 11% increase in negative urine tests in control participants.

“These findings have important implications for pharmacological treatment for methamphetamine use disorder. There is no FDA-approved medication for it, yet methamphetamine-involved overdoses have greatly increased over the past decade,” lead author Michael Li, MD, assistant professor-in-residence of family medicine at the David Geffen School of Medicine at UCLA, Los Angeles, said in a news release.

The study was published online on June 10 in Addiction.

Methamphetamine use has increased worldwide, from 33 million users in 2010 to 34 million in 2020, with overdose deaths rising fivefold in the United States over the past decade, the authors wrote.

A previous open-label study of NTX + BUPN showed efficacy for treating severe methamphetamine use disorder, and NTX and BUPN have each shown efficacy separately for this indication. 

This new study is the second phase of the multicenter ADAPT-2 trial, conducted between 2017 and 2019 in 403 participants with methamphetamine use disorder. In the first stage, 109 people received NTX + BUPN and 294 received placebo. 

The treatment group received extended-release NTX (380 mg) or placebo as an intramuscular injection on weeks 1, 4, 7 and 10. Extended-release BUPN or placebo tablets were administered weekly, with BUPN doses starting at 150 mg on day 1 and increasing to 450 mg by day 3. At week 13, participants received a tapering dose for 4 days before discontinuing.

As previously reported by Medscape Medical News, the two-drug combo was effective at reducing methamphetamine use at 6 weeks. The current analysis measured change in methamphetamine use during weeks 7-12 of the trial and in posttreatment weeks 13-16. 

Participants in the intervention group during stage 1 showed an additional 9.2% increase (P = .038) during stage 2 in their probability of testing negative for methamphetamine. This represented a total increase of 27.1% in negative urine tests across the complete 12 weeks of treatment, compared with a total 11.4% increase in negative tests in the placebo group. 

The 12-week increase in methamphetamine-negative urine tests in the intervention group was 15.8% greater (P = .006) than the increase in the placebo group.

There was no significant change in either group at posttreatment follow-up in weeks 13-16.

“Our findings suggest that ongoing NTX + BUPN treatment yields statistically significant reductions in methamphetamine-use that continue from weeks 7 to 12,” the authors wrote. The lack of change in methamphetamine use from weeks 13-16 corresponds to the conclusion of treatment in week 12, they added.

It “remains to be determined “whether continued use of NTX + BUPN treatment past 12 weeks would yield further reductions in use,” the authors wrote, noting that prior stimulant use disorder trials suggest that change in use is gradual and that sustained abstinence is unlikely in merely 12 weeks of a trial. Rather, it is dependent on treatment duration.

“This warrants future clinical trials to quantify changes in methamphetamine use beyond 12 weeks and to identify the optimal duration of treatment with this medication,” they concluded.

The study was funded by awards from the National Institute on Drug Abuse (NIDA), the US Department of Health and Human Services; the National Institute of Mental Health, and the O’Donnell Clinical Neuroscience Scholar Award from the University of Texas, Southwestern Medical Center. Alkermes provided Vivitrol (naltrexone for extended-release injectable suspension) and matched placebo free of charge for use in this trial under a written agreement with NIDA. Li reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper. 

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).