A new study has found that the combination of extended-release injectable naltrexone and extended-release oral bupropion (NTX + BUPN) resulted in a significant reduction in drug use in people with moderate to severe methamphetamine use disorder.
The researchers who led the randomized clinical trial found a 27% increase in negative methamphetamine urine tests in the treatment group – indicating lower use – while there was an 11% increase in negative urine tests in the control group.
“These findings have important implications for the pharmacologic treatment of methamphetamine use disorder. There is no FDA-approved drug for it, yet methamphetamine overdoses have increased dramatically over the past decade,” said the study’s lead author, Dr. Michael Li, assistant professor of family medicine at the David Geffen School of Medicine at UCLA in Los Angeles, in a press release.
The study was published online on June 10 in Seeks.
Methamphetamine use has increased worldwide, from 33 million users in 2010 to 34 million in 2020, with overdose deaths in the United States increasing fivefold over the past decade, the authors write.
A previous open-label study of NTX + BUPN demonstrated efficacy in the treatment of severe methamphetamine use disorder, and both NTX and BUPN demonstrated efficacy individually for this indication.
This new study is the second phase of the multicenter ADAPT-2 trial, which was conducted between 2017 and 2019 in 403 participants with methamphetamine use disorder. In the first phase, 109 people received NTX + BUPN and 294 received placebo.
The treatment group received extended-release NTX (380 mg) or placebo by intramuscular injection at weeks 1, 4, 7, and 10. Extended-release BUPN tablets or placebo 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 4-day tapering dose before discontinuing treatment.
As previously reported by Medical news from MedscapeThe two-drug combination was effective in reducing methamphetamine use after 6 weeks. The current analysis measured the change in methamphetamine use during weeks 7-12 of the study and weeks 13-16 after treatment.
An additional increase of 9.2% was recorded among participants in the intervention group during Phase 1 (P = .038) during Phase 2 in their probability of testing negative for methamphetamine. This represents an overall increase of 27.1% in negative urine tests over the entire 12-week treatment period, compared with an overall increase of 11.4% in negative tests in the placebo group.
The increase in methamphetamine-negative urine tests after 12 weeks was 15.8% higher in the intervention group (P = .006) than the increase in the placebo group.
At the post-treatment follow-up assessment from weeks 13 to 16, there was no significant change in either group.
“Our results suggest that continued NTX + BUPN treatment results in statistically significant reductions in methamphetamine use that are sustained from weeks 7 to 12,” the authors wrote. The lack of change in methamphetamine use from weeks 13 to 16 is consistent with treatment completion at week 12, they added.
It “remains to be seen whether continued treatment with NTX + BUPN beyond 12 weeks would result in further reductions in use,” the authors wrote, noting that previous studies of stimulant use disorder suggest that change in use is gradual and sustained abstinence is unlikely in just 12 weeks of a study. Rather, it depends on the duration of treatment.
“This warrants future clinical trials to quantify changes in methamphetamine use beyond 12 weeks and determine the optimal duration of treatment with this medication,” they concluded.
The study was funded by grants from the National Institute on Drug Abuse (NIDA), the U.S. Department of Health and Human Services, the National Institute of Mental Health, and the O’Donnell Clinical Neuroscience Scholar Award at the University of Texas, Southwestern Medical Center.. Alkermes provided Vivitrol (naltrexone extended-release suspension for injection) and matching placebo for use in this study at no charge under a written agreement with NIDA. Li reports no relevant financial relationships. Disclosures of the other authors are listed in the original paper.
Batya Swift Yasgur, MA, LSW, is a freelance writer with a consulting practice in Teaneck, New Jersey. She writes regularly for numerous medical publications, including Medscape and WebMD, and is the author of several consumer-focused 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).
