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Naltrexone-Bupropion Helps for Meth Addiction, but Not a Lot

— More people on treatment had negative urine samples after 6 weeks

Ƶ MedicalToday
A small zip lock bag of methamphetamine crystals

A combination of naltrexone and bupropion was helpful in slightly reducing drug use for those struggling with methamphetamine use disorder, according to a double-blind, placebo-controlled study.

During the 12-week trial, 13.6% of participants treated with 380-mg extended-release injectable naltrexone (Vivitrol) every 3 weeks plus 450 mg/day of oral extended-release bupropion (Wellbutrin) had at least three methamphetamine-negative urine samples versus only 2.5% of those who were on placebo (11.1% weighted difference, P<0.001), reported Madhukar Trivedi, MD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues.

Those on combination naltrexone and bupropion also had a nearly 10% lower weekly methamphetamine craving score on the visual analog scale, the group wrote in the .

Additionally, the treatment group had a modest 1% lower depression score on the Patient Health Questionnaire 9 scale and a 4% higher score on the Treatment Effectiveness Assessment, which specifically measures reduced substance use and improvements in lifestyle, health, and community and interpersonal interactions.

"The participants in our trial were severely affected by methamphetamine use disorder, with almost daily use before entry into the trial," the researchers noted, adding that there is currently no FDA-approved medication indicated for the treatment of this disorder.

Naltrexone, an opioid-receptor antagonist, has already been established as an effective treatment for opioid use disorder. The atypical antidepressant bupropion, a norepinephrine-dopamine reuptake inhibitor, is currently indicated for major depression and smoking cessation and is thought to reduce feelings of dysphoria associated with methamphetamine withdrawal.

In the first stage of the trial, a total of 403 individuals with moderate or severe methamphetamine use disorder were randomly assigned in a 0.26:0.74 ratio to receive combination naltrexone and bupropion or a placebo injectable-oral combination for 6 weeks. The majority of the study participants were white men.

In this stage, 16.5% (18 of 109) of participants in the active treatment group had a treatment response, defined as at least three methamphetamine-negative urine samples out of four samples at the end of 6 weeks. In contrast, only 3.4% (10 of 294) of those on placebo had achieved this same treatment response.

From there, the researchers re-randomized participants from the placebo group who didn't have this treatment response in a 1:1 ratio to receive naltrexone plus bupropion or placebo for another 6 weeks. In this second stage, which included 225 participants, 11.4% (13 of 114) of the participants in the treatment group achieved a response -- at least three methamphetamine-negative urine samples -- while only 1.8% (2 of 111) of those on placebo achieved this response.

During both trial stages, the participants came into the clinic twice a week to provide urine samples. Samples were vetted for validity based on temperature (between 90° to 100°F).

Overall, the rate of serious adverse events was low with the treatment, occurring in only 3.6% of those who received naltrexone-bupropion. The most common adverse events reported were gastrointestinal disorders (nausea, vomiting, and constipation), nervous system-related symptoms like tremor and headache, and psychiatric symptoms like anxiety and anorexia, as well as malaise and hyperhidrosis.

"Replication of our trial results in a more naturalistic effectiveness design could be a next step," Trivedi's group suggested.

A low inclusion of women and participant self-reporting of the oral bupropion half of the treatment regimen were acknowledged as study limitations.

  • author['full_name']

    Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures

The study was supported by awards from the National Institute on Drug Abuse (NIDA) of the National Institutes of Health and by the Department of Health and Human Services. Alkermes provided Vivitrol and matched placebo free of charge under a written agreement with NIDA.

Trivedi reported relationships with AcademyHealth, Acadia, Alkermes, Allergan, Alto Neuroscience, Axsome Therapeutics, Boehringer Ingelheim, Vital Signs GreenLight, Janssen, Jazz Pharmaceuticals, Lundbeck, Medscape, Merck Sharp and Dohme, MSI Methylation Sciences, Myriad Neuroscience, Navitor, Otsuka, Oxford PharmaGenesis, Perception Neuroscience Holdings, Pharmerit International, Sage Therapeutics, Signant Health, Takeda Pharmaceuticals America, Applied Clinical Intelligence, Engage Health Media, Janssen Research & Development, Johnson & Johnson Health Care Systems, and the Patient-Centered Outcomes Research Institute. Other authors also reported disclosures.

Primary Source

New England Journal of Medicine

Trivedi MH, et al "Bupropion and naltrexone in methamphetamine use disorder" N Engl J Med 2021; DOI: 10.1056/NEJMoa2020214.