Naltrexone-bupropion more effective than placebo for methamphetamine use disorder

Responses to naltrexone-bupropion therapy combination among adults with methamphetamine use disorder were “low” but higher than responses to placebo, researchers said.

Currently, there are no FDA-approved treatments for methamphetamine use disorder, according to Madhukar H. Trivedi, MD, a professor in the department of psychiatry at the University of Texas Southwestern Medical Center, and colleagues.

“Long-term methamphetamine abuse has been shown to cause diffuse changes to the brain, which can contribute to serious health effects beyond addiction itself,” Trivedi said in a press release. “The good news is that some of the structural and neurochemical brain changes are reversed in people who recover, reaffirming the importance of new and more effective treatment strategies. to celebrate. ”

Trivedi and colleagues evaluated the efficacy of naltrexone-bupropion during a multisite, double-blind, two-stage, placebocontrolled trial. In the first phase of the trial, which was the first 6 weeks, Trivedi and colleagues randomized 403 patients with moderate or severe methamphetamine use disorder to receive 380 mg of extended-release injectable naltrexone every 3 weeks and 450 mg oral extended-dose bupropion daily (n = 109) or placebo equivalent (n = 294). In phase 2, also lasting 6 weeks, stage 1 patients who did not respond to placebo were randomly assigned to receive the same naltrexone-bupropion therapy (n = 114) or placebo (n = 111).

A 3-week Naltrexone administration schedule was chosen to “lower the blood levels of naltrexone that would be more likely to occur with a 4-week injection schedule,” the researchers wrote. New England Journal of Medicine. Starting on a randomized day or rerandomization, the researchers increased the extended-dose bupropion dose over 3 days to reach the maximum daily dose of 450 mg.

“If appropriate, doses could be reduced before week 13 to 300 mg daily to reduce side effects; clinicians were encouraged to try to take the dose back to the target dose, ”wrote the researchers.

Attacks were provided by probation staff. Patients were asked to use an app to monitor their adherence to oral medication and visited their test site to provide a urine sample twice a week.

According to Trivedi and colleagues, at the end of phase 1, 16.5% of patients in the naltrexone-bupropion group and 3.4% in the placebo group met the main endpoint: at least three urine samples out of four who may be negative for methamphetamine. At the end of level 2, these percentages were at 11.4% and 1.8%, respectively. The mean response with weight over all levels was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (P. <.001). The most common adverse events occurring more frequently across all levels in naltrexone-bupropion recipients vs placebo recipients were nausea (n = 73), vomiting (n = 25), headache (n = 24). , lactation (n = 18) and fat (n = 15). The P. value for all adverse events that occurred more frequently among the naltrexone-bupropion group than the control group was lower than 0.05.

“There is a growing crisis of hypertensive deaths involving methamphetamine and other stimulants,” Nora D. Volkow, MD, director of the National Institute for Drug Misuse, he said in the news. “This advancement demonstrates that medical treatment for methamphetamine use disorders can help improve patient outcomes.”

The researchers suggested that future trials examine how patients with methamphetamine use disorder respond to longer doses of naltrexone-bupropion treatment or concomitant behavioral therapy, depending on their release.