Press release
Wednesday, January 13, 2021
A combination of two drugs, injectable naltrexone and oral bupropion, was safe and effective in treating adults with moderate to severe methamphetamine use in a double-blind, placebo-controlled phase III clinical trial. The results suggest that this combination therapy may be a promising addition to current treatment approaches, such as cognitive behavioral therapy and contingency management interventions, for a very serious condition that remains difficult to treat and overcome. The research, published today in The New England Journal of Medicine, was performed in several locations within the network of the National Institute for Clinical Drug Abuse Testing (NIDA CTN). NIDA is part of the National Institutes of Health.
“The opioid crisis and overdose deaths in the United States are now well known, but what is less recognized is that there is a growing crisis of overdose deaths involving methamphetamine and other stimulants. However, unlike opioids, there are currently no drugs approved to treat methamphetamine use disorder, “said NIDA Director Nora D. Volkow, MD. This advance demonstrates that medical treatment for methamphetamine use can help improve patient outcomes. “
The study known as Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder, or ADAPT-2, was conducted in 2017-2019 in clinics from several community treatment programs nationwide and enrolled 403 volunteers. adults aged 18 to 65 years with moderate to severe methamphetamine use disorder. All participants wished to reduce or discontinue use of the drug and were randomly assigned to the treatment or control group.
In each of the two six-week stages, volunteers in the treatment group were given an injection of prolonged-release naltrexone, a medicine used to treat opioid and alcohol use disorders, every three weeks, and took daily tablets. prolonged bupropion, an antidepressant also used as a treatment to help stop nicotine. Those in the control group received assorted injectable and oral placebo over the same time periods. Investigators performed four screens of drugs in the urine at the end of each stage of the trial. Participants were considered to have responded to treatment if at least three of the four urines were negative.
Overall, participants responded to a significantly higher rate in the treatment group. When examined during weeks five and six, 16.5% of those given the naltrexone / bupropion combination responded, compared with only 3.4% of those in the control group. Similarly, when examined at weeks 11 and 12, 11.4% of the treatment group responded, compared with 1.8% of the control group. The researchers calculated that the number needed to treat (NNT) was 9. NNT is a way to describe the usefulness of a medical intervention that indicates the number of people who should receive treatment to benefit a person. The investigators reported that with a NNT of 9, the benefit of naltrexone / bupropion as a treatment for methamphetamine use disorder is similar to most medical treatments for mental health disorders, including antidepressants prescribed for depression or naltrexone prescribed for alcohol use disorder.
Participants in the treatment group were assessed as having less appetite than those in the placebo group and reported greater improvements in their lives, as measured by a questionnaire called Assessing Treatment Effectiveness. Importantly, there were no significant adverse effects associated with treatment with two drugs. Adherence to treatment was encouraged by counseling on adherence and reminders for mobile applications and remained high at 77.4% and 82.0% in treatment groups and placebo, respectively, in the last six weeks of study.
“Long-term methamphetamine abuse has been shown to cause diffuse changes in the brain that can contribute to serious health consequences beyond the addiction itself,” said Madhukar H. Trivedi, MD, of the University of Texas Southwestern Medical Center. , Dallas, who led the process. The good news is that some of the structural and neurochemical changes in the brain are reversed in people recovering, emphasizing the importance of identifying new and more effective treatment strategies.
Methamphetamine use disorder is a serious illness, often associated with severe medical and mental complications and a risk of fatal overdose. Methamphetamine is a powerful stimulant and, like other addictive drugs, diverts the reward pathways in the brain by increasing the level of dopamine, a brain chemical associated with repeated actions that cause pleasant feelings.
Finding treatments that disrupt these processes has been a challenge for scientists. Research suggests that bupropion may alleviate dysphoria associated with methamphetamine withdrawal by acting on the dopamine and norepinephrine systems. Relief dysphoria can, in turn, reduce cravings and prevent a return to methamphetamine use. Naltrexone may reduce the euphoric effects and cravings associated with methamphetamine use. However, in previous clinical trials, both bupropion and naltrexone alone showed limited, inconsistent efficacy in treating methamphetamine use disorder. Now, in combination, these compounds appear to have an additive or synergistic effect.
Although there are US-approved drugs for other substance use disorders, no drug has yet received FDA approval for methamphetamine use disorder. The effectiveness of this combination of drugs is the progress towards improving the treatment of this addiction.
Investigators recommend that future research build on this work by testing whether longer treatment with naltrexone / bupropion or concomitant behavioral therapy, such as contingency management, provides better answers. Emergency management, which uses motivational incentives and tangible rewards to help a person achieve their treatment goals, has proven to be the most effective therapy for stimulus use disorders, but is not widely used, resulting in -a policy that limits the monetary value of the allowed incentives. as part of treatment.
About the National Institute on Drug Abuse (NIDA): NIDA is a component of the National Institutes of Health, US Department of Health and Human Services. NIDA supports most research in the world on the health issues of drug use and dependence. The institute runs a wide variety of programs to inform policies, improve practice and advance the science of addiction. For more information about NIDA and its programs, visit www.drugabuse.gov.
About the National Institutes of Health (NIH):
NIH, the national medical research agency, includes 27 institutes and centers and is a component of the US Department of Health and Human Services. NIH is the leading federal agency that conducts and supports basic, clinical, and translational medical research and investigates the causes, treatments, and cures of both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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