News release
Wednesday, January 13, 2021
A combination of two drugs, injectable naltrexone and oral bupropion, was safe and effective in the treatment of adults with moderate or severe methamphetamine use disorder in a double-blind, placebo-controlled phase III clinical trial. The findings 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 is difficult to treat and overcome. The research, published today in The New England Journal of Medicine, was conducted at multiple locations within the National Institute on Drug Abuse Clinical Trials Network (NIDA CTN). NIDA is part of the National Institutes of Health.
“The opioid crisis and resulting 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 approved drugs for the treatment of a methamphetamine use, “said NIDA Director Nora D. Volkow, MD.” This advance shows that medical treatment for a methamphetamine use disorder can help improve outcomes for the patient. “
The study known as the Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder, or ADAPT-2, was conducted from 2017 to 2019 in clinics across multiple treatment programs nationwide and enrolled 403 adult volunteers aged 18 to 65 with moderate to severe methamphetamine use disorder. All participants wanted 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 phases, volunteers in the treatment group received an injection of prolonged-release naltrexone, a drug used to treat disorders in opioids and alcohol use, every three weeks, and took bupropion extended-release tablets daily. , an antidepressant, in. also used as a treatment to promote nicotine withdrawal. Those in the control group received matched injectable and oral placebos over the same time periods. Researchers performed four urine drugs at the end of each phase of the study. Participants were considered to have responded to treatment if at least three of the four urine screens were negative.
Overall, the participants responded significantly higher in the treatment group. At week five and six screening, 16.5% of those who received the naltrexone / bupropion combination responded, compared to only 3.4% of those in the control group. Similarly, 11.4% of the treatment group responded at screening at weeks 11 and 12, compared to 1.8% of the control group. Researchers calculated that the number required to treat (NNT) was 9. NNT is a way of describing the usefulness of a medical intervention that indicates how many people would need treatment for one person to benefit. The researchers reported that, with an NNT of 9, the benefit of naltrexone / bupropion as a treatment for the methamphetamine use disorder is comparable to most medical treatments for mental disorders, including antidepressants prescribed for depression or naltrexone prescribed for alcohol use disorders.
Participants in the treatment group were assessed for less cravings than those in the placebo group and reported greater improvements in their lives as measured by a questionnaire called the Treatment Effectiveness Assessment. Importantly, no significant side effects were associated with the dual drug treatment. Adherence was encouraged by adherence and reminders via mobile apps and remained high at 77.4% and 82.0% in the treatment and placebo groups, respectively, in the last six weeks of the study.
“Long-term abuse of methamphetamine causes diffuse changes in the brain that can contribute to serious health consequences beyond the addiction itself,” says Madhukar H. Trivedi, MD, of the Southwestern Medical Center at the University of Texas, Dallas. , who led the trial. “The good news is that some of the structural and neurochemical brain changes are reversed in people who recover, underscoring the importance of identifying new and more effective treatment strategies.”
Methamphetamine use disorder is a serious illness often associated with serious medical and mental health complications and a risk of fatal overdose. Methamphetamine is a powerful stimulant and, like other addictive drugs, it hijacks reward pathways in the brain by increasing levels of dopamine, a brain chemical associated with repetitive actions that cause pleasurable feelings.
Finding treatments that disrupt these processes has been a challenge for scientists. Research suggests that bupropion may relieve dysphoria associated with methamphetamine withdrawal by acting on the dopamine and norepinephrine systems. In turn, alleviating dysphoria can reduce cravings and help prevent the return to methamphetamine use. Naltrexone can reduce the euphoric effects and the craving for methamphetamine. However, in previous clinical studies, both bupropion and naltrexone, administered alone, showed limited, inconsistent efficacy in the treatment of methamphetamine use disorder. Now these compounds appear to have an additive or synergistic effect in combination.
While there are drugs approved by the U.S. Food and Drug Administration for other substance use disorders, no drugs have yet received FDA approval for the methamphetamine use disorder. The effectiveness of this drug combination is advancement in improving the treatment of this addiction.
The researchers recommend that future research builds on this work by testing whether longer treatment with naltrexone / bupropion or concomitant behavioral therapy, such as contingency management, yields even better responses. 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 stimulant use disorders, but is not widely adopted, in part as a result of policies that limits the monetary value of permitted incentives as part of the treatment.
About the National Institute on Drug Abuse (NIDA): NIDA is part of the National Institutes of Health, the United States Department of Health and Human Services. NIDA supports most of the global research on the health aspects of drug use and addiction. The institute runs a wide variety of programs to inform policy, improve practice, and advance addiction science. To learn more 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 part of the United States Department of Health and Human Services. NIH is the premier federal agency that conducts and supports basic, clinical and translational medical research, investigating the causes, treatments, and cures for both common and rare diseases. To learn more about NIH and its programs, visit www.nih.gov.
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