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 disorder in a phase III, double-blind, placebo-controlled clinical trial. The results suggest that this combination therapy may be a promising addition to current approaches to treatment, 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 conducted at various sites in the National Drug Abuse Institute (NIDA CTN) clinical trial network. NIDA is part of the National Institutes of Health.
“The resulting opioid crisis and overdose deaths in the United States are already well known, but what is least recognized is that there is a growing crisis of overdose deaths that include methamphetamine and other stimulants. However, unlike of opioids, there are currently no drugs approved to treat methamphetamine use disorder, “said NIDA director Nora D. Volkow, MD.” This breakthrough shows that medical treatment for methamphetamine use disorder it can help improve patient outcomes. “
The study known as the Accelerated Developmental Study of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder, or ADAPT-2, was conducted from 2017 to 2019 in clinics of multiple community treatment programs throughout the country and enrolled 403 adult volunteers aged 18 to 65 years with moderate to severe methamphetamine use disorder. All participants wished to reduce or stop using the drug and were randomly assigned to the treatment or control group.
At each of the two six-week stages, treatment group volunteers were given an injection of prolonged-release naltrexone, a drug used to treat alcohol and opioid use disorders, every three weeks, and took daily prolonged-release tablets of bupropion, an antidepressant is also used as a treatment to help quit nicotine. Those in the control group received coincident injectable and oral placebo during the same time periods. The investigators performed four urine drug tests at the end of each stage of the trial. Participants were considered to have responded to treatment if at least three of the four urine screens were negative.
Overall, participants responded to a significantly higher rate in the treatment group. When examined at five and six weeks, 16.5% of those receiving 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 be treated (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 researchers reported that, with an 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 to have fewer desires than those in the placebo group and reported better improvements in their lives, as measured by a questionnaire called Evaluation of Treatment Effectiveness. Importantly, there were no significant adverse effects associated with dual-medication treatment. Adherence to treatment was encouraged through adherence counseling and mobile app reminders 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 methamphetamine abuse has been shown to cause diffuse changes in the brain, which can contribute to serious health consequences beyond addiction,” said Madhukar H. Trivedi, MD, of Southwestern Medical Center of the University of Texas, Dallas, which led the trial. “The good news is that some of the structural and neurochemical brain changes 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 serious medical and mental health complications and a risk of fatal overdose. Methamphetamine is a powerful stimulant and, like other addictive drugs, hijacks the reward pathways in the brain by increasing levels of dopamine, a brain chemical associated with repeated 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. Relieving dysphoria in turn can reduce cravings and help prevent a return to methamphetamine use. Naltrexone may reduce the euphoric effects and cravings associated with methamphetamine intake. However, in previous clinical studies, both bupropion and naltrexone administered showed only limited and inconsistent efficacy in the treatment of methamphetamine use disorder. Now, in combination, these compounds appear to have an additive or synergistic effect.
While there are U.S.-approved drugs for other substance use-related disorders, there are still no drugs that have received FDA approval for the methamphetamine disorder. The effectiveness of this combination of drugs is the progress towards improving the treatment of this addiction.
Researchers recommend that future research be based on this work to see if longer treatment with naltrexone / bupropion or concurrent behavioral therapy, such as contingency management, provides even better answers. Contingency 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 used, resulting in part of a policy that limits the monetary value of admitted incentives. as part of the treatment.
Regarding the National Institute on Drug Abuse (NIDA): NIDA is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the global research on the health aspects of drug use and addiction. The Institute conducts a wide variety of programs to inform policies, improve practice, and advance addiction sciences. For more information about NIDA and its programs, visit www.drugabuse.gov.
Regarding the National Institutes of Health (NIH):
NIH, the country’s medical research agency, includes 27 institutes and centers and is a component of the U.S. 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 for common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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