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 or severe methamphetamine use disorder 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 English medical journal, was conducted at various locations within the National Drug Abuse Institute’s Clinical Trials Network (NIDA CTN). NIDA is part of the National Institutes of Health.
“The resulting 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 approved drugs for the treatment of methamphetamine disorder, ”said NIDA director Nora D. Volkow, MD“ This advance demonstrates that medical treatment for methamphetamine disorder can help improve patient outcomes ”.
The study known as the Accelerated Development Study of Additive Drug Therapy for Methamphetamine Use Disorder, or ADAPT-2, was conducted from 2017 to 2019 at clinics in various community treatment programs across the country and involved 403 adult volunteers aged between 18 and 65 years with moderate to severe methamphetamine use disorder. All participants wished to reduce or discontinue the use of the drug and were randomly assigned to the treatment or control group.
In each of the six six-week phases, treatment group volunteers received an injection of prolonged-release naltrexone, a drug used to treat disorders of opioid and alcohol use, every three weeks and took daily prolonged-release tablets of bupropion, an antidepressant also used as a treatment to help nicotine cessation. Those in the control group received combined injectable and oral placebos over the same time periods. The investigators performed four urine tests for drugs 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 tests 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 who received the naltrexone / bupropion combination responded, compared with only 3.4% of those in the control group. Likewise, 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 of describing the usefulness of a medical intervention that indicates the number of people who would need to receive treatment to benefit a person. The researchers 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 disorders, including antidepressants prescribed for depression or naltrexone prescribed for alcohol use disorder .
Treatment group participants were assessed to have fewer cravings than those in the placebo group and reported greater improvements in their lives, as measured by a questionnaire called Treatment Effectiveness Assessment. It is important to note that there were no significant adverse effects associated with dual drug treatment. Treatment adherence was encouraged by adherence counseling and mobile app reminders and remained high at 77.4% and 82.0% in the treatment and placebo groups, respectively, in the final six weeks of the study.
“Long-term use of methamphetamine has been shown to cause diffuse changes in the brain, which can contribute to serious health consequences beyond addiction itself,” said Madhukar H. Trivedi, MD, of the Southwestern Medical Center at the University of Texas , in Dallas, who led the trial. “The good news is that some of the brain’s structural and neurochemical changes are reversed in people who recover, stressing 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 the risk of fatal overdose. Methamphetamine is a potent stimulant and, like other addictive drugs, hijacks reward pathways in the brain by raising levels of dopamine, a chemical in the brain associated with the repetition of actions that cause pleasurable sensations.
Finding treatments that interrupt these processes has been a challenge for scientists. Research suggests that bupropion may relieve the dysphoria associated with withdrawing methamphetamine, acting on the dopamine and norepinephrine systems. Relieving dysphoria can, in turn, reduce cravings and help prevent a return to meth use. Naltrexone can reduce the euphoric effects and cravings associated with using methamphetamine. In previous clinical studies, however, both bupropion and naltrexone administered alone have shown limited and inconsistent efficacy in treating the methamphetamine disorder. Now, in combination, these compounds appear to have an additive or synergistic effect.
Although 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 this methamphetamine disorder. The effectiveness of this combination of drugs is progress towards improving the treatment of this addiction.
The researchers recommend that future research be based on this work, testing whether longer treatment with naltrexone / bupropion or concomitant behavioral therapy, such as contingency management, brings even better responses. Contingency management, which uses motivational incentives and tangible rewards to help a person achieve his or her treatment goals, has proven to be the most effective therapy for stimulant use disorders, but is not widely used, due in part to a policy that limits the monetary value of the incentives allowed as part of the treatment.
About the National Drug Abuse Institute (NIDA): NIDA is a component of the National Institutes of Health, US Department of Health and Human Services. NIDA supports most research worldwide on the health aspects of drug use and dependence. The Institute runs a wide variety of programs to inform policy, improve practice and promote addiction science. For more information about NIDA and its programs, visit www.drugabuse.gov.
About the National Institutes of Health (NIH):
NIH, the country’s medical research agency, includes 27 institutes and centers and is a component of the United States Department of Health and Human Services. NIH is the leading federal agency that conducts and supports basic, clinical and translational medical research, and is investigating 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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