Combination of two drugs can help treat methamphetamine addiction for some, new clinical trial data shows 

As rates of methamphetamine overdose soar in the United States, one of the biggest challenges for both people who use stimulants and clinicians is that there are no approved treatments for this type of addiction — unlike the three medications authorized to treat opioid use disorders.

But in a new study, researchers found that a combination of two existing drugs — one, a treatment for opioid addiction, and the other, an antidepressant — can help some people who use methamphetamine regularly cut back. In a clinical trial, the researchers reported Wednesday, 13.6% of participants treated with the two drugs had repeated urine tests free of methamphetamine, compared to just 2.5% of those who were given placebos.

“This is a very serious illness with fatal consequences for which there are no available treatments,” said Madhukar Trivedi, the chief of the mood disorders division at the University of Texas Southwestern Medical Center and the lead author of the paper, which was published in the New England Journal of Medicine. “There is hope now for methamphetamine use disorder.”

Some experts not involved with the trial were similarly enthused.

“Methamphetamine use disorder is a really difficult disorder to treat, and a really devastating illness,” said Miriam Komaromy, the medical director of Boston Medical Center’s Grayken Center for Addiction. “This study provides one of the very few medication tools that we have reason to believe is helpful for treating methamphetamine use disorder, so I’m actually quite excited.”

The two drugs used in the trial were injectable naltrexone and oral bupropion. The former is a treatment for opioid use disorder — it’s more commonly known by the brand name Vivitrol — and is also used for alcoholism. The latter is an antidepressant and smoking cessation medication.

Some outside experts said they would like to see longer-term data beyond the trial’s 12 weeks to see what lasting benefits the medications provide. And Ayana Jordan, an addiction psychiatrist at Yale University, said she would have liked to see more information about different kinds of outcomes, such as whether the treatments improved people’s social connectedness or ability to work, even if they did not stop using meth entirely.

She also said that while it helps to have data indicating this combination treatment can help some people, the findings underscored the need for better medications that can help a greater swath of patients. “It’s easier to have a more optimistic perspective because we don’t have anything that works right now,” Jordan said.

Because scientists have not been able to develop treatments for methamphetamine addiction specifically, clinicians have turned to existing drugs to see what might provide some benefit. A 2019 clinical trial, for example, found that another antidepressant called mirtazapine helped some people reduce their meth use.

Doctors can prescribe drugs already approved by the Food and Drug Administration for other purposes “off-label” to try to treat methamphetamine addiction. But experts say having clinical trial data validates the approach and could also help convince payers to cover the medications.

In recent years, the country has started to grapple more with its addiction crisis, though much of the attention has been focused on opioids, which have caused the highest number of fatal overdoses. But quietly, overdose deaths from stimulants, including cocaine and methamphetamine, have been on the rise. In the 12-month period ending in June 2020, for example, there were more than 19,600 deaths from methamphetamine, according to preliminary federal data. In 2016, there were 6,700. (Many overdose deaths involve multiple drugs.)

The new clinical trial started with more than 400 patients who used meth regularly. In a first stage, the patients were randomized to receive either the medications or placebo. Then, those in the placebo group who did not respond initially were randomized again, either to stay on the placebo or to start the treatments. Taken together, 13.6% of people who were given the treatments in either round had at least three negative urine tests out of four taken at the end of the trial stages, versus 2.5% of people who were given placebos.

Men made up about two-thirds of participants. White people made up about 71% of participants, while 12% were Black and 13.6% identified as Latino or Hispanic.

The trial had a “number needed to treat” of nine, which means that nine patients would have to be given the medications in order for one to have a positive response. While that number might sound low, experts said the trial’s results are in the ballpark of the effectiveness of treatments for other types of addiction, like alcohol and tobacco. The exceptions, experts said, are methadone and buprenorphine, which have shown far higher levels of success in treating opioid use disorder.

One of the challenges of using naltrexone to treat opioid addiction is that, because of the way the medication works in the brain, people can’t have used opioids for several days before getting the injection. Otherwise, naltrexone can cause debilitating withdrawal symptoms.

But because methamphetamine interacts with the brain differently than opioids, people who use meth but not opioids should be able to be treated with naltrexone without having to wait, said Trivedi, who also consults for pharmaceutical companies, including Alkermes, the maker of Vivitrol.

Clinicians do not just rely on medications to treat addiction. Behavioral therapies like counseling are often involved as well. And with stimulants in particular, a practice called contingency management, which pays people or provides other rewards if they remain abstinent, has been shown to be effective.

Stefan Kertesz, an addiction medicine physician at the University of Alabama at Birmingham, who was not involved in the new clinical trial, said he could imagine offering the medication combination to patients who expressed a desire to stop using meth, while also recommending therapies like contingency management.

“This new trial suggests that for the people with methamphetamine use disorder who are beginning a very challenging process of recovery, a combination of medications can improve their chance of success,” Kertesz wrote in an email. “And that is promising.”