A study published Wednesday in JAMA Psychiatry showed that a drug used for depression, mirtazapine, could be effective in treating methamphetamine use disorder.
The phase 2a placebo-controlled clinical trial took place between 2013 and 2017 at an outpatient research clinic in San Francisco. Participants were all sexually active adults, and included cisgender men and transgender women, all who have sex with men. All 120 participants had methamphetamine use disorder and were actively using meth when starting the trial. They were given either 30 mg of mirtazapine daily, or a placebo, for 36 weeks. They were also given weekly counseling. Researchers found a significant decrease in methamphetamine in the urine samples of participants on mirtazapine at all three of the time markers. And there were no serious side effects among the mirtazapine users.
The trial built on a smaller study, which also showed mirtazapine significantly reducing meth use in those who took it, according to the San Francisco trial’s author, Phillip Coffin, M.D., M.I.A., director of substance use research in the Center for Public Health Research at the San Francisco Department of Public Health.
“Mirtazapine is unique among antidepressants, because it affects more than one neurotransmitter system and is not known to cause too much serotonin in the system,” Coffin said.
Right now, there are no Food and Drug Administration (FDA)–approved medications to treat meth addiction. Coffin said that, with further research showing similar results, mirtazapine could eventually be prescribed “off label” by doctors for methamphetamine use disorder, though he admits FDA approval might take a long time. Other drugs have been approved by the FDA for use disorders, including naltrexone (Vivitrol) for alcohol abuse and opioid addiction, and buprenorphine and methadone, also for opioid addiction. Coffin added that mirtazapine has been used for more than two decades, and many doctors know the drug and its side effects.
Meth use is associated with increased risk of heart attack, stroke, psychosis, and depression, and it also increases the risk of transmitting HIV and the hepatitis C virus. According to the National Survey on Drug Use and Health, 1.6 million Americans in 2017 used meth at least once that year.
In addition to looking at meth use for participants using mirtazapine, Coffin and his team also examined a secondary outcome—sexual risk behavior—and found that those who adhered to mirtazapine for at least 24 weeks had significantly reduced sexual risk factors, including fewer sexual partners and fewer episodes of anal sex without a condom. But Coffin said there was no analysis of whether decreasing meth use itself caused the reduction in riskier sexual behavior. He also admits that it is unclear how the weekly counseling in the study affected outcomes. “It may be synergistic in that the addition of mirtazapine may amplify the effects of counseling, or the other way around.” Or the counseling may have had no effect, Coffin said, pointing to studies of other drugs tested for different substance use disorders. “Buprenorphine plus counseling has shown to have the same outcome as buprenorphine alone, for opioid use disorder,” he said.
Torie Sepah, M.D., a doctor who specializes in psychiatry at AltaMed Health’s integrated primary and HIV care program in Los Angeles, said she found Coffin’s study “elegant” in how it looked at the drug’s effect on meth use and on sexual behavior of a vulnerable population, and that it “sets a good precedent for further research.”
Sepah, who treats HIV-positive clients suffering from addictions, said that meth use increases high-risk behaviors. “There is a lot of harm that comes from decisions made while using meth. There is grandiosity, and people don’t think long-term. Meth use can also reduce adherence for [HIV-positive] people on meds.”
Sepah said that more studies of why people become addicted to methamphetamine are needed. It’s well known that meth is highly addictive, due to its rapid onset and peak and the “reward pathways” that have the brain constantly craving for more of the high. But Sepah said that, in addition to some younger gay men who use meth as a party drug and end up getting hooked, some of the addicted patients she sees are using meth for greater “functional utility.”
“I see many gay men who didn’t use meth until their 40s, and they say they started because they were feeling tired all the time, or they had low testosterone or reduced sexual function and thought [meth] would help,” she said.
Sepah also said that younger patients tended to seroconvert while on meth, while older ones tended to start using meth while they were positive. “There is a challenge for a population that has been HIV positive for a long time, in that the cumulative damage done to the brain in cognition can’t be undone even when a person is virally suppressed,” she continued. “HIV-positive patients who are older say meth helped them with cognition.” Though, she added, it’s unclear whether it actually helped them or just made them feel like their brains were working more effectively.
Also unclear, Coffin said, was whether secondary indications for mirtazapine could have led to a decrease in meth use among study participants. “Mirtazapine also helps people sleep, and a lot of meth use happens at night. Possibly mirtazapine is helping people reduce meth use by letting them sleep.”
Finally, it’s not clear whether mirtazapine, if indicated for curbing meth addiction, would be used long-term, or just to help a person get clean. Coffin said he plans to further study the drug and its possible use in treating meth use disorder.