Meth Use Disorder May Benefit From Accelerated Transcranial Magnetic Stimulation

An accelerated course of repetitive transcranial magnetic stimulation (TMS) hinted at the potential to treat co-existing methamphetamine use disorder and depression, early data from a small feasibility trial suggested.

The protocol included 10-minute sessions of intermittent theta burst stimulation (iTBS) at least 50 minutes apart for a total of 50 sessions over 3 weeks. Before each session, participants were presented images (cues) to induce craving.

After 12 visits, participants showed reductions in self-reported methamphetamine craving and overall depression severity, reported Manish Jha, MBBS, of UT Southwestern Medical Center in Dallas, at the American Society of Functional Neuroradiology meeting in Newport Beach, California.

There was little change in craving for methamphetamine after participants received a cue. After the fourth iTBS session of the day, participants reported improvements in their ability to resist using methamphetamines, Jha said.

“We didn’t see much change in cue-induced craving,” Jha said. “What did change a bit was the self-reported craving and how much they were craving currently in the moment before the cue craving. So, there may be some signal.”

The study shows the feasibility of using accelerated iTBS to treat methamphetamine use disorder, Jha noted.

“In less than a decade, overdose deaths involving methamphetamine have increased almost 6- to 7-fold,” Jha observed. “The trend has been going down because of the reduction in opioid-involved overdose deaths, but the number of deaths attributable just to stimulants — including methamphetamine and cocaine — has continued to increase. It’s more of a problem in the western United States, in states like Arizona and New Mexico, and in California, also.”

The prevalence of methamphetamine use disorder in the U.S. also has risen in the past decade, he added.

There are no FDA-approved treatments to treat methamphetamine use disorder, Jha pointed out. No medications are recommended with high confidence in guidelines for treating stimulant use disorder from the American Society of Addiction Medicine and the American Academy of Addiction Psychiatry, he added.

In 2021, a randomized trial showed that a combination of extended-release naltrexone (Vivitrol) and bupropion (Wellbutrin) modestly reduced drug use among people with methamphetamine use disorder, with 13.6% of participants who received treatment showing negative urine samples after 6 weeks, compared with 2.5% of the placebo group.

“Still, there is really an urgent need to develop newer treatments,” Jha said.

A conventional pattern for repetitive TMS has been one session a day, 5 days a week, for 6 to 8 weeks, he noted. A previous trial that evaluated the feasibility of repetitive TMS for stimulant use disorder showed that only 43.9% of participants randomized to a treatment group attended at least 20 of 30 sessions, he said.

Jha’s open-label trial included people diagnosed with moderate or severe cocaine or methamphetamine use disorder determined by the Mini-International Neuropsychiatric Interview (MINI). Participants also had a Patient Health Questionnaire-9 (PHQ-9) score of at least 5 (PHQ-9 scores can range from 0 to 27, with higher scores indicating more depression severity).

The primary outcome of the study was feasibility, measured by completion of at least 30 of 50 sessions of repetitive TMS that used an accelerated course which borrowed elements from the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol for treatment-resistant depression.

Of 20 participants with methamphetamine use disorder, 94.7% completed at least 45 sessions, Jha reported. The mean number of sessions was 46.3.

“We did some EEG [electroencephalography] work every day as they were coming in, but probably one of the mistakes we made in this protocol was ending our follow-up 1 week after the treatment,” he noted. “These individuals have pretty unstable lives, and trying to follow them for a month or 3 months is difficult, so we just designed this as a small study.”

The findings show, however, that an accelerated protocol can be tested in this population.

“In the past 2 years, we screened 28 people, and 23 people were enrolled. Of those, three people had cocaine use disorder, 20 people had methamphetamine use disorder, and everyone except one person completed 45 or more sessions,” Jha said.

A multisite randomized controlled trial is needed to replicate and expand these findings, he added.