Accelerated Transcranial Magnetic Stimulation Shows Promise for Methamphetamine Use Disorder and Depression

An accelerated course of repetitive transcranial magnetic stimulation (TMS) shows potential for treating co-occurring methamphetamine use disorder and depression, according to early data from a small feasibility trial.

The protocol involved 10-minute sessions of intermittent theta burst stimulation (iTBS) spaced at least 50 minutes apart, totaling 50 sessions over three weeks. Prior to each session, participants viewed images designed to induce craving.

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

Cue-induced craving showed minimal change. However, after the fourth iTBS session of the day, participants reported an improved ability to resist methamphetamine use, Jha noted.

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

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

“In less than a decade, overdose deaths involving methamphetamine have increased nearly six- to sevenfold,” Jha observed. “While overall overdose trends have dipped due to declines in opioid-related deaths, fatalities attributed solely to stimulants — including methamphetamine and cocaine — continue to rise. The problem is particularly acute in the western United States, in states such as Arizona, New Mexico, and California.”

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

No FDA-approved treatments exist for methamphetamine use disorder, Jha pointed out. Current guidelines from the American Society of Addiction Medicine and the American Academy of Addiction Psychiatry recommend no medications with high confidence for stimulant use disorder.

A 2021 randomized trial found that a combination of extended-release naltrexone (Vivitrol) and bupropion (Wellbutrin) modestly reduced drug use in people with methamphetamine use disorder: 13.6% of treated participants had negative urine samples at six weeks, versus 2.5% in the placebo group.

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

Conventional repetitive TMS typically involves one session daily, five days a week, for six to eight weeks. A prior trial assessing repetitive TMS for stimulant use disorder found that only 43.9% of participants assigned to treatment attended at least 20 of 30 sessions, he noted.

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

The primary outcome was feasibility, defined as completion of at least 30 of 50 accelerated repetitive TMS sessions — a protocol adapted from the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol for treatment-resistant depression.

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

“We collected daily EEG data, but one limitation was ending follow-up just one week after treatment,” he noted. “These individuals often have unstable circumstances, making longer follow-up — one to three months — challenging, so we kept the study small.”

Nevertheless, the findings demonstrate that an accelerated protocol can be feasibly tested in this population.

“Over the past two years, we screened 28 individuals and enrolled 23. Of those, three had cocaine use disorder and 20 had methamphetamine use disorder; all but one completed 45 or more sessions,” Jha said.

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

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