TMS Promising for Methamphetamine Withdrawal

Batya Swift Yasgur, MA, LSW

September 14, 2018

Repetitive transcranial magnetic stimulation (rTMS) may reduce drug cravings and withdrawal symptoms in individuals addicted to methamphetamine, new research suggests.

Investigators compared the use of real rTMS to sham rTMS in 48 adult men who were experiencing withdrawal symptoms during discontinuation of use of methamphetamine.

They found significant decreases in withdrawal symptoms and cravings and improvements in quality of sleep and mood after 10 days of rTMS treatments, compared to sham treatment.

"We found that noninvasive brain stimulation, especially transcranial magnetic stimulation, could alleviate the withdrawal symptoms in methamphetamine dependents," senior author Ti-Fei Yuan, PhD, MPhil, of Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong, University School of Medicine, China, told Medscape Medical News.

"The withdrawal symptoms decreased rapidly, and sleep quality and mood status improved significantly," he said.

The study was published online September 12 in JAMA Psychiatry.

Few Effective Treatments

"Addiction is a worldwide problem, with relapse often caused by craving for the drug or getting rid of the aversive withdrawal symptoms," Yuan said.

An array of neurologic factors contribute to withdrawal, including the action of neurotransmitters, neuropeptides, and signal transduction pathways. Several brain regions have been implicated in withdrawal symptoms during abstinence from addictive drugs, the authors note.

"Currently, there are only a few drugs that alleviate withdrawal symptoms," Yuan noted.

Stimulation of the thalamic-accumbens dopamine D2 medium spiny neuron pathway has been shown to alleviate somatic signs induced by opiate withdrawal in an animal model, but it is unknown whether noninvasive brain stimulation could "facilitate detoxification during the withdrawal period in humans," the authors state.

To investigate the effectiveness of this technique, the researchers used rTMS that targeted the left dorsal-lateral prefrontal cortex (DLPFC) to "modulate symptoms of withdrawal from methamphetamine."

The randomly allocated 48 men who were experiencing withdrawal symptoms after methamphetamine abstinence (mean age, 33.3 years; range, 18 - 54 years; SD, 9.8 years) to receive either real rTMS (n = 24) or sham rTMS (n = 24).

Participants reported no history of head trauma, epilepsy, heart diseases, or metal implants in the body.

To evaluate withdrawal symptoms, the researchers used a Chinese version of the Methamphetamine Withdrawal Symptom Scale. Sleep quality was measured using the Pittsburgh Sleep Quality Index, and depression and anxiety were evaluated using self-rating depression and anxiety scales.

A visual analogue scale was used to evaluate cue-induced cravings.

The study lasted for 12 days. rTMS (10 Hz for 10 min) targeting the left DLPFC was applied for 10 days, and the participants were given 2 days of rest after the first 5 days.

All Stages of Rehabilitation

No significant mean differences were found between the two groups in age, educational level, race, body mass index, length of abstinence, duration of methamphetamine use, or daily methamphetamine dose.

After 10 days of rTMS treatment, significant changes in withdrawal symptoms, craving, quality of sleep, and mood status were found.

Descriptive data showed that withdrawal symptoms decreased, with a significant difference for time (F3,32 = 198.18; P < .001; ηp2 = 0.81).

There was also a significant time × group interaction effect (F3,132 = 20.27; P < .001; ηp2 = 0.31). Post hoc t tests found that withdrawal symptoms were significantly reduced for both the rTMS group and the group that received sham treatment (t23 = 13.21; P < .001; and t21 = 9.53; P < 0.001 respectively).

For craving, the analysis showed a significant difference for time (F3,132 = 50.52; P < .001; ηp2 = 0.53) for craving. The descriptive data also showed that craving decreased.

Additionally, there was a significant time × group interaction effect (F3,132 = 22.93; P < .001; ηp2 = 0.34); post hoc t tests showed that the craving score was significantly reduced for the real rTMS group (t23 = 8.59; P < .001) vs the sham rTMS group (t21 = 2.40; P = .046) after applying Bonferroni correction for multiple comparisons.

Similar findings were obtained for quality of sleep. Significant reductions in sleep disturbances were found in the real rTMS group vs the sham treatment group (t23 = 8.85; P < .001 and t21 = 1.08; P = 0.29, respectively).

Both depression and anxiety followed a similar pattern, with significant reduction in depressive symptoms for the real rTMS group (t23 = 11.97; P < .001), compared to the sham rTMS group (t21 = 1.86; P = 0.08), as did reductions in symptoms of anxiety for the real rTMS group (t23 = 5.28; P < 0.001) vs the sham rTMS group (t21 = 2.35; P = .03).

The reduced craving score was correlated positively with reductions in withdrawal symptoms (r = 0.641; P < .001), improvements in sleep (r = 0.797; P < .001), and decreased severity of anxiety (r = 0.528; P < .01), but not for depression (r = 0.163; P = .44).

"To our knowledge, this study is the first effort to manage drug withdrawal using brain stimulation technique," Yuan commented.

"This [study finding] argues for the possibility to apply TMS to all stages of addiction rehabilitation — from early stage of withdrawal to middle stage of craving modulation, and to end stage of cognition recovery," he emphasized.

More Research Needed

Commenting on the study for Medscape Medical News, Ian Cook, MD, professor emeritus of psychiatry at the University of California, Los Angeles, and director, the Los Angeles TMS Institute, who was not involved with the study, called it a "well-done, albeit small study" that "addresses a very important tissue, in terms of how we help people getting off drugs of abuse."

He described the findings as "encouraging since they showed improvements in things like mood and craving and other things that tend to lead people to relapse."

He added that it is "probably a little early for clinicians to try it, but it certainly calls for others to try to replicate the study and its paradigm."

Yuan agreed, noting that "we are limited by available treatment protocols and frequencies, and this will not be done until more clinicians are trying."

He encouraged "more people to try and improve current TMS procedures," adding, "We sincerely wish to open collaboration with more international scientists and clinicians to improve the quality for our research."

The study was supported by National Natural Science Foundation of China. Dr Yuan, Dr Yuan's coauthors, and Dr Cook have disclosed no relevant financial relationships.

JAMA Psychiatry. Published online September 12 2018. Abstract

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