REVIEW OF: Miuli A et al, World J Psychiatry 2021;11(8):477–490

STUDY TYPE: Literature review and meta-analysis

Some treatments for depression, particularly antidepressants, present risk of manic reactions, but whether this risk exists with transcranial magnetic stimulation (TMS) is less clear.

A group in Italy searched the world’s literature for studies using TMS for mood disorders. They sought studies that were double blind or single blind and published in English to find reports of manic and hypomanic switching.

The authors found 25 studies (21 double blind and four single blind) with a total of 576 subjects in active treatment and 487 receiving sham treatment. The studies used a variety of TMS protocols, but the most common was administered over the left dorsolateral prefrontal cortex for two weeks at 10 Hz with 2000–3000 pulses per session. Only eight studies reported on adverse effects like manic switching. Of those, four reported manic or hypomanic switches—three in active treatment and one in sham. Although there was a trend toward switches, the difference was not statistically significant, leading the authors to conclude that TMS does not seem to increase the risk of these reactions.

The parameters of TMS can be opaque to those of us who are not fluent in electricity, so we sought out Mark S. George, MD, one of the founding fathers of TMS (George MS et al, Neuroreport 1995;6(14):1853–1856) and editor-in-chief of the journal Brain Stimulation. Dr. George was hesitant to embrace the authors’ conclusion from this analysis.

He noted that the usual length of treatment is four to six weeks, so the majority of the studies reviewed here were underdosed at only two weeks. Furthermore, many of the studies used a gentler form of TMS with low-intensity pulses. More recent TMS protocols have raised the frequency of the magnetic pulse to produce faster results, a change that—in theory—could also raise the risk of mania.

CARLAT TAKE

This study provides some reassurance that TMS does not cause manic switching. However, many of the studies were underdosed, and few systematically looked for side effects. For all intents and purposes, this analysis does not answer the question.