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For patients with schizophrenia, repetitive transcranial magnetic stimulation (rTMS) was effective and safe in treating auditory verbal hallucinations, according to a randomized sham-controlled trial.

A post-hoc analysis of a trial of 62 participants found that those who received active rTMS experienced a significantly greater reduction in Auditory Hallucination Rating Scale (AHRS) scores (difference 5.96, 95% CI 3.42-8.50, P<0.001) compared with those receiving sham treatment at 2 weeks, according to Gong-Jun Ji, PhD, of Anhui Medical University in Hefei, China, and co-authors.

These clinical effects were sustained at week 6 (group difference 7.89, 95% CI 4.77-11.01, P<0.001), and no serious adverse events were observed during the trial, they reported in .

Intention-to-treat analyses revealed significant time-by-group interactions for AHRS scores at week 2 and week 6 (P<0.001 for both), according to the authors.

They also noted that providing patients with a stronger TMS-induced electric field was associated with greater reductions in AHRS scores (P=0.002).

In the clinical setting, "rTMS with neuronavigation is an effective treatment for schizophrenia patients," Ji told 番茄社区 in an email, adding that "precise location of the target is quite important. To further improve clinical efficiency, the e-field induced by TMS should be optimized for each patient."

Ji noted that efficiency of rTMS treatment for auditory verbal hallucination symptoms has been mixed in previous trials. He added that one critical issue with many of those studies was imprecise locations for targeted stimulation.

"We overcome this limitation by using a neuronavigation system to monitor the spatial alignment between a given target and TMS coil during treatment," Ji said. "Thus, the take-home message is precise navigation is necessary to achieve significant efficiency of rTMS."

Ji noted that they also found significant alleviation in Positive and Negative Syndrome Scale (PANSS) scores during secondary analyses, even though the treatment protocol was only designed for auditory verbal hallucination symptoms.

Pritham Raj, MD, an associate professor of medicine and psychiatry at Oregon Health & Science University in Portland, told 番茄社区 that these findings are important because there is a need for alternative options to treat positive psychotic symptoms in individuals with schizophrenia.

"The fact that TMS has minimal adverse effects in general would be a tremendous boon to a population of patients that are used to challenging metabolic and movement disorders that often appear with pharmacotherapy," Raj said.

He added that he would like to see this trial run comparing the use of imaging and the use of standard measurement-based coil placement. He also noted another concern around rTMS as a treatment option is the high cost of delivery.

"Unless we make technologies, such as resting-state functional MRI mentioned in this study, cost-effective and accessible, we are only going to drive up the cost of delivering TMS and thus [make it] more cost-prohibitive overall," Raj said.

To conduct this 6-week, double-blind, sham-controlled, randomized clinical trial, the authors included 66 participants with both auditory verbal hallucination symptoms and schizophrenia from the Anhui Mental Health Center. The participants were recruited from September 2016 to August 2021.

There were 62 participants who completed treatment for 2 weeks. Among those individuals, 53% were women and mean age was 27.4 years.

Participants were randomized to an active rTMS group (n=32) and a sham treatment group (n=30). For the rTMS treatment, participants received three daily sessions for 2 weeks using a 70-mm air-cooled figure-of-8 coil. The sham treatment was delivered using equipment that was identical in appearance, but only generated sound and sensation on the participants' scalp but no current.

The authors noted that there was no statistically significant difference between groups in terms of how many correctly guessed their treatment group.

Major limitations included that this was a single-center trial with a small sample size and that a longer follow-up period is needed to determine how long the treatment effect lasted. The authors also noted that they did not test the effects of the treatment on cognitive function during the trial.

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