Efficacy of High-Frequency Repetitive TMS on Schizophrenia Symptoms

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brain network
Investigators examined the effects prefrontal rTMS on negative symptoms vs sham rTMS.

High-frequency repetitive transcranial magnetic stimulation (rTMS) produces the same level of symptom improvement as sham rTMS for patients with schizophrenia who have predominantly negative symptoms, according to a study published in Psychiatry Research.

The negative symptoms of schizophrenia—eg, poverty of speech, flattened emotional response, social withdrawal, and lack of initiative and pleasure—greatly contribute to the disease-associated burden. The current study sought to re-analyze data from the rTMS for the Treatment of Negative Symptoms in Schizophrenia (RESIS) trial, by using the 2-factor negative symptom model of the Positive and Negative Syndrome Scale (PANSS). This semi-structured diagnostic interview can be used to assess the 3 subdomains of schizophrenia symptoms—Negative symptoms (7 items), Postitive symptoms (7 items), and General Pathology (16 items)—in relation to one another.

The RESIS trial assigned 157 patients to either active rTMS treatment (n=76), or sham rTMS treatment (n=81). Participants were assessed with PANSS at baseline, and again after receiving 5 active or sham rTMS treatments a week for 3 weeks. The findings of the original RESIS trial indicated that the active rTMS treatments were not superior to the sham treatments, and the current study’s re-analysis confirmed these findings after using the 2-factor negative symptom model of PANSS to disentangle the specific outcomes for different negative symptoms.

Although the active and sham treatments showed an equal effect, both treatment groups showed significant improvements in negative symptoms. Study investigators speculate that the regular social stimuli of the trial protocol had sufficient impact on participants that whatever effect the active rTMS may have had on negative symptoms became negligible after statistical analyses.

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Study investigators conclude that, “Future trials should implement and combine more specific assessments for negative symptoms like the BNSS (Kirkpatrick et al., 2011), CAINS (Kring et al., 2013), SANS (Andreasen, 1982) or use reliable PANSS factors beyond the established PANSS subscales to stratify inclusion criteria and outcome as recently shown in pharmaceutical research (Nemeth et al., 2017).”


Hansbauer M, Wobrock T, Kunze B, et al. Efficacy of high-frequency repetitive transcranial magnetic stimulation on PANSS factors in schizophrenia with predominant negative symptoms – results from an exploratory re-analysisPsychiatry Res. 2018; 263:22-29.