2021medRxivOpen access

The efficacy of transcranial magnetic stimulation (TMS) for negative symptoms in schizophrenia: A systematic review and meta-analysis

Rasmus Lorentzen, Tuan D. Nguyen, Alexander McGirr, Fredrik Hieronymus, Søren Dinesen Østergaard

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Abstract

Abstract Several trials have shown preliminary evidence for the efficacy of Transcranial Magnetic Stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here, we synthesize this literature in a systematic review and quantitative meta-analysis of double-blind randomized controlled trials of TMS in patients with schizophrenia. Specifically, MEDLINE, EMBASE, Web of Science, and PsycINFO were searched for sham-controlled, randomized trials of TMS among patients with schizophrenia. The standardized mean difference (SMD, Cohen’s d ) with 95% confidence intervals (CI) was calculated for each study (TMS vs. sham) and pooled across studies using an inverse variance random effects model. We identified 56 studies with a total of 2550 participants that were included in the meta-analysis. The pooled analysis showed statistically significant superiority of TMS (SMD=0.37, 95%CI: 0.23; 0.52, p-value <0.00001), corresponding to a number needed to treat of 5. Furthermore, stratified analyses suggested that TMS targeting the left dorsolateral prefrontal cortex, using a stimulation frequency >1 Hz, and a stimulation intensity at or above the motor threshold, was most efficacious. There was, however, substantial heterogeneity and high risk of bias among the included studies. In conclusion, TMS appears to be an efficacious treatment option for patients with schizophrenia suffering from negative symptoms, but the optimal TMS parameters have yet to be resolved.

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Abstract Several trials have shown preliminary evidence for the efficacy of Transcranial Magnetic Stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here, we synthesize this literature in a systematic review and quantitative meta-analysis of double-blind randomized controlled trials of TMS in patients with schizophrenia. Specifically, MEDLINE, EMBASE, Web of Science, and PsycINFO were searched for sham-controlled, randomized trials of TMS among patients with schizophrenia. The standardized mean difference (SMD, Cohen’s d ) with 95% confidence intervals (CI) was calculated for each study (TMS vs. sham) and pooled across studies using an inverse variance random effects model. We identified 56 studies with a total of 2550 participants that were included in the meta-analysis. The pooled analysis showed statistically significant superiority of TMS (SMD=0.37, 95%CI: 0.23; 0.52, p-value <0.00001), corresponding to a number needed to treat of 5. Furthermore, stratified analyses suggested that TMS targeting the left dorsolateral prefrontal cortex, using a stimulation frequency >1 Hz, and a stimulation intensity at or above the motor threshold, was most efficacious. There was, however, substantial heterogeneity and high risk of bias among the included studies. In conclusion, TMS appears to be an efficacious treatment option for patients with schizophrenia suffering from negative symptoms, but the optimal TMS parameters have yet to be resolved.

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Available abstract

Abstract Several trials have shown preliminary evidence for the efficacy of Transcranial Magnetic Stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here, we synthesize this literature in a systematic review and quantitative meta-analysis of double-blind randomized controlled trials of TMS in patients with schizophrenia. Specifically, MEDLINE, EMBASE, Web of Science, and PsycINFO were searched for sham-controlled, randomized trials of TMS among patients with schizophrenia. The standardized mean difference (SMD, Cohen’s d ) with 95% confidence intervals (CI) was calculated for each study (TMS vs. sham) and pooled across studies using an inverse variance random effects model. We identified 56 studies with a total of 2550 participants that were included in the meta-analysis. The pooled analysis showed statistically significant superiority of TMS (SMD=0.37, 95%CI: 0.23; 0.52, p-value <0.00001), corresponding to a number needed to treat of 5. Furthermore, stratified analyses suggested that TMS targeting the left dorsolateral prefrontal cortex, using a stimulation frequency >1 Hz, and a stimulation intensity at or above the motor threshold, was most efficacious. There was, however, substantial heterogeneity and high risk of bias among the included studies. In conclusion, TMS appears to be an efficacious treatment option for patients with schizophrenia suffering from negative symptoms, but the optimal TMS parameters have yet to be resolved.

Key concepts: Transcranial magnetic stimulation, Meta-analysis, Strictly standardized mean difference, Randomized controlled trial, Schizophrenia (object-oriented programming), PsycINFO, Dorsolateral prefrontal cortex, Publication bias

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