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. 2024 May 28:15:1377257.
doi: 10.3389/fpsyt.2024.1377257. eCollection 2024.

Placebo effects of repetitive transcranial magnetic stimulation on negative symptoms and cognition in patients with schizophrenia spectrum disorders: a systematic review and meta-analysis

Mingqi Wang  1 , Shensen Lu  1 , Lu Hao  1 , Yifei Xia  2 , Zhenchun Shi  1 , Lei Su  1
Affiliations

Placebo effects of repetitive transcranial magnetic stimulation on negative symptoms and cognition in patients with schizophrenia spectrum disorders: a systematic review and meta-analysis

Mingqi Wang et al. Front Psychiatry. .

Abstract

Background: Negative symptoms and cognitive impairments are highly frequent in schizophrenia spectrum disorders (SSD), associated with adverse functional outcomes and quality of life. Repetitive transcranial magnetic stimulation (rTMS) has been considered a promising therapeutic option in SSD. However, placebo effects of rTMS on these symptoms remained unclear.

Objective: To investigate placebo effects of rTMS on alleviating negative symptoms and cognitive impairment in patients with SSD and to explore potential moderators.

Methods: We systematically searched five electronic databases up to 15 July 2023. Randomized, double-blind, sham-controlled trials investigating effects of rTMS on negative symptoms or cognition in patients with SSD were included. The pooled placebo effect sizes, represented by Hedges' g, were estimated using the random-effects model. Potential moderators were explored through subgroup analysis and meta-regression.

Results: Forty-four randomized controlled trials with 961 patients (mean age 37.53 years; 28.1% female) in the sham group were included. Significant low-to-moderate pooled placebo effect sizes were observed for negative symptoms (g=0.44, p<0.001), memory (g=0.31, p=0.010), executive function (g=0.35, p<0.001), working memory (g=0.26, p=0.004), and processing speed (g=0.36, p=0.004). Subgroup analysis indicated that placebo effects were affected by sham stimulation methods, rTMS targeting approaches, and stimulation frequency.

Conclusions: Placebo effects of rTMS on negative symptoms and cognition in patients with SSD are significant in a small-to-moderate magnitude, which might be mediated by rTMS parameters. Our findings will provide new insights for practitioners to further optimize and establish standardized rTMS protocols for future RCTs tackling cardinal symptoms in SSD.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023390138.

Keywords: cognition; negative symptoms; placebo effects; randomized controlled trial; repetitive transcranial magnetic stimulation; schizophrenia spectrum disorders.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flow chart for literature review.
Figure 2
Figure 2
Placebo effects of rTMS on negative symptoms in patients with SSD.
Figure 3
Figure 3
(A) Placebo effects of rTMS on memory in patients with SSD. (B) Placebo effects of rTMS on executive functioning in patients with SSD. (C) Placebo effects of rTMS on working memory in patients with SSD. (D) Placebo effects of rTMS on attention in patients with SSD. (E) Placebo effects of rTMS on processing speed in patients with SSD.
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