Repetitive Transcranial Magnetic Stimulation for Negative Symptoms of Schizophrenia: Review and Meta-Analysis

Background: Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a treatment for the negative symptoms of schizophrenia. During the past
decade, several trials have reported on the efficacy of rTMS treatment; however, the results were inconsistent.

Objective: To assess the efficacy of prefrontal rTMS for treating negative symptoms of schizophrenia.

Data Sources: A literature search was performed in PubMed, ISI Web of Science, and EMBASE for the years 1985 through July 2008. The search terms used (language not specified) were "transcranial magnetic stimulation," "negative symptoms," and "schizophrenia." A cross-reference search of eligible articles was performed to identify studies not found in the computerized search.

Study Selection: Studies selected were randomized controlled trials assessing the therapeutic efficacy of prefrontal rTMS for negative symptoms in schizophrenia.

Data Extraction: Effect sizes (Cohen d) of each study were calculated. The overall standardized mean difference was calculated under a random effects model with 95% confidence intervals.

Data Synthesis: Nine trials, involving 213 patients, were included in the meta-analysis. The overall mean weighted effect size for rTMS versus sham was in the small-to-medium range and statistically significant (d‘ ‰=‘ ‰0.43; 95% CI, 0.05-0.80). When including only the studies using a frequency of stimulation of 10 Hz, the mean effect size increased to 0.63 (95% CI, 0.11-1.15). When including only the studies requiring participants to be on a stable drug regimen before and during the study, the mean weighted effect size decreased to 0.34 (95% CI, 0.01-0.67). Studies with a longer duration of treatment (≥‘ ‰3 weeks) had a larger mean effect size when compared to studies with a shorter treatment duration: d‘ ‰=‘ ‰0.58 (95% CI, 0.19-0.97) and d‘ ‰=‘ ‰0.32 (95% CI, −0.3 to 0.95), respectively.

Conclusions: The results of this meta-analysis warrant further study of rTMS as a potential treatment of negative symptoms of schizophrenia.

J Clin Psychiatry

Submitted: October 17, 2008; accepted January 2, 2009.

Online ahead of print: February 23, 2010.

Corresponding author: Jozarni J. Dlabač-de Lange, MD, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands ([email protected]).