Efficacy of Slow Repetitive Transcranial Magnetic Stimulation in the Treatment of Resistant Auditory Hallucinations in Schizophrenia: A Meta-Analysis

André Aleman, Ph.D.; Iris E. Sommer, M.D., Ph.D.; and René S. Kahn, M.D., Ph.D.

Objective: Slow repetitive transcranial magnetic stimulation (rTMS), at a frequency of 1 Hz, has been proposed as a treatment for auditory hallucinations. Several studies have now been reported regarding the efficacy of TMS treatment, but results were inconsistent. Therefore, meta-analytic integration of the published trials is needed to evaluate the prospects of this new treatment.

Data sources: A literature search was conducted using PubMed and Web of Science for the years 1966 until February 2006. We used the search terms transcranial magnetic stimulation, TMS, rTMS, and hallucination*.

Study selection: From 15 treatment studies published since 1999, ten were sham-controlled trials and provided sufficient valid information to be included. All studies targeted the left temporoparietal cortex using 1 Hz rTMS.

Data extraction: Standardized mean gain effect sizes of real rTMS versus sham rTMS were computed based on pretreatment-posttreatment comparisons (computed from mean and SD values or t or F statistics).

Data synthesis: After calculation of treatment gain on hallucination ratings using standardized mean differences (sham vs. active rTMS), a mean weighted effect size was computed in the random effects model. We observed a significant mean weighted effect size for rTMS versus sham across the 10 studies, involving 212 patients, d = 0.76 (95% CI = 0.36 to 1.17). When only studies were included that used continuous stimulation (9 studies), the mean effect size increased to d = 0.88 and heterogeneity disappeared. There was no significant effect of rTMS on a composite index of general psychotic symptoms.

Conclusions: The results of this meta-analysis provide evidence for the efficacy of rTMS as an intervention that selectively alters neurobiologic factors underlying auditory hallucinations.

(J Clin Psychiatry 2007;68:416-421)

Received March 31, 2006; accepted July 19, 2006. From the BCN Neuroimaging Center, University Medical Center Groningen, University of Groningen (Dr. Aleman); and the Department of Psychiatry, University Medical Center Utrecht (Drs. Sommer and Kahn), the Netherlands.

The authors report no financial or other relationship relevant to the subject of this article.

Corresponding author and reprints: André Aleman, Ph.D., BCN Neuroimaging Center, A. Deusinglaan 2, 9713AW Groningen, the Netherlands (e-mail: A.aleman@med.umcg.nl).