Efficacy of slow repetitive transcranial magnetic stimulation in the treatment of resistant auditory hallucinations in schizophrenia: A meta-analysis

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 I 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% Cl = 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.