Should we treat auditory hallucinations with repetitive transcranial magnetic stimulation? A metaanalysis

Objective: Abnormal activations of neural networks implicated in auditory stimuli processing are hypothesized to generate auditory hallucinations (AH) in schizophrenia spectrum disorders. Because repetitive transcranial magnetic stimulation (rTMS) has the potential to modulate neural network activity, several studies have explored its use in treating medication-resistant AH, with mixed results in small-to-medium patient samples. Our aim is to apply a metaanalytic approach to exploring the efficacy of rTMS in treating medication-resistant AH. Method: A search of the electronic databases for studies comparing low-frequency (1 Hz) rTMS over the left temporoparietal cortex to sham stimulation in patients suffering from medication-resistant AH was performed. Our search was completed by cross-referencing the articles, searching the Current Controlled Trials website, and direct contact with relevant researchers. Results: From 265 possible abstracts, 6 parallel-arm, double-blind placebo-controlled and 4 crossover controlled trials, all randomized, matched the inclusion and exclusion criteria (n = 232). The primary outcome measure (effect of active treatment on AH at the end of the treatment) was tested with a random effect model and reached a significant homogeneous ES estimate (Hedges' g = 0.514; P = 0.001; 95CI%, 0.225 to 0.804; Q = 13.022; P = 0.162). Conclusions: We found that low-frequency rTMS over the left temporoparietal cortex has a medium ES action on medication-resistant AH. This result has implications for understanding the pathophysiology of psychotic symptoms (specifically AH) and supports the use of rTMS as a complementary treatment approach in patients suffering from treatment-resistant AH.