Transcranial Magnetic Stimulation in Schizophrenia

To the Editor: Repetitive transcranial magnetic stimulation (rTMS) has been found to down-regulate serotonin 2 receptors in the frontal cortex (1) and increase the responsiveness of rats to dopaminergic stimulation (2), which suggests that rTMS may affect frontal cortex function and antagonize the dopaminergic-blocking adverse effects of typical antipsychotics in schizophrenia patients.

We investigated the effects of rTMS add-on treatment on the P300 event-related potential and hyperprolactinemia caused by typical antipsychotics. All subjects provided written informed consent. Five patients with chronic schizophrenia (two men and three women, mean age=33.2 years) treated with typical antipsychotics received 5 seconds of 10-Hz rTMS (20 times at 30-sec intervals) at the left dorsolateral prefrontal cortex for 5 consecutive days. Both P300 event-related potentials and serum prolactin levels were measured at baseline and 2 days after the last rTMS treatment. Ongoing antipsychotic medication treatment was not altered during the study periods.

Generally, treatment was well tolerated, and no serious adverse effects were reported. Three patients reported improvement in their mood after rTMS; no exacerbation of psychotic symptoms was found. The prolactin levels of all five patients decreased 24.4%–49.4% from their respective baseline levels after rTMS treatment. The difference in the mean prolactin levels before and after rTMS was significant (Wilcoxon’s signed-rank test: z=–2.02, p<0.05, two-tailed). Amplitudes of P300 at the Fz site were also significantly elevated after rTMS treatment (paired t=–4.08, df=4, p<0.02, two-tailed) and elevated at marginal significance at the Cz site (paired t=–2.61, df=4, p<0.06, two-tailed).

Our finding is in contrast with the results of a previous study of normal volunteers in which rTMS did not change serum prolactin levels (3). This discrepancy may be due to differences in rTMS method (e.g., frequency, location) or the study group source; our patients had antipsychotic-induced hyperprolactinemia. rTMS might enhance dopaminergic function (2), which may antagonize hyperprolactinemia because of dopaminergic blocking by typical antipsychotics.

Event-related potentials are thought to reflect neuroelectric activity related to cognitive processes, such as the allocation of attention and short-term memory to auditory stimuli (4). Our results suggest that rTMS may be used as an add-on therapy in patients taking antipsychotics to improve cognitive function and antagonize the adverse effects of hyperprolactinemia.