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Ralph E. Hoffman, MD; Keith A. Hawkins, PsyD; Ralitza Gueorguieva, PhD; Nash N. Boutros, MD; Fady Rachid, MD; Kathleen Carroll, PhD; John H. Krystal, MD

Arch Gen Psychiatry. 2003;60:49-56.

Background  Neuroimaging studies suggest that auditory hallucinations (AHs) of speech arise, at least in part, from activation of brain areas underlying speech perception. One-hertz repetitive transcranial magnetic stimulation (rTMS) produces sustained reductions in cortical activation. Recent results of 4-day administration of 1-Hz rTMS to left temporoparietal cortex were superior to those of sham stimulation in reducing AHs. We sought to determine if a more extended trial of rTMS could significantly reduce AHs that were resistant to antipsychotic medication.

Methods  Twenty-four patients with schizophrenia or schizoaffective disorder and medication-resistant AHs were randomly allocated to receive rTMS or sham stimulation for 9 days at 90% of motor threshold. Patients receiving sham stimulation were subsequently offered an open-label trial of rTMS. Neuropsychological assessments were administered at baseline and during and following each arm of the trial.

Results  Auditory hallucinations were robustly improved with rTMS relative to sham stimulation. Frequency and attentional salience were the 2 aspects of hallucinatory experience that showed greatest improvement. Duration of putative treatment effects ranged widely, with 52% of patients maintaining improvement for at least 15 weeks. Repetitive transcranial magnetic stimulation was well tolerated, without evidence of neuropsychological impairment.

Conclusions  These data suggest that the mechanism of AHs involves activation of the left temporoparietal cortex. One-hertz rTMS deserves additional study as a possible treatment for this syndrome.

From the Department of Psychiatry, Yale University School of Medicine (Drs Hoffman, Hawkins, Gueorguieva, Boutros, Rachid, Carroll, and Krystal), Yale–New Haven Psychiatric Hospital (Dr Hoffman), Connecticut Mental Health Center (Drs Hawkins, Gueorguieva, Rachid, Carroll, and Krystal), and West Haven VA Medical Center (Drs Boutros, Carroll, and Krystal), New Haven, Conn.

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