Repetitive Transcranial Magnetic Stimulation for Refractory Auditory Hallucinations in Schizophrenia

A Randomized Double-Blind Sham-Controlled Trial of Transcranial Magnetic Stimulation for Refractory Auditory Hallucinations in Schizophrenia

Studies using repetitive transcranial magnetic stimulation (rTMS) as a treatment for refractory auditory hallucinations (AH) in schizophrenia have shown promise. The majority of studies have examined the effect of low frequency left-sided stimulation (LFL) (i.e., 1 Hz) to the temporal parietal cortex (TPC). Priming stimulation (6 Hz) prior to LFL stimulation (hereby simply referred to as priming) has been shown to enhance the neurophysiological effects of LFL rTMS alone and, as such, may lead to greater attenuation of AH. Therefore, this study evaluated the efficacy of priming rTMS and LFL rTMS, compared to sham, applied to the TPC in patients with schizophrenia experiencing refractory auditory hallucinations (AH).

Inclusion Criteria:

• voluntary and capable to consent based on the subject's ability to provide a spontaneous narrative description of the key elements of the study
• have a diagnosis of Schizophrenia or Schizoaffective Disorder as confirmed by the Structured Clinical Interview for the DSM-IV (SCID-IV)
• between the ages of 18 and 65
• meet criteria for AH of at least moderate severity based on the Positive and Negative Symptom Scale (PANSS)
• willing to keep the dose of antipsychotic stable for the duration of the study
• meet criteria for medication resistance, defined as daily AH despite 2 adequate 6-week trials of at least 2 antipsychotic medications and including 1 atypical antipsychotic medication. An adequate trial is defined as a daily dose of 1000 chlorpromazine equivalents for typical antipsychotics medications and the following dosages for atypical antipsychotic medications: risperidone 6 mg, olanzapine 15 mg, quetiapine 500 mg, clozapine 300 mg.

Exclusion Criteria:

• DSM-IV history of alcohol and/or substance abuse in past month, or alcohol and/or substance dependence in the last 6 months
• presence of concomitant major, unstable medical or neurologic illness, or a history of seizures
• are pregnant
• have received rTMS for any reason in the past
• have had a dose change of usual psychotropic medications in the 4 weeks preceding study entry.