Repetitive Transcranial Magnetic Stimulation for Refractory Auditory Hallucinations in Schizophrenia

Study Overview
=================
Brief Summary
-----------------
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).

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

Conditions
-----------------
Refractory Schizophrenia

Intervention / Treatment
-----------------
* Device: repetitive Transcranial Magnetic Stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low frequency left (LFL) sided rTMS<br>LFL rTMS was administered at an intensity of 115% resting motor threshold at 1HZ for 20 minutes. The treatment targeted the left temporoparietal cortex (TPC). | Device: repetitive Transcranial Magnetic Stimulation<br>* The treatment involves the administration of a magnetic field applied to a specific area of the brain.<br>* Other names: Magstim Rapid (Magstim Company Ltd., Wales, UK);|
| Experimental: Priming stimulation<br>Priming stimulation was administered as follows: 10 minutes of 6 Hz at 90% resting motor threshold (RMT) administered to the left temporoparietal cortex followed by 10 minutes of 1 Hz stimulation at 115% RMT. | Device: repetitive Transcranial Magnetic Stimulation<br>* The treatment involves the administration of a magnetic field applied to a specific area of the brain.<br>* Other names: Magstim Rapid (Magstim Company Ltd., Wales, UK);|
| Sham Comparator: Sham Control<br>Sham stimulation was applied with identical parameters to those for the LFL condition but with the coil angled at 90 degrees off the scalp in a single wing tilt position. | Device: repetitive Transcranial Magnetic Stimulation<br>* The treatment involves the administration of a magnetic field applied to a specific area of the brain.<br>* Other names: Magstim Rapid (Magstim Company Ltd., Wales, UK);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychotic Symptoms Rating Scale (PSYRATS) | The primary outcome for this study was response (dichotomous outcome), defined as a 30 percent reduction in the composite score derived from the frequency, duration, loudness and content items of the hallucinations subscale of the Psychotic Symptoms Rating Scale (PSYRATS) | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Symptom Scale - Global | response on the global PANSS (30% reduction), PANSS global scale change | 4 weeks | 
| Positive and Negative Symptom Scale - Positive subscale | response on the positive scale of the PANSS (30% reduction), PANSS positive scale change | 4 weeks | 
| Hallucination Change Scale | response on the HCS (score < 5) | 4 weeks | 
| Auditory Hallucination Rating Scale (AHRS) | response on the AHRS and change over time in the AHRS. | 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hallucinations, Schizophrenia