Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Negative Symptoms in Schizophrenia

Study Overview
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Brief Summary
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Schizophrenia is a major psychotic disorder that presents an enormous burden to the patients and their relatives. Despite treatment with second generation antipsychotics, negative symptoms and cognitive impairment often persist and determine an unfavourable course including reduction in life quality. Prefrontal repetitive transcranial magnetic stimulation (rTMS), a promising noninvasive biological technique, applied adjuvant to ongoing antipsychotic treatment was demonstrated to be safe and was associated with improvement in negative symptoms in the majority of the small placebo-controlled trials. The primary objective of the trial is to investigate the efficacy of high-frequency rTMS (add-on to antipsychotic therapy) in the treatment of negative symptoms in schizophrenia compared to sham stimulation (placebo).

Official Title
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Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Negative Symptoms in Schizophrenia - a Multicenter Study

Conditions
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Schizophrenia

Intervention / Treatment
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* Other: Repetitive transcranial magnetic stimulation
* Other: Sham repetitive transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female in-patients and out-patients, 18 - 60 years of age Diagnostic criteria for schizophrenia according to ICD-10/DSM IV PANSS negative sum score > 20 points, 1 of items N1 - N7 (range 1 to 7) ≥ 4 (at least moderate) Improvement in PANSS negative sum score less than 10 % in the last 2 weeks prior to study entry, stable antipsychotic medication Informed Consent Exclusion Criteria: Clinically relevant psychiatric comorbidity, verbal IQ < 85 History of epileptic seizures, organic brain disease Instable medical comorbidity or condition Previous treatment by rTMS Factors not compatible with the use of TMS, e.g. cardiac pace makers or other metallic implants, pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>10 Hz rTMS of left dorsolateral prefrontal cortex (DLPFC) (15 sessions/3 weeks, 1000 stimuli per session, stimulation intensity 110 % related to the individual resting motor threshold). | Other: Repetitive transcranial magnetic stimulation<br>* 10 Hz rTMS of left dorsolateral prefrontal cortex (DLPFC) (15 sessions/3 weeks, 1000 stimuli per session, stimulation intensity 110 % related to the individual resting motor threshold); in total 15.000 stimuli.<br>|
| Sham Comparator: 2<br>placebo (sham)-rTMS of left DLPFC (15 sessions/3 weeks, 1000 stimuli per session) | Other: Sham repetitive transcranial magnetic stimulation<br>* placebo (sham)-rTMS of left DLPFC (15 sessions/3 weeks, 1000 stimuli per session; in total 15.000 stimuli<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in negative symptoms (baseline vs. day 21, PANNS negative sum score) |  | 105 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy on cognition, EPS, neuroplasticity (sMRI/MRS), depression, life quality and social function |  | 105 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, negative symptoms, TMS, magnetic stimulation