Optimal rTMS for Cognitive Deficits and Negative Symptoms in Schizophrenia

Optimizing Treatment Protocol of High Frequency Repetitive Transcranial Magnetic Stimulation for Cognitive Deficits and Negative Symptoms in Schizophrenia: an Exploratory Study

Negative symptoms and cognition decline are major challenges in clinical management of schizophrenia. Dorsomedial prefrontal cortex (DLPFC) has been highly involved in the mechanisms of negative symptoms and cognitive symptoms of schizophrenia. However, the effect of repetitive transcranial magnetic stimulation (rTMS) over left or bilateral DLPFC has not yet been well studied. The aim of this study is to describe how the effectiveness of rTMS over different targets for cognitive deficits and negative symptoms in schizophrenia will be evaluated. The study will provide evidence to determine whether a bilateral DLPFC rTMS and is more effective than a left DLPFC rTMS alone to optimize treatment protocol in schizophrenia.

The study will be a randomized, double-blind trial comparing active rTMS over bilateral DLPFC vs. active rTMS over left DLPFC vs. sham rTMS delivered over DLPFC an 4-week treatment period. After assessment and inclusion into the study, participants will be randomized to receive up to 20 sessions of either active rTMS over left DLPFC or bilateral DLPFC or placebo treatments.

Inclusion Criteria:

• Met the Diagnostic and Statistical Manual of Mental Disorders, Five Edition (DSM-V) diagnostic criteria for schizophrenia and the diagnosis was verified by an experienced psychiatrist based on the Mini-International Neuropsychiatric Interview (MINI) 7.0 .
• Age between 18 and 60.
• Patients with prominently negative symptoms, which was defined as: PANSS negative subscore≥15 points and one of items N1-N7 scoring≥4.
• All patients were in stable clinical conditions (reduction rate of PANSS score<10% within 4 weeks), stable antipsychotic treatment for at least 4 weeks, and able to provide informed consent.

Exclusion Criteria:

• Any contraindication for rTMS (e.g., intracranial metal, pacemakers, cochlear and intracranial hypertension).
• Unstable clinical condition (e.g., being aggressive and uncooperative).
• Current substance abuse.
• Any other psychiatric diagnosis.
• Significant medical condition including neurological disease, severe cardiovascular, hepatic, renal diseases.
• Previous treatment with modified electric convulsive therapy (MECT) within 3 months before enrollment.