This randomized controlled trial (RCT) is the first to evaluate the efficacy and safety of a multi-target TMS protocol targeting the right orbitofrontal cortex (R-OFC), left dorsolateral prefrontal cortex (L-DLPFC), and left inferior parietal lobule (L-IPL) for negative symptoms of schizophrenia.
Schizophrenia is a chronic and severe mental disorder. Although antipsychotic medications are effective for positive symptoms, they offer limited improvement for negative symptoms and cognitive deficits. Effective treatments for these symptoms are still lacking. To address current clinical bottlenecks, there is an urgent need to develop novel, effective treatment strategies. Repetitive transcranial magnetic stimulation (rTMS) is a recently developed neuromodulation technique. The latest evidence-based guidelines indicate that the level of evidence for rTMS in treating schizophrenia remains low (i.e., Level C evidence, possibly effective). However, the critical parameter of target selection has not received sufficient attention. This randomized controlled trial (RCT) is the first to evaluate the efficacy and safety of a multi-target TMS protocol targeting the Right Orbitofrontal Cortex (R-OFC), Left Dorsolateral Prefrontal Cortex (L-DLPFC), and Left Inferior Parietal Lobe (L-IPL) for negative symptoms of schizophrenia. MRI-guided neuronavigation will be used to localize targets in each subject. The intensity of TMS stimulations is set to 80-120% of resting motor threshold (RMT). A total of 50 TMS sessions will be administered. The stimulation sequence will be R-OFC (1 Hz) → L-DLPFC (iTBS) → L-IPL (iTBS). The first target (R-OFC) will receive 720 pulses at 1 Hz, while the second and third targets (L-DLPFC and L-IPL) will each receive 900 pulses of iTBS. Five sessions will be delivered per day for 10 consecutive working days, with a 60-minute interval between sessions. Clinical assessments, cognitive evaluations, and resting-state functional Magnetic Resonance Imaging (MRI) scans will be performed before and after TMS treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
64
Repetitive transcranial magnetic stimulation (rTMS) is a recently developed neuromodulation technique.
Shanghai Mental Health Center
Shanghai, Shanghai Municipality, China
Change in severity of negative symptoms before and after TMS intervention, i.e., change in Positive and Negative Syndrome Scale - Negative subscale (PANSS-N)
Schizophrenia negative symptoms assessed using Positive and Negative Syndrome Scale - Negative subscale (PANSS-N) Minimum value: 7 (each of the 7 items scored 1 = absent) Maximum value: 49 (each of the 7 items scored 7 = extreme) Higher score indicates: Worse outcome (greater severity of negative symptoms)
Time frame: Negative symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment.
Change in cognitive function scores before and after intervention
MATRICS Consensus Cognitive Battery (MCCB) total score and subtest scores
Time frame: MATRICS Consensus Cognitive Battery (MCCB) will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and 4 weeks ( Day 42) after completion of TMS treatment.
Change in positive symptom scores before and after intervention
Positive and Negative Syndrome Scale - Positive subscale (PANSS-P) Minimum value: 7 (each of the 7 items scored 1 = absent) Maximum value: 49 (each of the 7 items scored 7 = extreme) Higher score indicates: Worse outcome (greater severity of positive symptoms)
Time frame: Positive symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment.
Change in general symptom scores before and after intervention
Global Assessment of Functioning (GAF) score. The score ranges from 0 to 100 points. Higher scores indicate better levels of functioning.
Time frame: General symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment.
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Change in anxiety symptoms before and after intervention
Anxiety symptoms measured using Hamilton Anxiety Rating Scale (HAMA). Each item scored 0 (not present) to 4 (severe), total score range 0-56. Higher scores indicate more severe symptoms.
Time frame: Anxiety symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment.
Depressive symptoms changes
Depressive symptoms measured using Hamilton Depression Rating Scale (HAMD). Measure of depression severity - total score ranges from 0 (no depression) to 76 (most severe depression)
Time frame: Depressive symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment.
Safety as measured by number of participants with Adverse Events
Number of Adverse Events reported during TMS treatment
Time frame: Record the adverse events reported on that day after completing the day's TMS treatment. This should be done every day during the treatment period (Day 0 - Day 14)
Resting-state functional MRI (rsfMRI) scan
Functional MRI scan will be conducted before and after treatment to assess treatment-induced changes in brain connectivity
Time frame: Resting-state functional MRI will be measured at baseline (Day-4±2), and immediately after the 50th session of TMS (Day 14).