rTMS for Depressive, Positive and Negative Symptoms, and Physiological Indices of Schizophrenia Patients

Therapeutic Effect of Repetitive Transcranial Magnetic Stimulation for Depressive, Positive and Negative Symptoms, and Physiological Indices of Schizophrenia Patients

Around 40% of schizophrenia patients present depressive symptoms, which are associated with elevated suicide and violence risk and poor prognosis and quality of life. Recent meta-analysis showed the effect size of antidepressants for depressive symptoms of schizophrenia patients was as low as 0.25, so new therapeutic approach is warranted.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive, anesthesia-free brain stimulation therapy for treatment refractory depression. Currently, rTMS is classified as high-frequency stimulation (>5Hz, usually 10Hz or 20Hz) and low-frequency inhibition (usually 1Hz). Intermittent theta burst stimulation (iTBS) is a new variant of rTMS, with stimulation frequency as high as 50Hz. Compared with high-frequency rTMS, iTBS has similar therapeutic effect and shorter stimulation duration. Up to now, studies exploring treatment effect of rTMS or iTBS for schizophrenia patients mainly focused on negative symptoms rather than depressive symptoms. Therefore, this study aims to explore treatment effect of rTMS or iTBS of depressive symptoms, negative symptoms, cognitive function and physiological indices for schizophrenia patients.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia and Related Disorders
• Intervention / Treatment: Device: Repetitive Transcranial Magnetic Stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chia-Hao Ma, MD; Phone Number: 7107 +886-5-5323911; Email: chiahaoma.tw@gmail.com

Study Locations

• Taiwan
  • Douliu, Yunlin, Taiwan, 640
    • Recruiting
    • Department of Psychiatry, National Taiwan University Hospital Yunlin Branch
    • Contact: Chia-Hao Ma, MD; Phone Number: 7107 +886-5-532-3911; Email: chiahaoma.tw@gmail.com
    • Principal Investigator: Chia-Hao Ma, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 20 years
• Able to give informed consent
• Diagnosed with schizophrenia or schizoaffective disorder according to DSM-5
• Has a score ≥ 7 on Calgary depression scale for schizophrenia
• The principal psychotropic agents are not changed within one month of the first session of rTMS

Exclusion Criteria:

• DSM-5 defined substance use disorder (excluding tobacco) in the past 3 months
• Have clinically relevant cognitive impairment (e.g., delirium, intellectual disability or MMSE < 15)
• With electronic and/or magnetic implants (e.g. pacemaker, implantable cardioverter defibrillator [ICD], cerebral shunts, cochlear implant, etc.)
• With metallic or mechanic fragments (e.g., screws, plates, stents, clips, etc.)
• Pregnant, or has a pregnancy plan within 3 months
• With any known or history of neurological conditions including cerebral vascular accidents, epilepsy (or epileptiform waves detected by EEG prior to the first session of rTMS), brain tumor or space occupying lesion
• Received rTMS or iTBS treatment within 3 months
• Has a clinically significant abnormality on the screening examination that might affect safety, study participation, or confound interpretation of study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: conventional rTMS; target: left DLPFC protocol: 10Hz for 4 seconds, 120% motor threshold, 75 trains with 26-second interval, 3000 pulses per session, one session per day, five sessions per week, two weeks in total	Device: Repetitive Transcranial Magnetic Stimulation; rTMS using Magstim TMS system is delivered at the left dorsolateral prefrontal cortex
Experimental: iTBS; target: left DLPFC protocol: 3 pulses at 50Hz, 90% motor threshold, repeated at 5Hz, 60 trains of 10 bursts with 8-second intervals, 1800 pulses per session, one session per day, five sessions per week, two weeks in total	Device: Repetitive Transcranial Magnetic Stimulation; rTMS using Magstim TMS system is delivered at the left dorsolateral prefrontal cortex
Sham Comparator: sham rTMS; target: left DLPFC sham probe, the same protocol as active conventional rTMS	Device: Repetitive Transcranial Magnetic Stimulation; rTMS using Magstim TMS system is delivered at the left dorsolateral prefrontal cortex
Sham Comparator: sham iTBS; target: left DLPFC sham probe, the same protocol as active iTBS	Device: Repetitive Transcranial Magnetic Stimulation; rTMS using Magstim TMS system is delivered at the left dorsolateral prefrontal cortex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Calgary Depression Scale for Schizophrenia	A 9-item scale developed for detecting major depressive episode for schizophrenia patients. Total score ranges from 0 to 27. Lower score indicates less depressive symptoms. A cut-off of 7 points yields to sensitivity of 85% and specificity of 82%.	baseline (Day 1), Day 8, Day 15, Day 29, Day 57, Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Positive and Negative syndrome scale	A 30-item scale developed to evaluating positive, negative and general symptoms for schizophrenia patients. Total score ranges from 30 to 210. Lower score indicates fewer schizophrenic symptoms.	baseline (Day 1), Day 8, Day 15, Day 29, Day 57, Day 85
Change from Baseline in Negative symptoms assessment 16	A scale developed to evaluating negative symptoms for schizophrenia patients. Items are scored based on behaviors during the interview (items 1-4, 6, 7, 9, 11, 15, 16) or previous 7 days (items 5, 8, 10, 12-14) on a 6-point scale from 1 to 6. The NSA-16 domain scores are the sum of item scores in each domain i.e. communication (min score 4, max score 24), emotion/affect (min 3, max 18), social involvement (min 3, max 18), motivation (min 4, max 24), and retardation (min 2, max 12); with higher scores denoting more severe negative symptoms in schizophrenia.	baseline (Day 1), Day 8, Day 15, Day 29, Day 57, Day 85
Change from Baseline in Clinical global impression	A scale for primary-care psychiatrist to evaluate global symptom severity of a patient in comparison with others with same diagnosis. Lower score indicates less severe illness.	baseline (Day 1), Day 8, Day 15, Day 29, Day 57, Day 85
Change from Baseline in Self-Reported Graphic version of the Personal and Social Performance Scale	A 22-item self-rated scale for schizophrenia patients, which includes four domains, i.e., global function (6 items, total scores 6-18), personal and social performance (5 items, total scores 5-15), self-care (6 items, total scores 6-18) and disturbing behaviors (5 items, total scores 5-15). Lower score indicates less severe illness.	baseline (Day 1), Day 8, Day 15, Day 29, Day 57, Day 85

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Physiological Parameters - Heart Rate Variability	Measurement of parasympathetic activity.	baseline (Day 1), Day 8, Day 15, Day 29, Day 57, Day 85
Change from Baseline in Physiological Parameters - Skin Conductance	Measurement of sympathetic activity.	baseline (Day 1), Day 8, Day 15, Day 29, Day 57, Day 85
Change from Baseline in Physiological Parameters - Body Temperature	Measurement of autonomic nervous system.	baseline (Day 1), Day 8, Day 15, Day 29, Day 57, Day 85
Change from Baseline in Physiological Parameters - Respiratory Rate	Measurement of autonomic nervous system.	baseline (Day 1), Day 8, Day 15, Day 29, Day 57, Day 85

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Chia-Hao Ma, MD, Department of Psychiatry, National Taiwan University Hospital Yunlin Branch

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: December 18, 2022
• First Submitted That Met QC Criteria: January 2, 2023
• First Posted (Actual): January 4, 2023

Study Record Updates

• Last Update Posted (Actual): January 4, 2023
• Last Update Submitted That Met QC Criteria: January 2, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Schizophrenia; repetitive transcranial magnetic stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 202210011DINC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No