Efficacy of Repetitive Transcranial Magnetic Stimulation for Improving Depressive Symptoms in Patients With Parkinson's Disease

Efficacy of Repetitive Transcranial Magnetic Stimulation for Improving Depressive Symptoms in Patients With Parkinson's Disease : A Single-Center, Randomized, Single-Blinded, Sham-Controlled, Parallel-Design, Investigator-Initiated Exploratory Clinical Trial

The purpose of this study is to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving depressive symptoms in patients with Parkinson's Disease (PD).

Participants will be randomly assigned to either an active rTMS group or a sham-control group.

The study aims to establish an optimal treatment protocol using a neuronavigation system and to validate treatment responses through various digital biomarkers such as facial expression analysis and eye-tracking.

Inclusion Criteria:

• Willing and able to provide written informed consent
• Male or female aged 40 to 90 years
• Diagnosed with Parkinson's disease with depressive symptoms
• Hoehn and Yahr stage 1 to 3
• On stable Parkinson's disease medication for at least 3 months prior to screening, with no planned dose increase during the study period
• BDI-II score ≥ 14 (mild depression) or ≥ 20 (moderate depression)
• Able to read and write Korean and capable of independently completing questionnaires

Exclusion Criteria:

• History of epilepsy
• Parkinson's disease caused by cerebrovascular disease, CNS infection, intoxication, or traumatic brain injury
• Diagnosed with Parkinson-plus syndromes (multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies etc.)
• Clinically significant abnormal laboratory values (AST, ALT, or total bilirubin > 2.5 x ULN)
• Diagnosed with psychiatric disorders
• Unable to follow instructions or communicate
• Pregnant, breastfeeding, or women of childbearing potential
• Febrile patients
• Patients with artificial hip joint implants
• Presence of conductive, ferromagnetic, or magnetically sensitive metal near the head or treatment coil (e.g., cochlear implants, implanted electrodes/stimulators, aneurysm clips or coils)
• Cardiac disease, especially patients with pacemakers
• Corrected or uncorrected visual acuity less than 0.5
• Use of drug infusion pumps or hearing aids
• Patients with acute illness
• Patients taking tricyclic antidepressants, neuroleptics, or other medications that may lower seizure threshold
• History of increased intracranial pressure or head trauma
• Evidence of external wounds on brain or neck
• Prominent psychotic symptoms other than depression (high NPI scores for hallucinations, delusions, mania)
• History of schizophrenia, bipolar disorder, or substance abuse
• Suicidal ideation (BDI-II item 9 score of 2 or 3)
• History of or planned deep brain stimulation or stereotactic surgery (pallidotomy, thalamotomy)
• Any participant deemed ineligible by the investigator, including those with medical conditions that may increase risk or interfere with study evaluation
• Currently enrolled in another clinical trial or used investigational drug/device within 30 days or 5 half-lives prior to consent