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TOPLINE:

Daily 3-minute treatments with intermittent theta-burst stimulation (iTBS) for 2 weeks were associated with a greater reduction in depressive symptoms than sham stimulation in patients with Parkinson’s disease (PD), with efficacy comparable to daily 20-minute treatments with high-frequency repetitive transcranial magnetic stimulation (HF-rTMS), a new trial showed.

METHODOLOGY:

• Researchers conducted a triple-arm, randomized, sham-controlled clinical trial in China from 2024 to 2025, enrolling 54 patients with PD (mean age, 70 years; 54% men) and mild depressive symptoms (24-item Hamilton Depression Rating Scale [HAMD-24] total score, 8-20).
• Participants were randomly assigned (1:1:1) to receive either daily sessions of active iTBS (3 minutes 20 seconds), active HF-rTMS (20 minutes 4 seconds), or sham iTBS over 2 weeks.
• The primary outcome was a change in depressive symptoms at week 2, assessed via the HAMD-24 score. Secondary outcomes were changes in anxiety symptoms, motor symptoms, quality of life, and prefrontal hemodynamics measured using the 14-item Hamilton Anxiety Rating Scale (HAMA-14); Movement Disorder Society-Unified PD Rating Scale, Part III; 8-item PD Questionnaire (PDQ-8); and functional near-infrared spectroscopy (fNIRS), respectively.
• Assessments were conducted at baseline and weeks 1, 2, and 6. fNIRS was conducted at baseline and week 2. A total of 50 patients completed the trial.

TAKEAWAY:

• Compared with sham, both active interventions were associated with a greater reduction in depressive symptoms at week 1 (mean difference in HAMD-24 scores for both iTBS and HF-rTMS, -2.19), week 2 (iTBS, -4.97; HF-rTMS, -5.73), and week 6 (iTBS, -6.05; HF-rTMS, -5.57). No significant difference was observed between the active interventions at any timepoint.
• Compared with sham, iTBS was associated with significantly reduced anxiety symptoms at week 2 (mean difference in HAMA-14 scores, -4.04) and week 6 (-4.80), whereas HF-rTMS vs sham showed nonsignificant differences.
• Both active interventions were associated with improved quality of life compared with sham at week 2 (mean difference in PDQ-8 scores: iTBS, -2.33; HF-rTMS, -2.43) and week 6 (iTBS, -2.23; HF-rTMS, -2.63) No significant differences were observed between the active groups at any timepoint.
• Both iTBS and HF-rTMS were associated with increased activation of the left dorsolateral prefrontal cortex (estimated adjusted difference, iTBS, 151.18; HF-rTMS, 173.26) and reduced time in low-efficiency connectivity states (median change, iTBS, -0.12; HF-rTMS, -0.12) compared with sham.

IN PRACTICE:

“[T]he ultra-brief iTBS protocol achieved antidepressant efficacy comparable with that of standard HF-rTMS while markedly reducing treatment time, supporting its use as a pragmatic therapy for PD-D [PD depression],” the investigators wrote.

“This study suggests the promise of symptom-stratified neuromodulation for personalized treatment protocols,” they added.

SOURCE:

The study was led by Miaomiao Hou, MD, and Yu Zhang, PhD, Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, and Bingjie Tian, PhD, Huashan Hospital Fudan University, both in Shanghai, China. It was published online on May 20 in JAMA Network Open.

LIMITATIONS:

The single-center design and small sample size limited the generalizability of the findings. The 5-cm targeting rule introduced anatomical variability. The intensive treatment schedule may have hindered adherence among patients with impaired mobility. The unblinded treating clinician may have introduced a bias. Additionally, the study did not control for concurrent medications that could affect depressive symptoms. The dynamic fNIRS analysis was preliminary, and the cognitive verbal fluency task may have been suboptimal for probing emotion-related prefrontal dysfunction. Lastly, the lack of longitudinal assessments prevented drawing inferences about durability and causal direction between network reorganization and symptom improvement.

DISCLOSURES:

The study was funded by the Projects of National Science Foundation of China, Clinical Collaboration Project of Integrated Traditional Chinese and Western Medicine for Major and Refractory Diseases, Flagship Department of Collaborative Traditional Chinese and Western Medicine, Innovative Research Team of High-Level Local Universities in Shanghai, Medical Engineering Cross Research Fund of Shanghai Jiao Tong University, Medical Engineering Cross Research Fund of University of Shanghai for Science and Technology, and the Science and Technology Innovation Plan of the Shanghai Science and Technology Commission. The investigators reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.