Effectiveness and safety of theta burst stimulation for Parkinson's disease: an updated systematic review and meta-analysis of randomized parallel-group controlled trials

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor impairments that are often incompletely controlled by pharmacological treatment. Theta burst stimulation (TBS), including transcranial and transspinal approaches, has emerged as a potential neuromodulation strategy for symptom management in PD. This updated systematic review and meta-analysis evaluated the efficacy and safety of TBS for motor and non-motor outcomes in individuals with PD.

PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched from inception to 28 July 2026. Randomized parallel-group controlled trials comparing active TBS with sham stimulation in individuals with PD were included. Two reviewers independently performed study selection, data extraction, and risk of bias assessment using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses were conducted, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.

Twelve randomized parallel-group controlled trials including 388 participants were included. Active transcranial TBS significantly improved motor symptoms in the OFF-medication state (SMD = -0.43; 95% CI, -0.78 to -0.09; P = 0.01; I ² = 3%; high-certainty evidence), whereas no significant benefit was observed in the ON-medication state or at 1-month follow-up. Active transcranial TBS also reduced depressive symptom scores (SMD = -0.60; 95% CI, -1.07 to -0.12; P = 0.01; I ² = 36%; high-certainty evidence). Moderate-certainty evidence indicated potential improvements in cognitive outcomes following transcranial TBS immediately after treatment and at 3-month follow-up, as well as potential motor benefits of transspinal TBS immediately after treatment in the ON-medication state. These findings should be interpreted cautiously given the small number of trials and participants and heterogeneity in anatomical stimulation targets and stimulation protocols. No serious stimulation-related adverse events were reported.

Transcranial TBS may improve short-term motor symptoms in the OFF-medication state and reduce depressive symptom scores. Cognitive benefits following transcranial TBS and the potential motor effects of transspinal TBS warrant cautious interpretation. Larger trials with standardized stimulation protocols and longer follow-up are needed to establish the durability and clinical relevance of these effects.

https://www.crd.york.ac.uk/prospero/search, identifier CRD420261285544.