Objective To compare the efficacy of subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) on reducing levodopa‐induced dyskinesia (LID) in Parkinson’s disease, and to explore the potential underlying mechanisms. Methods We retrospectively assessed clinical outcomes in 43 patients with preoperative LID who underwent DBS targeting the STN (20/43) or GPi (23/43). The primary clinical outcome was the change from baseline in the Unified Dyskinesia Rating Scale (UDysRS) and secondary outcomes included changes in the total daily levodopa equivalent dose, the drug‐off Unified Parkinson Disease Rating Scale Part Ⅲ at the last follow‐up (median, 18?months), adverse effects, and programming settings. Correlation analysis was used to find potential associated factors that could be used to predict the efficacy of DBS for dyskinesia management. Results Compared to baseline, both the STN group and the GPi group showed significant improvement in LID with 60.73?±?40.29% (mean?±?standard deviation) and 93.78?±?14.15% improvement, respectively, according to the UDysRS score. Furthermore, GPi‐DBS provided greater clinical benefit in the improvement of dyskinesia (P??0.05) compared to the STN. Compared to the GPi group, the levodopa equivalent dose reduction was greater in the STN group at the last follow‐up (43.81% vs. 13.29%, P??0.05). For the correlation analysis, the improvement in the UDysRS outcomes were significantly associated with a reduction in levodopa equivalent dose in the STN group (r?=?0.543, P?=?0.013), but not in the GPi group (r?=??0.056, P?=?0.801). Interpretation Both STN and GPi‐DBS have a beneficial effect on LID but GPi‐DBS provided greater anti‐dyskinetic effects. Dyskinesia suppression for STN‐DBS may depend on the reduction of levodopa equivalent dose. Unlike the STN, GPi‐DBS might exert a direct and independent anti‐dyskinesia effect.
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