Qiu Huaide, Liu Cheng, Wang Zhixiang
School of Rehabilitation Science, Nanjing Normal University of Special Education, Nanjing, China.
Department of Rehabilitation Medicine, Yixing No. 2 People's Hospital (Yixing Prevention and Treatment Hospital for Occupational Diseases), Yixing, Jiangsu, China.
Front Pharmacol. 2025 Mar 6;16:1529932. doi: 10.3389/fphar.2025.1529932. eCollection 2025.
Levodopa-induced motor complications are a significant concern in the treatment of Parkinson's disease (PD). Dopamine decarboxylase inhibitors (DCIs) such as benserazide (BSZ) and carbidopa (CD) are commonly used in conjunction with levodopa to manage PD symptoms. However, their association with motor complications remains unclear.
We performed a retrospective pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) data from Q1 2004 to Q2 2024. The study included only adverse event reports (AERs) related to oral administration of drugs indicated for PD. We concentrated on motor complications, selecting two system organ classes (SOCs) associated with motor fluctuations and dyskinesia: nervous system disorders and general disorders/administration site conditions. Disproportionality analysis and Bayesian methods were utilized to identify and assess motor complication signals associated with BSZ and CD. A signal was deemed significant if it met the following criteria: reporting odds ratio (ROR) ≥ 3 with a 95% confidence interval (CI) lower bound >1, information component (IC) 95% CI lower bound >0, and empirical Bayes geometric mean (EBGM) 95% CI lower bound >2.
The analysis identified 8,744 AERs related to motor complications, recording 19,482 adverse events (AEs). The study highlighted motor complications such as dyskinesia, the on-off phenomenon, freezing episodes, and wearing-off, linked to the oral use of both BSZ and CD. Dyskinesia showed high RORs for both BSZ (16.5, 95% CI 14.76-18.45) and CD (13.81, 95% CI 13.02-14.65). The on-off phenomenon demonstrated a more pronounced ROR for BSZ at 170.74 (95% CI 145.03-201.01) compared to CD at 67.5 (95% CI 59.46-76.63). Wearing-off was notably higher for CD, with an ROR of 7.66 (95% CI 7.08-8.28), compared to BSZ's ROR of 3.03 (95% CI 2.37-3.88).
The findings indicate that the choice of DCI affects the risk profile of motor complications in PD. BSZ is associated with increased risks of dyskinesia and the on-off phenomenon, whereas CD is linked to a higher risk of wearing-off. Future research should explore the mechanisms underlying these differences to guide the selection of the most appropriate DCI for individual patients.
左旋多巴诱发的运动并发症是帕金森病（PD）治疗中的一个重要问题。多巴胺脱羧酶抑制剂（DCI），如苄丝肼（BSZ）和卡比多巴（CD），通常与左旋多巴联合使用以控制PD症状。然而，它们与运动并发症之间的关联仍不明确。
我们使用2004年第一季度至2024年第二季度的美国食品药品监督管理局不良事件报告系统（FAERS）数据进行了一项回顾性药物警戒分析。该研究仅纳入与口服用于PD的药物相关的不良事件报告（AER）。我们专注于运动并发症，选择了与运动波动和异动症相关的两个系统器官类别（SOC）：神经系统疾病和全身疾病/给药部位情况。采用不成比例分析和贝叶斯方法来识别和评估与BSZ和CD相关的运动并发症信号。如果信号符合以下标准，则被认为具有显著性：报告比值比（ROR）≥3，95%置信区间（CI）下限>1，信息成分（IC）95%CI下限>0，以及经验贝叶斯几何均值（EBGM）95%CI下限>2。
分析确定了8744份与运动并发症相关的AER，记录了19482起不良事件（AE）。该研究突出了与口服BSZ和CD相关的运动并发症，如异动症、开关现象、冻结发作和剂末现象。异动症在BSZ（16.5，95%CI 14.76 - 18.45）和CD（13.81，95%CI 13.02 - 14.65）中均显示出高ROR。开关现象在BSZ中的ROR为170.74（95%CI 145.03 - 201.01），比CD的67.5（95%CI 59.46 - 76.63）更为显著。剂末现象在CD中更为明显，ROR为7.66（95%CI 7.08 - 8.28），而BSZ的ROR为3.03（95%CI 2.37 - 3.88）。
研究结果表明，DCI的选择会影响PD中运动并发症的风险状况。BSZ与异动症和开关现象风险增加相关，而CD与更高的剂末现象风险相关。未来的研究应探索这些差异背后的机制，以指导为个体患者选择最合适的DCI。
