中藥與抗精神病藥物合併使用對失智症患者的錐體外症候群風險影響：回顧性研究

The extrapyramidal syndrome risk of traditional Chinese medicine and antipsychotics drugs combined usage in dementia patients: a retrospective study

錐體外症候群（Extrapyramidal syndrome, EPS）是抗精神病藥物已知的副作用，特別是在失智症患者中。過去研究已發現思覺失調症患者若長時間合併使用抗精神病藥物和中藥，可能加重錐體外症候群、出現遲發性運動障礙、增加意外跌倒的風險，甚至會引起急性的精神症狀發作。我們以過去藥物不良反應研究顯示較有可能發生副作用的中藥(柴胡、梔子、五味子、熟地和車前子)與抗精神病西藥(Flunarizine, Cinnarizine, Risperidone, Olanzapine, Quetiapine)合併使用作為研究標的。
本回顧性世代研究評估了在失智症患者中使用中藥與抗精神病藥物合併治療的錐體外症候群風險。共有74,558名接受抗精神病治療的患者被分為三組：未合併使用中藥的患者的患者（n = 59,188，佔79.4%）、合併使用其他中藥的患者（n = 11,826，佔15.9%）、合併使用高風險中藥的患者（n = 3,544，佔4.8%）。
在校正年齡、性別、保險金額、都市化水平和共病疾病後，相較於未使用中藥的患者，使用高風險中藥的患者的錐體外症候群風險比（HR）為1.12（95%信賴區間[CI]：0.93-1.31；p>0.05）。然而，使用高風險中藥超過60天的患者顯示出顯著更高的風險，其調整後風險比（aHR）為2.06（95% CI：1.60-2.52；p=0.01）。失智病程超過五年的患者，若合併使用高風險中藥與抗精神病藥物，展示出更高的錐體外症候群風險，其aHR為2.31（95% CI：1.87-3.41；p=0.01）。
研究結果顯示，在失智症患者中長期合併使用中藥與抗精神病藥物可能顯著增加發展錐體外症候群的風險。這些結果強調了在這一易感人群中合併使用中藥與抗精神病藥物時需謹慎的重要性。

Extrapyramidal syndrome (EPS) is a recognized adverse effect of antipsychotic drugs, particularly in dementia patients. There is emerging evidence suggesting that combining traditional Chinese medicine (TCM) with antipsychotic drugs may exacerbate this risk. We selected traditional TCMs that had been previously identified in adverse drug reaction studies as more likely to cause side effects—namely Bupleurum (Chai Hu), Gardenia (Zhi Zi), Schisandra (Wu Wei Zi), Rehmannia (Shu Di Huang), and Plantago (Che Qian Zi)—for combined use with antipsychotic medications (Flunarizine, Cinnarizine, Risperidone, Olanzapine, Quetiapine) as subjects for our study.
This retrospective cohort study evaluated the risk of EPS associated with the concurrent use of TCM and antipsychotic drugs in dementia patients. A total of 74,558 patients who received antipsychotic therapy were classified into three groups: those who used high-risk TCM (n = 3,544; 4.8%), those who used other TCMs (n = 11,826; 15.9%), and those who did not use TCM (n = 59,188; 79.4%).
After adjusting for age, gender, insured amount, urbanization level, and comorbid diseases, the hazard ratio (HR) for EPS was 1.12 (95% confidence interval (CI) 0.93-1.31; p > 0.05) in patients using high-risk TCM compared to those not using TCM. However, patients using high risk TCM for more than 60 days exhibited a significantly higher risk, with an aHR of 2.06 (95% CI: 1.60-2.52; p = 0.01). Patients with a dementia duration exceeding five years who concurrently used high-risk TCM and antipsychotic drugs exhibited an elevated risk of EPS, and the aHR was 2.31 (95% CI: 1.87-3.41; p = 0.01) .
The findings suggest that the long-term combination of TCM and antipsychotic drugs in dementia patients significantly could increases the risk of developing EPS. These results underline the importance of cautious use of TCM in conjunction with antipsychotic medications in this vulnerable population.