Abstract：
BACKGROUND: Parkinson\'s disease (PD) patients are frequently exposed to antidepressant medications (ADMs). Norepinephrine (NE) and serotonin (5HT) systems have a role in levodopa-induced dyskinesias (LID) pathophysiology.
METHODS: We performed a longitudinal analysis on the PPMI cohort including drug-naïve PD patients, who are progressively exposed to dopamine replacement therapies (DRTs) to test the effect of ADM exposure on LID development by the 4th year of follow-up.
RESULTS: LID prevalence (according to MDS UPDRS score 4.1 ≥ 1) was 16% (42/251); these patients were more likely women (p = 0.01), had higher motor (p < 0.001) and depression scores (p = 0.01) and lower putaminal DAT binding ratio (p = 0.01). LID were associated with the exposure time to L-DOPA (2.2 ± 1.07 vs 2.6 ± 0.9, p = 0.02) and to the exposure to ADMs, in particular to SNRI (4.8% vs 21.4%, p < 0.001). The latter persisted after correcting for significant covariates (e.g., disease duration, cognitive status, motor impairment, depression, dopaminergic denervation). A similar difference in LID prevalence in PD patients exposed vs non-exposed to SNRI was observed on matched data by the real-world TriNetX repository (22% vs 13%, p < 0.001).
CONCLUSIONS: This study supports the presence of an effect of SNRI on LID priming in patients with early PD. Independent prospective cohort studies are warranted to further verify such association.
METHODS: We performed a longitudinal analysis on the PPMI cohort including drug-naïve PD patients, who are progressively exposed to dopamine replacement therapies (DRTs) to test the effect of ADM exposure on LID development by the 4th year of follow-up.
RESULTS: LID prevalence (according to MDS UPDRS score 4.1 ≥ 1) was 16% (42/251); these patients were more likely women (p = 0.01), had higher motor (p < 0.001) and depression scores (p = 0.01) and lower putaminal DAT binding ratio (p = 0.01). LID were associated with the exposure time to L-DOPA (2.2 ± 1.07 vs 2.6 ± 0.9, p = 0.02) and to the exposure to ADMs, in particular to SNRI (4.8% vs 21.4%, p < 0.001). The latter persisted after correcting for significant covariates (e.g., disease duration, cognitive status, motor impairment, depression, dopaminergic denervation). A similar difference in LID prevalence in PD patients exposed vs non-exposed to SNRI was observed on matched data by the real-world TriNetX repository (22% vs 13%, p < 0.001).
CONCLUSIONS: This study supports the presence of an effect of SNRI on LID priming in patients with early PD. Independent prospective cohort studies are warranted to further verify such association.
摘要：
背景：帕金森病（PD）患者经常接触抗抑郁药（ADM）。去甲肾上腺素（NE）和5-羟色胺（5HT）系统在左旋多巴诱导的运动障碍（LID）病理生理学中起作用。
方法：我们对PPMI队列进行了纵向分析，包括未服用药物的PD患者，他们逐渐暴露于多巴胺替代疗法（DRTs），以测试ADM暴露对LID发育的影响。
结果：LID患病率（根据MDSUPDRS评分4.1≥1）为16％（42/251）；这些患者更可能是女性（p=0.01），具有较高的运动（p<0.001）和抑郁评分（p=0.01）和较低的putaminalDAT结合率（p=0.01）。LID与L-DOPA的暴露时间（2.2±1.07vs2.6±0.9，p=0.02）和ADM的暴露时间相关，特别是SNRI(4.8%对21.4%，p<0.001)。后者在校正了显著的协变量后仍然存在(例如，疾病持续时间,认知状态，运动障碍,抑郁症,多巴胺能神经支配)。在现实世界TriNetX存储库的匹配数据上观察到暴露于SNRI的PD患者中LID患病率的相似差异（22％vs13％，p<0.001)。
结论：本研究支持SNRI对早期PD患者LID引发的影响。有必要进行独立的前瞻性队列研究以进一步验证这种关联。
方法：我们对PPMI队列进行了纵向分析，包括未服用药物的PD患者，他们逐渐暴露于多巴胺替代疗法（DRTs），以测试ADM暴露对LID发育的影响。
结果：LID患病率（根据MDSUPDRS评分4.1≥1）为16％（42/251）；这些患者更可能是女性（p=0.01），具有较高的运动（p<0.001）和抑郁评分（p=0.01）和较低的putaminalDAT结合率（p=0.01）。LID与L-DOPA的暴露时间（2.2±1.07vs2.6±0.9，p=0.02）和ADM的暴露时间相关，特别是SNRI(4.8%对21.4%，p<0.001)。后者在校正了显著的协变量后仍然存在(例如，疾病持续时间,认知状态，运动障碍,抑郁症,多巴胺能神经支配)。在现实世界TriNetX存储库的匹配数据上观察到暴露于SNRI的PD患者中LID患病率的相似差异（22％vs13％，p<0.001)。
结论：本研究支持SNRI对早期PD患者LID引发的影响。有必要进行独立的前瞻性队列研究以进一步验证这种关联。
