Objective:

Pimavanserin, a serotonin 5-HT₂ antagonist, is indicated for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. In premarketing trials in patients with Parkinson’s disease psychosis, 11% of patients died during open-label pimavanserin treatment. Antipsychotics, which are used off-label in Parkinson’s disease psychosis, increase mortality in dementia patients. The authors compared mortality with pimavanserin and atypical antipsychotics in a large database.

Methods:

This was a retrospective new-user cohort study of Medicare beneficiaries with Parkinson’s disease initiating pimavanserin (N=3,227) or atypical antipsychotics (N=18,442) from April 2016 to March 2019. All-cause mortality hazard ratios and 95% confidence intervals were estimated for pimavanserin compared with atypical antipsychotics, using segmented proportional hazards regression over 1–180 and 181+ days of treatment. Potential confounding was addressed through inverse probability of treatment weighting (IPTW).

Results:

Pimavanserin users had a mean age of approximately 78 years, and 45% were female. Before IPTW, some comorbidities were more prevalent in atypical antipsychotic users; after IPTW, comorbidities were well balanced between groups. In the first 180 days of treatment, mortality was approximately 35% lower with pimavanserin than with atypical antipsychotics (hazard ratio=0.65, 95% CI=0.53, 0.79), with approximately one excess death per 30 atypical antipsychotic–treated patients; however, during treatment beyond 180 days, there was no additional mortality advantage with pimavanserin (hazard ratio=1.05, 95% CI=0.82, 1.33). Pimavanserin showed no mortality advantage in nursing home patients.

Conclusions:

Pimavanserin use was associated with lower mortality than atypical antipsychotic use during the first 180 days of treatment, but only in community-dwelling patients, not nursing home residents.

中文翻译：

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帕金森病患者接受匹马万色林或非典型抗精神病药治疗的死亡率：医疗保险受益人的观察性研究

客观的：

Pimavanserin 是一种 5-羟色胺 5-HT ₂拮抗剂，适用于治疗与帕金森病精神病相关的幻觉和妄想。在帕金森病精神病患者的上市前试验中，11% 的患者在开放标签匹马万色林治疗期间死亡。抗精神病药在帕金森病精神病中的标签外使用会增加痴呆症患者的死亡率。作者在一个大型数据库中比较了匹马万色林和非典型抗精神病药的死亡率。

方法：

这是一项回顾性新用户队列研究，研究对象为 2016 年 4 月至 2019 年 3 月期间患有帕金森病并开始使用匹马万色林 (N=3,227) 或非典型抗精神病药物 (N=18,442) 的医疗保险受益人。估计了全因死亡率风险比和 95% 置信区间对于匹马万色林与非典型抗精神病药相比，在 1-180 天和 181 天以上的治疗中使用分段比例风险回归。通过治疗加权的逆概率 (IPTW) 解决了潜在的混杂问题。

结果：

Pimavanserin 使用者的平均年龄约为 78 岁，其中 45% 为女性。在 IPTW 之前，一些合并症在非典型抗精神病药物使用者中更为普遍；在 IPTW 之后，各组之间的合并症得到了很好的平衡。在治疗的前 180 天，匹马万色林的死亡率比非典型抗精神病药低约 35%（风险比 = 0.65, 95% CI = 0.53, 0.79），每 30 名非典型抗精神病药治疗的患者中约有 1 人死亡；然而，在超过 180 天的治疗期间，匹马万色林没有额外的死亡率优势（风险比=1.05, 95% CI=0.82, 1.33）。Pimavanserin 在疗养院患者中没有显示出死亡率优势。

结论：

在治疗的前 180 天内，使用匹马万色林的死亡率低于使用非典型抗精神病药物，但仅限于社区居民患者，而不是疗养院居民。