Division of Epidemiology 1 (Mosholder, Leishear), Division of Neurology 1 (Podskalny), Office of Pharmacovigilance and Epidemiology (Graham), and Division of Biometrics 7 (Ma), U.S. Food and Drug Administration Center for Drug Evaluation and Research, Silver Spring, Md.; Acumen LLC, Burlingame, Calif. (Akhtar, Feng, Lyu, Liao, Wei, Wernecke, Nelson, MaCurdy); Guardant Health, Redwood City, Calif. (Liao); Department of Epidemiology and Population Health (Nelson) and Department of Economics (MaCurdy), Stanford University, Stanford, Calif.; Centers for Medicare and Medicaid Services, Washington, DC (Kelman).
Am J Psychiatry. 2022 Aug;179(8):553-561. doi: 10.1176/appi.ajp.21090876. Epub 2022 Jun 15.
Pimavanserin, a serotonin 5-HT 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.
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).
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.
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.
匹莫范色林是一种 5-羟色胺 5-HT 拮抗剂，用于治疗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莫范色林治疗期间死亡。抗精神病药在帕金森病精神病中被超适应证使用，会增加痴呆患者的死亡率。作者在一个大型数据库中比较了匹莫范色林和非典型抗精神病药的死亡率。
这是一项回顾性新用户队列研究，纳入了 2016 年 4 月至 2019 年 3 月期间开始使用匹莫范色林（N=3227）或非典型抗精神病药（N=18442）的 Medicare 受益人的数据。使用分段比例风险回归估计匹莫范色林与非典型抗精神病药相比的全因死亡率风险比和 95%置信区间，治疗时间为 1-180 天和 181 天以上。通过逆概率治疗加权（IPTW）来解决潜在的混杂因素。
匹莫范色林使用者的平均年龄约为 78 岁，45%为女性。在 IPTW 之前，一些合并症在非典型抗精神病药使用者中更为常见；在 IPTW 之后，两组之间的合并症平衡良好。在治疗的前 180 天，匹莫范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 例接受非典型抗精神病药治疗的患者中就有 1 例额外死亡；然而，在 180 天以上的治疗期间，匹莫范色林没有额外的死亡优势（风险比=1.05，95%CI=0.82，1.33）。匹莫范色林在疗养院患者中没有显示出死亡率优势。
在治疗的前 180 天内，匹莫范色林的使用与非典型抗精神病药的使用相比，死亡率较低，但仅限于社区居住的患者，而不适用于疗养院居民。
