Schizophrenia and bipolar disorder are severe mental illnesses which are highly prevalent worldwide. Risperidone and Paliperidone are treatments for either illnesses, but their efficacy compared to other antipsychotics and growing reports of hormonal imbalances continue to raise concerns. As existing evidence on both antipsychotics are solely based on aggregate data, we aimed to assess the benefits and harms of Risperidone and Paliperidone in the treatment of patients with schizophrenia or bipolar disorder, using individual participant data (IPD), clinical study reports (CSRs) and publicly available sources (journal publications and trial registries). We searched MEDLINE, Central, EMBASE and PsycINFO until December 2020 for randomised placebo-controlled trials of Risperidone, Paliperidone or Paliperidone palmitate in patients with schizophrenia or bipolar disorder. We obtained IPD and CSRs from the Yale University Open Data Access project. The primary outcome Positive and Negative Syndrome Scale (PANSS) score was analysed using one-stage IPD meta-analysis. Random-effect meta-analysis of harm outcomes involved methods for coping with rare events. Effect-sizes were compared across all available data sources using the ratio of means or relative risk. We registered our review on PROSPERO, CRD42019140556. Of the 35 studies, IPD meta-analysis involving 22 (63%) studies showed a significant clinical reduction in the PANSS in patients receiving Risperidone (mean difference − 5.83, 95% CI − 10.79 to − 0.87, I2 = 8.5%, n = 4 studies, 1131 participants), Paliperidone (− 6.01, 95% CI − 8.7 to − 3.32, I2 = 4.3%, n = 13, 3821) and Paliperidone palmitate (− 7.89, 95% CI − 12.1 to − 3.69, I2 = 2.9%, n = 5, 2209). CSRs reported nearly two times more adverse events (4434 vs. 2296 publication, relative difference (RD) = 1.93, 95% CI 1.86 to 2.00) and almost 8 times more serious adverse events (650 vs. 82; RD = 7.93, 95% CI 6.32 to 9.95) than the journal publications. Meta-analyses of individual harms from CSRs revealed a significant increased risk among several outcomes including extrapyramidal disorder, tardive dyskinesia and increased weight. But the ratio of relative risk between the different data sources was not significant. Three treatment-related gynecomastia events occurred, and these were considered mild to moderate in severity. IPD meta-analysis conclude that Risperidone and Paliperidone antipsychotics had a small beneficial effect on reducing PANSS score over 9 weeks, which is more conservative than estimates from reviews based on journal publications. CSRs also contained significantly more data on harms that were unavailable in journal publications or trial registries. Sharing of IPD and CSRs are necessary when performing meta-analysis on the efficacy and safety of antipsychotics.

中文翻译：

---

利培酮和帕潘立酮治疗精神分裂症或双相情感障碍患者的利与弊：一项涉及个体参与者数据和临床研究报告的荟萃分析

精神分裂症和双相情感障碍是严重的精神疾病，在世界范围内非常普遍。利培酮和帕潘立酮可治疗这两种疾病，但与其他抗精神病药相比，它们的疗效以及越来越多的荷尔蒙失衡报告继续引起人们的关注。由于关于这两种抗精神病药的现有证据完全基于汇总数据，我们旨在使用个体参与者数据 (IPD)、临床研究报告 (CSR) 评估利培酮和帕潘立酮在治疗精神分裂症或双相情感障碍患者中的​​益处和危害和公开来源（期刊出版物和试验注册）。我们在 MEDLINE、Central、EMBASE 和 PsycINFO 中检索了截至 2020 年 12 月的利培酮随机安慰剂对照试验，精神分裂症或双相情感障碍患者的帕潘立酮或帕潘立酮棕榈酸酯。我们从耶鲁大学开放数据访问项目中获得了 IPD 和 CSR。使用一阶段 IPD 荟萃分析分析主要结果阳性和阴性综合征量表 (PANSS) 评分。伤害结果的随机效应荟萃分析涉及应对罕见事件的方法。使用均值或相对风险的比率在所有可用数据源中比较了效果大小。我们在 PROSPERO 上注册了我们的评论，CRD42019140556。在 35 项研究中，涉及 22 项（63%）研究的 IPD 荟萃分析显示，接受利培酮治疗的患者的 PANSS 临床显着降低（平均差 - 5.83，95% CI - 10.79 至 - 0.87，I2 = 8.5%，n = 4 项研究，1131 名参与者），帕利哌酮（- 6.01，95% CI - 8.7 至 - 3.32，I2 = 4.3%，n = 13，3821) 和帕潘立酮棕榈酸酯 (− 7.89, 95% CI − 12.1 至 − 3.69, I2 = 2.9%, n = 5, 2209)。CSR 报告的不良事件几乎是 2 倍（4434 与 2296 次发表，相对差异 (RD) = 1.93，95% CI 1.86 至 2.00）和几乎 8 倍的严重不良事件（650 与 82；RD = 7.93，95% CI 6.32 到 9.95) 比期刊出版物。CSR 对个体危害的荟萃分析显示，锥体外系障碍、迟发性运动障碍和体重增加等多种结局的风险显着增加。但不同数据源之间的相对风险比不显着。发生了三起与治疗相关的男性乳房发育事件，这些事件的严重程度被认为是轻度至中度。IPD 荟萃分析得出结论，利培酮和帕潘立酮抗精神病药在 9 周内对降低 PANSS 评分有很小的有益作用，这比基于期刊出版物的评论估计更保守。CSR 还包含更多关于期刊出版物或试验注册处无法获得的危害数据。在对抗精神病药的有效性和安全性进行荟萃分析时，IPD 和 CSR 的共享是必要的。