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：

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利培酮和帕潘立酮治疗精神分裂症或躁郁症患者的益处和危害：涉及个体参与者数据和临床研究报告的荟萃分析


精神分裂症和躁郁症是世界范围内非常流行的严重精神疾病。利培酮和帕潘立酮可以治疗这两种疾病，但与其他抗精神病药物相比，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担忧。由于这两种抗精神病药物的现有证据仅基于汇总数据，因此我们旨在利用个体参与者数据（IPD）、临床研究报告（CSR）来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​​益处和危害以及公开来源（期刊出版物和试验登记处）。我们检索了截至 2020 年 12 月的 MEDLINE、Central、EMBASE 和 PsycINFO，以查找利培酮、帕潘立酮或帕潘立酮棕榈酸酯治疗精神分裂症或双相情感障碍患者的随机安慰剂对照试验。我们从耶鲁大学开放数据访问项目获得了 IPD 和 CSR。使用一阶段 IPD 荟萃分析对主要结果阳性和阴性综合征量表 (PANSS) 评分进行分析。对伤害结果的随机效应荟萃分析涉及应对罕见事件的方法。使用均值比或相对风险对所有可用数据源的效应大小进行比较。我们在 PROSPERO 上注册了评论，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 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 名受试者）、帕潘立酮（− 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 报告的不良事件数量几乎是 2 倍（4434 例 vs. 2296 出版物，相对差异 (RD) = 1.93，95% CI 1.86 至 2.00），严重不良事件几乎是期刊出版物的 8 倍（650 比 82；RD = 7.93，95% CI 6.32 至 9.95）。对企业社会责任造成的个人危害的荟萃分析显示，多种结果的风险显着增加，包括锥体外系疾病、迟发性运动障碍和体重增加。但不同数据源之间的相对风险比并不显着。发生了三起与治疗相关的男性乳房发育症事件，这些事件的严重程度被认为是轻度至中度。 IPD 荟萃分析得出的结论是，利培酮和帕潘立酮抗精神病药在 9 周内对降低 PANSS 评分具有较小的有益作用，这比基于期刊出版物的评论的估计更为保守。 CSR 还包含更多有关期刊出版物或试验注册中无法获得的危害数据。在对抗精神病药物的有效性和安全性进行荟萃分析时，共享 IPD 和 CSR 是必要的。