Manchado Perero Sofía, Rodríguez Lorente Ana, García-Pérez Alba, Isidro García Guillermo, Forcen-Muñoz Luis Alberto, Ovejero García Santiago, Sáez Povedano Rocío, González-Galdámez Ana Luisa, Mata Iturralde Laura, Ramirez Bonilla Mariluz, Fuentes-Pérez Paloma, Ovejas-Catalán Claudia, Suárez-Pinilla Paula, Fernández Abascal Blanca, Omaña Colmenares Miguel, Campos-Navarro María Pilar, Baca-García Enrique, Lara Fernández Ana, Benavente-López Sergio, Raya Platero Alberto, Barberán Navalón Miguel, Sánchez-Alonso Sergio, Vázquez-Bourgon Javier, Pappa Sofia, García-Carmona Juan Antonio
Department of Psychiatry, Fundación Jiménez Díaz University Hospital, Madrid, Spain.
Department of Psychiatry, Santa Lucía University Hospital, Cartagena, Murcia, Spain.
Front Psychiatry. 2025 Mar 4;16:1540213. doi: 10.3389/fpsyt.2025.1540213. eCollection 2025.
LAIs with longer dosing intervals appear to be associated with improved clinical outcomes and added real-world benefits in the management of schizophrenia. Paliperidone palmitate six-monthly (PP6M) LAI provides the longest dosing interval, twice-yearly dosing, among all currently available LAIs. In clinical trials PP6M was found to be non-inferior in preventing relapses in patients with schizophrenia compared to the three monthly formulation (PP3M) though real world data remain limited. Therefore, the aim of this study was to evaluate the acceptability, effectiveness, and safety of PP6M in patients with schizophrenia in real world practice.
Data were derived from a naturalistic cohort of patients enrolled in the international, multicenter, prospective Paliperidone-2-per Year (P2Y) study. In this 2-year mirror-image study we compare the number of hospital admissions 1 year pre- and post-PP6M initiation as well as the CGI scores at baseline and the point of each PP6M administration. Discontinuation rates and reasons were also collected.
A total of 201 patients (107 outpatients and 94 chronic long-stay inpatients) were included. The majority of patients had switched to PP6M from either PP3M (76%) or PP1M (19%) while the 3% switched from aripiprazole 1-monthly and the 2% from risperidone-LAI and zuclopenthixol-LAI. The mean CGI-Severity score significantly reduced from baseline to the second and third PP6M administrations in the global cohort (2.31 ± 0.14 . 3.23, p=0.001) as well as in both subgroups. Moreover, the number of hospital admissions decreased from 0.2 ± 0.04 1-year period before to 0.07 ± 0.02 1 year after PP6M initiation (p=0.001). Only 6%, (12 patients, 10 out- and 2 inpatients) discontinued treatment at 1 year of follow-up; Kaplan-Meier curves demonstrated significant differences in PP6M treatment discontinuation between out- and inpatients (p=0.012). The main reason for discontinuation was lack of adherence (5 patients) while only 1 patient stopped treatment due to tolerability issues (extrapyramidal side effects).
This is the first mirror-image study in patients with schizophrenia treated with PP6M in real-world settings showing very high treatment persistence, reduced hospital admissions compared to previous LAIs and no major safety concerns. Our findings suggest that six-monthly treatment with a long-acting antipsychotic may confer additional benefits in the management of schizophrenia. Nonetheless, we were unable to determine the precise changes in symptoms. Therefore, future studies are needed to truly establish the role of PP6M.
给药间隔较长的长效注射剂（LAIs）似乎与改善精神分裂症管理的临床结局及增加现实世界中的益处相关。棕榈酸帕利哌酮半年注射剂（PP6M）是所有现有LAIs中给药间隔最长的，为每年注射两次。在临床试验中，发现PP6M在预防精神分裂症患者复发方面不劣于三个月剂型（PP3M），不过现实世界的数据仍然有限。因此，本研究的目的是评估PP6M在现实世界实践中对精神分裂症患者的可接受性、有效性和安全性。
数据来源于参与国际多中心前瞻性每年两次帕利哌酮（P2Y）研究的自然队列患者。在这项为期2年的镜像研究中，我们比较了PP6M开始使用前1年和开始使用后1年的住院次数，以及基线时和每次PP6M给药时的临床总体印象量表（CGI）评分。还收集了停药率及原因。
共纳入201例患者（107例门诊患者和94例慢性长期住院患者）。大多数患者从PP3M（76%）或PP1M（19%）换用了PP6M，而3%的患者从每月一次阿立哌唑换用，2%的患者从长效注射用利培酮和长效注射用珠氯噻醇换用。在总体队列中，从基线到第二次和第三次PP6M给药时，CGI严重程度评分显著降低（2.31±0.14对3.23，p=0.001），两个亚组均如此。此外，住院次数从PP6M开始使用前1年的0.2±0.04次降至开始使用后1年的0.07±0.02次（p=0.001）。在随访1年时，只有6%（12例患者，10例门诊患者和2例住院患者）停药；Kaplan-Meier曲线显示门诊患者和住院患者在PP6M治疗停药方面存在显著差异（p=0.012）。停药的主要原因是依从性差（5例患者），而只有1例患者因耐受性问题（锥体外系副作用）停止治疗。
这是第一项在现实世界环境中对接受PP6M治疗的精神分裂症患者进行的镜像研究，结果显示治疗依从性非常高，与之前的LAIs相比住院次数减少，且无重大安全问题。我们的研究结果表明，长效抗精神病药物半年一次的治疗可能在精神分裂症管理中带来额外益处。尽管如此，我们无法确定症状的确切变化。因此，需要未来的研究来真正确立PP6M的作用。
