Taipale Heidi, Tanskanen Antti, Howes Oliver, Correll Christoph U, Kane John M, Tiihonen Jari
Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden; Center for Psychiatry Research, Stockholm City Council, Stockholm, Sweden; School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden; Center for Psychiatry Research, Stockholm City Council, Stockholm, Sweden; Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.
Lancet Psychiatry. 2025 Feb;12(2):122-130. doi: 10.1016/S2215-0366(24)00366-3.
The best pharmacological treatment practices for relapse prevention in patients with first-episode schizophrenia are unclear. We aimed to assess different treatment strategies used before and after the first relapse, and their associations with subsequent relapse risk.
In this population-based cohort study, we enrolled individuals (aged ≤45 years) with first-episode schizophrenia who were hospitalised and subsequently relapsed between 1996 and 2014 from the nationwide Finnish Hospital Discharge Register. Individuals who had not been taking antipsychotics within the year preceeding initial hospitalisation and who had a relapse within 5 years of discharge were included in the analyses. Treatment strategies were assessed during the 30 days before hospitalisation for the first relapse and 30 days after discharge and were categorised as either long-acting injectable, clozapine, non-clozapine oral antipsychotic monotherapy, non-clozapine oral antipsychotic polypharmacy, and antipsychotic non-use. Adjusted hazard ratios (aHRs) of the risk of second relapse based on treatment type were analysed with Cox regression models for 2 years after the first relapse, or until death or end of data linkage (Dec 31, 2017). People with lived experience of schizophrenia were not involved in the research and writing process.
Between Jan 31, 1996 and Dec 31, 2017, 3000 individuals had their first psychosis relapse and were eligible for analysis. Mean age was 30·0 years (SD 7·6), 1069 (35·6%) of patients were women and 1931 (64·4%) men. No ethnicity data were available. 2148 (71·7%) had a second relapse within 2 years. Before first relapse, most individuals were either not using antipsychotics (n=1366 [45·5%]), or were using non-clozapine oral antipsychotic monotherapy (n=973 [32·4%]). Compared with continuing the same treatment strategy used before the first relapse, switching to clozapine was associated with the lowest risk of second relapse compared with continuing any non-clozapine oral antipsychotic monotherapy (aHR 0·66, 95% CI 0·49-0·89; relapse rate 73·2% with oral non-clozapine antipsychotic monotherapy continuation vs 57·1% with switch to clozapine). Switching to another non-clozapine oral antipsychotic monotherapy (0·99, 0·76-1·28) was approximately as unhelpful in preventing the next relapse as switching to antipsychotic non-use (1·07, 0·80-1·42).
In patients with first-episode schizophrenia having their first psychosis relapse despite use of non-clozapine oral antipsychotics, continuation with the same antipsychotic modality or switch to another non-clozapine oral antipsychotic did not show evidence of being beneficial in relapse prevention, suggesting that clozapine should be started instead. This finding, together with existing knowledge of decreased risk of mortality associated with clozapine, challenges current treatment guidelines that recommend clozapine as a third-line treatment, resulting in treatment practices characterised by long delays to clozapine initiation.
Sigrid Jusélius Foundation.
首发精神分裂症患者预防复发的最佳药物治疗方案尚不清楚。我们旨在评估首次复发前后使用的不同治疗策略及其与后续复发风险的关联。
在这项基于人群的队列研究中，我们从芬兰全国医院出院登记处纳入了1996年至2014年间首次发作精神分裂症且住院后复发的个体（年龄≤45岁）。分析纳入了首次住院前一年内未服用抗精神病药物且出院后5年内复发的个体。在首次复发住院前30天和出院后30天评估治疗策略，并分为长效注射剂、氯氮平、非氯氮平口服抗精神病药物单药治疗、非氯氮平口服抗精神病药物联合治疗和未使用抗精神病药物。采用Cox回归模型分析首次复发后2年或直至死亡或数据链接结束（2017年12月31日）基于治疗类型的第二次复发风险的调整风险比（aHR）。有精神分裂症生活经历的人未参与研究和撰写过程。
在1996年1月31日至2017年12月31日期间，3000名个体首次出现精神病复发且符合分析条件。平均年龄为30.0岁（标准差7.6），1069名（35.6%）患者为女性，1931名（64.4%）为男性。没有种族数据。2148名（71.7%）在2年内出现第二次复发。在首次复发前，大多数个体要么未使用抗精神病药物（n = 1366 [45.5%]），要么使用非氯氮平口服抗精神病药物单药治疗（n = 973 [32.4%]）。与继续使用首次复发前相同的治疗策略相比，与继续任何非氯氮平口服抗精神病药物单药治疗相比，改用氯氮平与第二次复发风险最低相关（aHR 0.66，95%CI 0.49 - 0.89；口服非氯氮平抗精神病药物单药治疗持续使用的复发率为73.2%，改用氯氮平的复发率为57.1%）。改用另一种非氯氮平口服抗精神病药物单药治疗（0.99，0.76 - 1.28）在预防下次复发方面与改用未使用抗精神病药物（1.07，0.80 - 1.42）大致同样无益。
在首发精神分裂症患者中，尽管使用了非氯氮平口服抗精神病药物仍首次出现精神病复发，继续使用相同的抗精神病药物模式或改用另一种非氯氮平口服抗精神病药物在预防复发方面未显示出有益证据，这表明应改为使用氯氮平。这一发现与现有的关于氯氮平降低死亡风险的知识一起，对当前推荐氯氮平作为三线治疗的治疗指南提出了挑战，导致治疗实践中氯氮平起始使用存在长时间延迟的特点。
西格丽德·尤塞利乌斯基金会。
