Treatment-resistant schizophrenia (TRS) is associated with high levels of functional impairment, healthcare usage and societal costs. Cross-sectional studies may overestimate TRS rates because of selection bias.

We aimed to quantify TRS rates by using first-episode cohorts to improve resource allocation and clozapine access.

We undertook a systematic review of TRS rates among people with first-episode psychosis and schizophrenia, with a minimum follow-up of 8 weeks. We searched PubMed, PsycINFO, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews, and meta-analysed TRS rates from included studies.

Twelve studies were included, totalling 11 958 participants; six studies were of high quality. The rate of TRS was 22.8% (95% CI 19.1–27.0%, P < 0.001) among all first-episode cohorts and 24.4% (95% CI 19.5–30.0%, P < 0.001) among first-episode schizophrenia cohorts. Subgroup sensitivity analyses by location of recruitment, TRS definition, study quality, time of data collection and retrospective versus prospective data collection did not lead to statistically significant differences in heterogeneity. In a meta-regression, duration of follow-up and percentage drop-out did not significantly affect the overall TRS rate. Men were 1.57 times more likely to develop TRS than women (95% CI 1.11–2.21, P = 0.010).

Almost a quarter of people with first-episode psychosis or schizophrenia will develop TRS in the early stages of treatment. When including people with schizophrenia who relapse despite initial response and continuous treatment, rates of TRS may be as high as a third. These high rates of TRS highlight the need for improved access to clozapine and psychosocial supports.

难治性精神分裂症 (TRS) 与高水平的功能障碍、医疗保健使用和社会成本相关。由于选择偏倚，横断面研究可能会高估 TRS 率。

我们旨在通过使用首集队列来量化 TRS 率，以改善资源分配和氯氮平的使用。

我们对首发精神病和精神分裂症患者的 TRS 率进行了系统评价，至少随访 8 周。我们检索了 PubMed、PsycINFO、EMBASE、CINAHL 和 Cochrane 系统评价数据库，并对纳入研究的 TRS 率进行了荟萃分析。

纳入 12 项研究，共 11 958 名参与者；六项研究质量很高。在所有首发精神分裂症队列中，TRS 率为 22.8%（95% CI 19.1-27.0%，P < 0.001 ），在首发精神分裂症队列中为24.4%（95% CI 19.5-30.0%，P < 0.001）。按招募地点、TRS 定义、研究质量、数据收集时间以及回顾性与前瞻性数据收集的亚组敏感性分析并未导致异质性的统计学显着差异。在元回归中，随访时间和辍学百分比对总体 TRS 率没有显着影响。男性患 TRS 的可能性是女性的 1.57 倍（95% CI 1.11-2.21，P = 0.010）。

几乎四分之一的首发精神病或精神分裂症患者会在治疗的早期阶段发展为 TRS。如果将精神分裂症患者包括在内，尽管初始反应和持续治疗仍会复发，TRS 的发生率可能高达三分之一。如此高的 TRS 发生率凸显了改善氯氮平和社会心理支持的必要性。