ImportanceEmerging meta-analytical evidence indicates that baseline exposure to antipsychotics is associated with an increased risk of transitioning to psychosis in individuals at clinical high-risk for psychosis (CHR-P) and that such effect is not a result of pretest risk enrichment. However, to maximize its translational utility for prognostic stratification in clinical practice, testing for the potential presence of a dose-response association is crucial.ObjectiveTo test whether the negative prognostic effect of baseline antipsychotic exposure in individuals at CHR-P follows a dose-effect pattern, as indicated by mean chlorpromazine equivalent doses (CPZ-ED).Data SourcesMEDLINE and Cochrane Library, performed up to August 31, 2023, searching for English-language studies on individuals at CHR-P reporting data on exposure to antipsychotics at baseline and detailed information on dosage by transition status.Study SelectionStudies that provided information on antipsychotic exposure at baseline and included detailed dosage data categorized by transition status.Data Extraction and SynthesisEligible studies were identified following PRISMA guidelines and evaluated independently by 2 reviewers with the Newcastle-Ottawa Scale for assessing the quality of nonrandomized studies in meta-analyses.Main Outcomes and MeasuresThe primary outcome was transition to psychosis in individuals at CHR-P who were receiving antipsychotic treatment at baseline, measured by baseline mean CPZ-ED in individuals at CHR-P who transitioned to psychosis compared to those who did not.ResultsEight studies were included in the systematic review and meta-analysis. Among 290 individuals at CHR-P (mean [SD] age, 19.4 [2.6] years) who were exposed to antipsychotics at baseline and remained in contact up to the completion of the study, 66 converted to psychosis and 224 did not. The mean CPZ-ED ranged 60 to 395 mg/d in those who converted and 13 to 224 mg/d in those who did not. Those who converted to psychosis had higher CPZ-ED than those who did not in both the common-effects model (Hedges g, 0.41; 95% CI, 0.12-0.70; z, 2.78; P = .005) and in the random-effects model (Hedges g, 0.41; 95% CI, 0.15-0.67; z, 3.69; P = .008; τ2, 0.0). There was no relevant heterogeneity (Cochran Q, 3.99; df, 7; P = .78; I2, 0.0%; 95% CI, 0.0-68.0). The radial plot indicated a good fit of the model.Conclusions and RelevanceIn individuals at CHR-P who were exposed to antipsychotics at baseline, those receiving higher antipsychotic doses demonstrated an increased likelihood of transitioning to psychosis. This meta-analytic evidence of putative dose-effect association confirms that baseline antipsychotic exposure and the corresponding dosage carry salient prognostic information that could improve current CHR-P criteria-based risk stratification at inception.

中文翻译：

---

临床高危个体的基线抗精神病药物剂量和向精神病的转变

重要性新出现的荟萃分析证据表明，基线接触抗精神病药物与临床精神病高风险个体（CHR-P）转变为精神病的风险增加相关，并且这种效应并不是预测试风险丰富的结果。然而，为了最大限度地提高其在临床实践中预后分层的转化效用，测试是否存在剂量反应关联至关重要。 目的测试 CHR-P 个体基线抗精神病药物暴露的负面预后效应是否遵循剂量效应模式，如平均氯丙嗪当量剂量 (CPZ-ED) 所示。数据源MEDLINE 和 Cochrane 图书馆，截至 2023 年 8 月 31 日，检索 CHR-P 中个体的英语研究报告基线和抗精神病药物暴露数据按过渡状态划分的剂量的详细信息。研究选择研究提供了基线时抗精神病药物暴露的信息，并包括按过渡状态分类的详细剂量数据。数据提取和合成符合条件的研究是按照 PRISMA 指南确定的，并由 2 位评价者使用纽卡斯尔-渥太华量表独立评估用于评估荟萃分析中非随机研究的质量。主要结果和测量主要结果是在基线时接受抗精神病药物治疗的 CHR-P 个体向精神病的转变，通过 CHR-P 个体的基线平均 CPZ-ED 进行测量与那些没有转变为精神病的人相比。结果 系统评价和荟萃分析中纳入了八项研究。在 290 名 CHR-P 个体（平均 [SD] 年龄，19.4 [2.6] 岁）中，他们在基线时接触过抗精神病药物，并在研究完成前保持接触，其中 66 人转化为精神病，224 人没有转化为精神病。转化者的平均 CPZ-ED 范围为 60 至 395 毫克/天，未转化者的平均 CPZ-ED 范围为 13 至 224 毫克/天。在共同效应模型中，那些转变为精神病的人比那些没有转变为精神病的人具有更高的 CPZ-ED（HedgesG, 0.41; 95% CI，0.12-0.70；z，2.78；磷= .005) 和随机效应模型 (HedgesG, 0.41; 95% CI，0.15-0.67；z，3.69；磷= .008； τ2, 0.0)。不存在相关的异质性（Cochran问，3.99；df, 7;磷= .78；我2, 0.0%; 95% CI，0.0-68.0）。放射状图表明模型拟合良好。结论和相关性在 CHR-P 中，在基线时接触过抗精神病药物的个体中，接受较高剂量抗精神病药物的个体表现出转变为精神病的可能性增加。这种推定剂量效应关联的荟萃分析证据证实，基线抗精神病药物暴露和相应剂量具有显着的预后信息，可以改善当前基于 CHR-P 标准的风险分层。