Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
Cantonal Sociopsychiatric Organisation, Public Health Division, Department of Health and Social Care, Repubblica e Cantone Ticino, Mendrisio, Switzerland.
JAMA Psychiatry. 2024 Jul 1;81(7):727-730. doi: 10.1001/jamapsychiatry.2024.0178.
Emerging 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.
To 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).
MEDLINE 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.
Studies that provided information on antipsychotic exposure at baseline and included detailed dosage data categorized by transition status.
Eligible 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.
The 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.
Eight 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.
In 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.
新兴的荟萃分析证据表明，基线时接触抗精神病药物与临床高风险精神病（CHR-P）个体向精神病转化的风险增加有关，而且这种效应不是预测试风险富集的结果。然而，为了最大限度地提高其在临床实践中的预后分层的转化实用性，测试潜在的剂量-反应关联是至关重要的。
测试在 CHR-P 个体中，基线时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，如平均氯丙嗪等效剂量（CPZ-ED）所示。
截至 2023 年 8 月 31 日，在 MEDLINE 和 Cochrane 图书馆进行了搜索，检索了关于 CHR-P 个体基线时接触抗精神病药物和按过渡状态详细分类剂量的英语研究。
提供基线抗精神病药物暴露信息并包括按过渡状态分类的详细剂量数据的研究。
按照 PRISMA 指南确定符合条件的研究，并由 2 名独立的审阅者使用评估荟萃分析中非随机研究质量的纽卡斯尔-渥太华量表进行评估。
主要结果是在基线时接受抗精神病药物治疗的 CHR-P 个体中向精神病的转变，通过在 CHR-P 个体中从基线 CPZ-ED 测量向精神病转变的个体与未转变的个体进行比较。
系统评价和荟萃分析纳入了 8 项研究。在 290 名接受基线抗精神病药物治疗并在研究完成前保持联系的 CHR-P 个体（平均[SD]年龄，19.4[2.6]岁）中，66 人转化为精神病，224 人未转化。在转化为精神病的个体中，CPZ-ED 的平均值为 60 至 395 毫克/天，而未转化的个体为 13 至 224 毫克/天。在共同效应模型中（Hedges g，0.41；95%置信区间，0.12-0.70；z，2.78；P = 0.005）和随机效应模型中（Hedges g，0.41；95%置信区间，0.15-0.67；z，3.69；P = 0.008；τ2，0.0），转化为精神病的个体的 CPZ-ED 高于未转化的个体。没有相关的异质性（Cochran Q，3.99；df，7；P = 0.78；I2，0.0%；95%置信区间，0.0-68.0）。径向图表明模型拟合良好。
在基线时接受抗精神病药物治疗的 CHR-P 个体中，接受较高抗精神病药物剂量的个体向精神病转化的可能性增加。该荟萃分析证据表明，潜在的剂量-效应关联证实了基线抗精神病药物暴露和相应剂量具有重要的预后信息，可以在当前基于 CHR-P 标准的风险分层初始时提高其预后。
