Abstract

Objective

To quantify the risk and predictors of relapse among individuals with schizophrenia randomly withdrawn from antipsychotic maintenance treatment.

Methods

We re-analyzed time-to-event and baseline predictors from placebo arms in five placebo-controlled randomized trials of antipsychotics (n = 688 individuals; 173 stabilized on oral antipsychotic [OAP] and 515 on long-acting injectables [LAI]) for relapse-prevention available in the Yale Open Data Access repository. Using a survival and Cox-proportional hazards regression analyses, we estimated survival rates of “relapse-free” individuals by the end of follow-up (median = 118 days, IQR = 52.0–208.0), the rate of study-confirmed relapse, and adjusted hazard ratios (aHR, 95% confidence intervals [CI]) associated with baseline predictors. We also estimated these parameters for individuals followed for >5 half-lives of the stabilizing antipsychotic, and studied predictors of “rebound psychosis” in OAP-stabilized participants, defined as occurring within 30 days of antipsychotic withdrawal.

Results

29.9% (95%CI = 23.2–38.5) remained relapse-free by the end of follow-up, 11.1% (95%CI = 5.65–21.9) among those OAP-stabilized, 36.4% (95%CI = 28.4–46.7) among those LAI-stabilized. The study-confirmed relapse rate was 45.2%, 62.4% among those OAP-stabilized and 39.4% among those LAI-stabilized. Predictors of relapse included smoking (aHR = 1.54, 95%CI = 1.19–2.00), female sex (aHR = 1.37, 95%CI = 1.08–1.79), and having been stabilized on OAPs vs LAIs (aHR = 3.56, 95%CI = 2.68–4.72). Greater risk of relapse on OAP persisted even after sufficient time had elapsed to clear antipsychotic plasma level among LAI-stabilized (aHR = 5.0, 95%CI = 3.5–7.1). “Rebound psychosis” did not show predictors.

Conclusions and relevance

Our results corroborate the high relapse risk following antipsychotic withdrawal after symptom stabilization with limited patient-related predictors of safe treatment discontinuation. Stabilization with LAIs reduces the short-/medium-term relapse risk.

中文翻译：

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临床稳定的精神分裂症患者随机停用口服和长效注射用抗精神病药后无复发的预测因素：对个体参与者数据的重新分析

摘要

客观的

量化随机退出抗精神病药物维持治疗的精神分裂症患者复发的风险和预测因素。

方法

我们在五项安慰剂对照的抗精神病药物随机试验中重新分析了安慰剂组的事件发生时间和基线预测因子（n= 688 人；耶鲁开放数据访问存储库中提供的用于预防复发的 173 人使用口服抗精神病药 [OAP] 和 515 人使用长效注射剂 [LAI]）。使用生存和 Cox 比例风险回归分析，我们估计了随访结束时“无复发”个体的生存率（中位数 = 118 天，IQR = 52.0-208.0），研究确认的复发率，和与基线预测因子相关的调整后的风险比（aHR，95% 置信区间 [CI]）。我们还估计了稳定抗精神病药物超过 5 个半衰期的个体的这些参数，并研究了 OAP 稳定参与者中“反弹性精神病”的预测因子，定义为在抗精神病药物停药后 30 天内发生。

结果

29.9% (95%CI = 23.2–38.5) 在随访结束时保持无复发，11.1% (95%CI = 5.65–21.9) 在 OAP 稳定的患者中，36.4% (95%CI = 28.4–46.7) ）在那些LAI稳定的。经研究证实的复发率为 45.2%，OAP 稳定者为 62.4%，LAI 稳定者为 39.4%。复发的预测因素包括吸烟（aHR = 1.54, 95%CI = 1.19-2.00）、女性（aHR = 1.37, 95%CI = 1.08-1.79），并且在 OAP 与 LAI 上已经稳定（aHR = 3.56, 95% CI = 2.68–4.72)。即使在 LAI 稳定的患者中经过足够的时间来清除抗精神病药物的血浆水平后，OAP 复发的更大风险仍然存在（aHR = 5.0, 95% CI = 3.5-7.1）。“反弹性精神病”没有显示出预测因素。

结论和相关性

我们的结果证实了症状稳定后抗精神病药物停药后的高复发风险，而与患者相关的安全停药预测因子有限。LAI 的稳定性降低了短期/中期复发风险。