BACKGROUND Patients with psychotic depression exhibit elevated cortisol levels. Competitively antagonizing cortisol at the glucocorticoid receptor with mifepristone demonstrated therapeutic benefit in early studies of patients with psychotic depression. We present a combined analysis of all controlled phase 2 and 3 studies to report antipsychotic differences between treatment with mifepristone or placebo and to evaluate the relative contributions to response of attaining an a priori-defined, high mifepristone plasma level and markers of glucocorticoid receptor antagonism (increases in adrenocorticotropin hormone and cortisol) with treatment. METHODS Data from five similarly designed double-blind phase 2 or 3 studies evaluating the efficacy and safety of 7-day treatment with mifepristone for the psychotic symptoms of psychotic depression were pooled for analysis (mifepristone n = 833; placebo n = 627). Clinical assessments were performed at baseline and on days 7, 14, 28, 42, and 56. Mifepristone, adrenocorticotropin hormone, and cortisol samples were collected at baseline and day 7. RESULTS Combined results demonstrated meaningful efficacy (p < .004) for mifepristone in reducing psychotic symptoms with wide safety margins. Patients in the a priori-defined, high mifepristone plasma level group (≥1637 ng/mL) demonstrated a more significant treatment effect over placebo (p = .0004). A number needed to treat of 7 and 48 was observed in the high and low mifepristone plasma level groups, respectively. Adverse events were similar in mifepristone- and placebo-treated patients. CONCLUSIONS A high mifepristone plasma level carried the strongest association with response, followed by changes in adrenocorticotropin hormone and cortisol. Therapeutic plasma levels of mifepristone were most likely to be achieved with the 1200 mg/day dose.

中文翻译：

---

米非司酮治疗精神病性抑郁症的综合分析 与临床反应相关的血浆水平

背景精神病性抑郁症患者表现出升高的皮质醇水平。在精神病性抑郁症患者的早期研究中，用米非司酮竞争性拮抗糖皮质激素受体的皮质醇显示出治疗益处。我们对所有对照的 2 期和 3 期研究进行了综合分析，以报告米非司酮或安慰剂治疗之间抗精神病药的差异，并评估达到先验定义的高米非司酮血浆水平和糖皮质激素受体拮抗剂标志物对反应的相对贡献。肾上腺皮质激素和皮质醇的增加）治疗。方法 将来自五项类似设计的双盲 2 或 3 期研究的数据汇总起来进行分析（米非司酮 n = 833；安慰剂 n = 627），这些研究评估了 7 天米非司酮治疗对精神病性抑郁症的精神病症状的疗效和安全性。在基线和第 7、14、28、42 和 56 天进行临床评估。在基线和第 7 天收集米非司酮、促肾上腺皮质激素和皮质醇样本。结果 综合结果表明米非司酮具有有意义的疗效 (p < .004)以广泛的安全边际减少精神病症状。先验定义的高米非司酮血浆水平组 (≥1637 ng/mL) 中的患者表现出比安慰剂更显着的治疗效果 (p = .0004)。在高和低米非司酮血浆水平组中观察到需要治疗的人数为 7 和 48，分别。米非司酮和安慰剂治疗患者的不良事件相似。结论 高米非司酮血浆水平与反应的相关性最强，其次是促肾上腺皮质激素和皮质醇的变化。1200 毫克/天的剂量最有可能达到米非司酮的治疗血浆水平。