Quantitative Sciences, 920 Rt. 202, Janssen Research & Development, Raritan, NJ 08869, United States.
Neurosciences, Janssen Research & Development, 1800 American Boulevard, Pennington, NJ, 08534, United States.
Schizophr Res. 2018 Nov;201:324-328. doi: 10.1016/j.schres.2018.05.028. Epub 2018 May 24.
Antipsychotic blood levels (ABLs) may help identify patients at risk for treatment failure. Reference ranges (RR) for plasma concentrations of ABLs that account for between-patient variability were developed for risperidone and olanzapine based on population pharmacokinetic models. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) collected clinical outcomes and ABLs, allowing testing of the relationship of ABLs with outcomes.
ABLs from 694 patients who were randomized to olanzapine or risperidone were compared to the 80% RRs and were assessed as below or within/above the RR. Treatment failure was defined per any of these criteria: (1) emergency room visit for psychiatric reasons, (2) hospitalization for psychiatric reasons, (3) adverse event of completed suicide, suicidal ideation, or suicide attempt, (4) assaultive behavior, (5) arrested or jailed, (6) 2-point increase from baseline in Clinical Global Impression-Severity score, (7) 25% increase in Positive and Negative Syndrome Scale total score. Patients assessed with treatment failure within 100 days of drug concentration measurement were analyzed.
Treatment failure occurred in 126 of 323 patients. The proportion of patients with ABLs below RR was 18.3% (59/323) compared to 10% expected in a fully adherent population. Among the 59 with ABLs below RR, 50.8% had treatment failure (compared to 36.4% for the 264 with ABLs within/above RR). The difference between groups was significant (odds ratio = 1.810; 95% CI = 1.025, 3.197; p = 0.0408).
Analysis of CATIE data showed that ABLs within the context of RRs may identify patients with higher risk of relapse.
抗精神病药血药浓度（ABL）可能有助于确定治疗失败风险高的患者。基于群体药代动力学模型，为利培酮和奥氮平开发了考虑患者间变异性的 ABL 血浆浓度参考范围（RR）。临床抗精神病药物干预有效性试验（CATIE）收集了临床结果和 ABL，从而可以检验 ABL 与结果的关系。
比较了随机分配至奥氮平或利培酮的 694 名患者的 ABL 与 80%RR，并将其评估为低于或等于/高于 RR。根据以下任何标准定义治疗失败：（1）因精神原因急诊，（2）因精神原因住院，（3）完成自杀、自杀意念或自杀企图的不良事件，（4）攻击性行为，（5）被捕或入狱，（6）临床总体印象严重程度评分较基线增加 2 分，（7）阳性和阴性综合征量表总分增加 25%。对在药物浓度测量后 100 天内评估为治疗失败的患者进行分析。
323 名患者中有 126 名发生治疗失败。ABL 低于 RR 的患者比例为 18.3%（59/323），而在完全依从人群中预计为 10%。在 59 名 ABL 低于 RR 的患者中，有 50.8%发生治疗失败（相比之下，264 名 ABL 等于/高于 RR 的患者中有 36.4%发生治疗失败）。两组之间的差异具有统计学意义（比值比=1.810；95%置信区间=1.025，3.197；p=0.0408）。
对 CATIE 数据的分析表明，RR 范围内的 ABL 可能可以识别出复发风险较高的患者。
