Department of Child and Adolescent Psychiatry and Behavioral Sciences, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
J Child Adolesc Psychopharmacol. 2021 Feb;31(1):46-52. doi: 10.1089/cap.2020.0030. Epub 2020 Jul 1.
We investigated the time course of clinical response in the Treatment of Early Onset Schizophrenia Spectrum Disorders Study (TEOSS). TEOSS randomized 119 predominantly outpatient youth ages 8-19 years with schizophrenia or schizoaffective disorder to 8 weeks of treatment with molindone, risperidone, or olanzapine. We used proportional hazards regression to determine whether these three antipsychotics differed in the time until clinical response, defined as the time from treatment initiation to the point of achieving a Clinical Global Impressions-Improvement (CGI-I) scale score of 1 ("very much improved") or 2 ("much improved") that was maintained until week 8. Of the 116 youth who initiated treatment, 56 (48%) achieved clinical response. Among clinical responders, the median (±interquartile range) time until clinical response was 4.0 (±4.0) weeks for olanzapine, 4.5 (±4.0) weeks for risperidone, and 6.0 (±4.0) weeks for molindone. There were no significant differences in time course for clinical response between medications ( = 0.84). Youth without symptom improvement (CGI-I ≥ 4) after 3 weeks were more likely to be clinical nonresponders at week 8 (relative risk ratio = 1.98, 95% confidence interval 1.29-3.05), compared with youth with at-least-minimal symptom improvement after 3 weeks when looking at all antipsychotics combined. To our knowledge, our study is the first to investigate medication differences in treatment response timing in early onset schizophrenia spectrum disorders. Clinical response times for molindone, risperidone, and olanzapine were not significantly different. Furthermore, while lack of early improvement predicted clinical nonresponse, whether or not to continue antipsychotic treatment after 3 or more weeks without symptom improvement should be based on clinical judgment after weighing potential risks, benefits, and alternatives. ClinicalTrials.gov Identifier: NCT00053703.
我们研究了在早期发病的精神分裂症谱系障碍治疗研究(TEOSS)中临床反应的时间过程。TEOSS 将 119 名主要为门诊的 8-19 岁精神分裂症或分裂情感障碍患者随机分为 8 周的莫林酮、利培酮或奥氮平治疗。我们使用比例风险回归来确定这三种抗精神病药物在达到临床总体印象改善(CGI-I)评分 1(“非常改善”)或 2(“明显改善”)的时间上是否存在差异,该评分持续至第 8 周。在开始治疗的 116 名青少年中,有 56 名(48%)达到了临床反应。在临床反应者中,达到临床反应的中位数(±四分位间距)时间分别为奥氮平 4.0(±4.0)周、利培酮 4.5(±4.0)周和莫林酮 6.0(±4.0)周。药物之间在临床反应的时间过程上没有显著差异(p=0.84)。在第 3 周时没有改善症状(CGI-I≥4)的青少年在第 8 周时更有可能成为临床无反应者(相对风险比=1.98,95%置信区间 1.29-3.05),与第 3 周时至少有最小症状改善的青少年相比,无论使用哪种抗精神病药物,在所有药物综合考虑时都是如此。据我们所知,我们的研究是第一个研究早期发病的精神分裂症谱系障碍中治疗反应时间的药物差异的研究。莫林酮、利培酮和奥氮平的临床反应时间没有显著差异。此外,虽然早期改善不足预测临床无反应,但在 3 周或更长时间没有症状改善后是否继续抗精神病药物治疗,应该在权衡潜在风险、获益和替代方案后,根据临床判断来决定。ClinicalTrials.gov 标识符:NCT00053703。