Kinon Bruce J, Chen Lei, Ascher-Svanum Haya, Stauffer Virginia L, Kollack-Walker Sara, Sniadecki Jennifer L, Kane John M
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Schizophr Res. 2008 Jul;102(1-3):230-40. doi: 10.1016/j.schres.2008.02.021. Epub 2008 Apr 18.
To test whether early onset of response to antipsychotic medications accurately predicts subsequent response in the treatment of patients with schizophrenia.
We used data from 5 randomized, double-blind clinical trials comparing olanzapine with other atypical antipsychotic drugs in the treatment of patients with schizophrenia and related disorders, who were at least moderately ill at baseline and who were treated for a minimum of 2 weeks (N=1077). Early response was defined as >or=20% improvement on the PANSS total score at 2 weeks. Conditional probabilities (sensitivity, specificity, positive and negative predictive values) were used to characterize the likelihood of "subsequent response" to treatment (i.e., >or=40% improvement on the PANSS total score with treatment up to 3 months). Subsequent analyses focused on varying thresholds of subsequent response, and at different time points.
Most (80%) of subsequent non-responders by 3 months were correctly classified as early non-responders at 2 weeks (high specificity), and 84% of early non-responders at 2 weeks were subsequent non-responders by 3 months (high negative predictive value). For early responders, prediction of subsequent response was substantially lower. A higher threshold (e.g., >or=40% improvement) had greater predictive accuracy at all time points measured. Early non-responders attained less symptom improvement overall, and were more likely to discontinue from treatment.
Early non-response to antipsychotic medications was a robust predictor of subsequent lack of response in the treatment of patients with schizophrenia. Evaluating patients as early as 2 weeks in treatment can help identify non-responders who may benefit from an alternative therapeutic approach.
检验抗精神病药物治疗的早期反应是否能准确预测精神分裂症患者后续的治疗反应。
我们使用了5项随机、双盲临床试验的数据，这些试验比较了奥氮平与其他非典型抗精神病药物治疗精神分裂症及相关障碍患者的疗效，这些患者在基线时至少病情中度，且接受了至少2周的治疗（N = 1077）。早期反应定义为2周时阳性和阴性症状量表（PANSS）总分改善≥20%。使用条件概率（敏感性、特异性、阳性和阴性预测值）来描述治疗“后续反应”的可能性（即治疗至3个月时PANSS总分改善≥40%）。后续分析聚焦于后续反应的不同阈值以及不同时间点。
到3个月时大多数（80%）后续无反应者在2周时被正确分类为早期无反应者（高特异性），2周时84%的早期无反应者到3个月时为后续无反应者（高阴性预测值）。对于早期反应者，对后续反应的预测则低得多。在所有测量的时间点，较高的阈值（如改善≥40%）具有更高的预测准确性。早期无反应者总体症状改善较少，且更有可能停药。
抗精神病药物治疗的早期无反应是精神分裂症患者后续治疗无反应的有力预测指标。在治疗2周时对患者进行评估有助于识别可能从替代治疗方法中获益的无反应者。
