Early non-response as a predictor of later non-response to antipsychotics in schizophrenia: a randomized trial
Yujun Long,
Qiongqiong Wu,
Ye Yang,
Jingda Cai,
Jingmei Xiao,
Zhaoqian Liu,
Yifeng Xu,
Ying Chen,
Manli Huang,
Ruiguo Zhang,
Xijia Xu,
Jian Hu,
Zhifen Liu,
Fang Liu,
Yingjun Zheng,
Huaqing Meng,
Zhimin Wang,
Yanqing Tang,
Xueqin Song,
Yunchun Chen,
Xueyi Wang,
Tiebang Liu,
Xiaoli Wu,
Maosheng Fang,
Chunling Wan,
Jingping Zhao,
Renrong Wu
Affiliations
Yujun Long
Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University
Qiongqiong Wu
Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University
Ye Yang
Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University
Jingda Cai
Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University
Jingmei Xiao
Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University
Zhaoqian Liu
Department of Clinical Pharmacology, Xiangya Hospital, Central South University
Yifeng Xu
Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
Ying Chen
Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University
Manli Huang
Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine
Ruiguo Zhang
Department of Psychiatry, Xijing Hospital, Air Force Military Medical University
Xijia Xu
Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing Brain Hospital
Jian Hu
Department of Psychiatry, The First Affiliated Hospital of Harbin Medical University
Zhifen Liu
Department of Psychiatry, The First Hospital of Shanxi Medical University
Fang Liu
Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University
Yingjun Zheng
Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University
Huaqing Meng
Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University
Zhimin Wang
The National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University
Yanqing Tang
Department of Psychiatry, the First Hospital of China Medical University
Xueqin Song
Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University
Yunchun Chen
Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University
Xueyi Wang
Department of Psychiatry, First Hospital of Hebei Medical University
Tiebang Liu
Department of Psychiatry, Shenzhen Kangning Hospital
Xiaoli Wu
Department of Psychiatry, The Third Affiliated Hospital, Sun Yat-Sen University
Maosheng Fang
Wuhan Mental Health Center
Chunling Wan
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University
Jingping Zhao
Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University
Renrong Wu
Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University
Abstract Background It remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia. Methods This multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a < 20% reduction in the total scores of PANSS from baseline to endpoint. Severity ratings of mild, moderate, and severe illness corresponded to baseline PANSS total scores of 58, 75, and 95, respectively. Results At week 2, a reduction of < 5% in the PANSS total score showed the highest total accuracy in the severe and mild schizophrenia patients (total accuracy, 75.0% and 80.8%, respectively), and patients who were treated with the risperidone and amisulpride groups (total accuracy, 82.4%, and 78.2%, respectively). A 10% decrease exhibited the best overall accuracy in the moderate schizophrenia patients (total accuracy, 84.0%), olanzapine (total accuracy, 79.2%), and aripiprazole group (total accuracy, 77.4%). At week 4, the best predictive cut-off value was < 20%, regardless of the antipsychotic or severity of illness (total accuracy ranging from 89.8 to 92.1%). Conclusions Symptom reduction at week 2 has acceptable discrimination in predicting later non-response to antipsychotics in schizophrenia, and a more accurate predictive cut-off value should be determined according to the medication regimen and baseline illness severity. The response to treatment during the next 2 weeks after week 2 could be further assessed to determine whether there is a need to change antipsychotic medication during the first four weeks. Trial registration This study was registered on Clinicaltrials.gov (NCT03451734).
