Randomized Controlled Trial

. 2023 Jul 19;21(1):263.

doi: 10.1186/s12916-023-02968-7.

Early non-response as a predictor of later non-response to antipsychotics in schizophrenia: a randomized trial

Yujun Long^#¹, Qiongqiong Wu^#¹, Ye Yang¹, Jingda Cai¹, Jingmei Xiao¹, Zhaoqian Liu², Yifeng Xu³, Ying Chen⁴, Manli Huang⁵, Ruiguo Zhang⁶, Xijia Xu⁷, Jian Hu⁸, Zhifen Liu⁹, Fang Liu¹⁰, Yingjun Zheng¹¹, Huaqing Meng¹², Zhimin Wang¹³, Yanqing Tang¹⁴, Xueqin Song¹⁵, Yunchun Chen¹⁶, Xueyi Wang¹⁷, Tiebang Liu¹⁸, Xiaoli Wu¹⁹, Maosheng Fang²⁰, Chunling Wan²¹, Jingping Zhao¹, Renrong Wu²²

Affiliations

¹ Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 139# Renmin Middle RD, Changsha, 410011, Hunan, China.
² Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
⁵ Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
⁶ Department of Psychiatry, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi, China.
⁷ Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing Brain Hospital, Nanjing, Jiangsu, China.
⁸ Department of Psychiatry, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
⁹ Department of Psychiatry, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
¹⁰ Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
¹¹ Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
¹² Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
¹³ The National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.
¹⁴ Department of Psychiatry, the First Hospital of China Medical University, Shenyang, Liaoning, China.
¹⁵ Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
¹⁶ Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
¹⁷ Department of Psychiatry, First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
¹⁸ Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen, Guangdong, China.
¹⁹ Department of Psychiatry, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
²⁰ Wuhan Mental Health Center, Wuhan, Hubei, China.
²¹ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
²² Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 139# Renmin Middle RD, Changsha, 410011, Hunan, China. wurenrong@csu.edu.cn.

^# Contributed equally.

PMID: 37468932
PMCID: PMC10354903
DOI: 10.1186/s12916-023-02968-7

Randomized Controlled Trial

Early non-response as a predictor of later non-response to antipsychotics in schizophrenia: a randomized trial

Yujun Long et al. BMC Med. 2023.

. 2023 Jul 19;21(1):263.

doi: 10.1186/s12916-023-02968-7.

Authors

Affiliations

¹ Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 139# Renmin Middle RD, Changsha, 410011, Hunan, China.
² Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
⁵ Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
⁶ Department of Psychiatry, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi, China.
⁷ Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing Brain Hospital, Nanjing, Jiangsu, China.
⁸ Department of Psychiatry, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
⁹ Department of Psychiatry, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
¹⁰ Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
¹¹ Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
¹² Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
¹³ The National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.
¹⁴ Department of Psychiatry, the First Hospital of China Medical University, Shenyang, Liaoning, China.
¹⁵ Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
¹⁶ Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
¹⁷ Department of Psychiatry, First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
¹⁸ Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen, Guangdong, China.
¹⁹ Department of Psychiatry, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
²⁰ Wuhan Mental Health Center, Wuhan, Hubei, China.
²¹ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
²² Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 139# Renmin Middle RD, Changsha, 410011, Hunan, China. wurenrong@csu.edu.cn.

^# Contributed equally.

PMID: 37468932
PMCID: PMC10354903
DOI: 10.1186/s12916-023-02968-7

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).

Keywords: Atypical antipsychotic; Early response; Prediction; Schizophrenia.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Fig. 1**
Flowchart of the study design

**Fig. 2**
Percentage of non-responder to four antipsychotics at endpoint, stratified by baseline illness severity

See this image and copyright information in PMC

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Early non-response as a predictor of later non-response to antipsychotics in schizophrenia: a randomized trial

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Early non-response as a predictor of later non-response to antipsychotics in schizophrenia: a randomized trial

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