Optimizing and Individualizing the Pharmacological Treatment of First-Episode Schizophrenic Patients: Study Protocol for a Multicenter Clinical Trial

Abstract

Introduction: Affecting ~1% of the world population, schizophrenia is known as one of the costliest and most burdensome diseases worldwide. Antipsychotic medications are the main treatment for schizophrenia to control psychotic symptoms and efficiently prevent new crises. However, due to poor compliance, 74% of patients with schizophrenia discontinue medication within 1.5 years, which severely affects recovery and prognosis. Through research on intra and interindividual variability based on a psychopathology-neuropsychology-neuroimage-genetics-physiology-biochemistry model, our main objective is to investigate an optimized and individualized antipsychotic-treatment regimen and precision treatment for first-episode schizophrenic patients. Methods and Analysis: The study is performed in 20 representative hospitals in China. Three subprojects are included. In subproject 1, 1,800 first-episode patients with schizophrenia are randomized into six different antipsychotic monotherapy groups (olanzapine, risperidone, aripiprazole, ziprasidone, amisulpride, and haloperidol) for an 8-week treatment. By identifying a set of potential biomarkers associated with antipsychotic treatment response, we intend to build a prediction model, which includes neuroimaging, epigenetics, environmental stress, neurocognition, eye movement, electrophysiology, and neurological biochemistry indexes. In subproject 2, apart from verifying the prediction model established in subproject 1 based on an independent cohort of 1,800 first-episode patients with schizophrenia, we recruit patients from a verification cohort who did not get an effective response after an 8-week antipsychotic treatment into a randomized double-blind controlled trial with minocycline (200 mg per day) and sulforaphane (3 tables per day) to explore add-on treatment for patients with schizophrenia. Two hundred forty participants are anticipated to be enrolled for each group. In subproject 3, we tend to carry out one trial to construct an intervention strategy for metabolic syndrome induced by antipsychotic treatment and another one to build a prevention strategy for patients at a high risk of metabolic syndrome, which combines metformin and lifestyle intervention. Two hundred participants are anticipated to be enrolled for each group. Ethics and Dissemination: The study protocol has been approved by the Medical Ethics committee of the Second Xiangya Hospital of Central South University (No. 2017027). Results will be disseminated in peer-reviewed journals and at international conferences. Trial Registration: This trial has been registered on Clinicalrials.gov (NCT03451734). The protocol version is V.1.0 (April 23, 2017).

Keywords: biomarker; efficacy and adverse effects; first-episode schizophrenic patients; metabolic syndrome; optimized and individualized treatment.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Xiao, Huang, Long, Wang, Wang, Yang, Hei, Sun, Zhao, Li, Shao, Wang, Kang, Liu, Xie, Huang, Wu and Zhao.

Figures

Figure 1

Study flow diagram. In subproject 1, after recruitment and eligibility checks, 1,800 participants will be randomized into six monotherapy groups. Through an 8-week multidimensional evaluation, we will screen potential biomarkers and build a prediction model. Then, the verification part and add-on treatment will be carried out in subproject 2. Finally, we will conduct a randomized double-blind controlled trial to summarize a comprehensive intervention strategy for metabolic syndrome (MetS).

Figure 2

Cognitive domains and corresponding tests. The Chinese version of the MCCB and four supplementary cognitive tests will be used to assess eight cognitive domains as follows: (1) processing speed; (2) attention/vigilance; (3) working memory; (4) verbal learning and memory; (5) visual learning and memory; (6) reasoning and problem solving; (7) social cognition; and (8) executive function.