Real-World Effectiveness and Safety of Antipsychotics in Individuals at Clinical High-Risk for Psychosis: Study Protocol for a Prospective Observational Study (ShangHai at Risk for Psychosis-Phase 2)

Abstract

Background

The clinical high-risk (CHR) state is identified as a critical period for early prevention and intervention during the development of psychosis and early treatment may reduce the risk of conversion to psychosis. However, it remains controversial whether antipsychotics are effective in CHR populations. Limited previous randomised controlled trials of antipsychotic treatment of CHR individuals indicated possible short-term efficacy on psychotic symptoms with unclear long-term effects. To answer this question, it is necessary to establish a high-quality real-world cohort study with large sample size to explore the effectiveness and safety of antipsychotics in CHR individuals.

Methods

We plan to consecutively recruit 600 CHR individuals from Shanghai Mental Health Centre in the ongoing SHARP-2 (ShangHai At Risk for Psychosis-Phase 2) project between 2019 and 2022. At baseline, participants will be assessed by the Structured Interview for Prodromal Syndromes, the MATRICS Consensus Cognitive Battery, demographic information, and clinical medication history. They will be followed up in a naturalistic way in which the research team will not prescribe antipsychotics or provide pharmacological consultation. First, CHR participants and their families will be trained to record their medication daily and self-evaluate symptoms through smart-phone application-based assessment and report their information weekly. Second, telephone calls will be arranged monthly so that the researchers are informed about the participants’ symptoms, medications and daily functions. Third, face-to-face interviews will be conducted annually for repeating assessment of baseline. The primary outcomes will include conversion to psychosis and functional outcome (scored with less than 60 in the Global Assessment of Function) at the end of the follow-up period.

Conclusion

The current study will improve our knowledge on the effectiveness and safety of the use of antipsychotics at the prodromal phase, and will eventually facilitate optimisation of individualised interventions for psychosis prevention and treatment.

Keywords:

• clinical high-risk
• early interventions
• antipsychotics
• subgroup

Trial Status

This trial (Clinicaltrials.gov identifier NCT04010864) was registered on July 4, 2019, and is currently recruiting participants. Outcome results are expected at the end of 2022.

Abbreviations

CGI, Clinical General Impression; CHR, clinical high risk; GAF, Global Assessment of Function score; HAMA, Hamilton Anxiety Scale; HAMD-17, Hamilton Depression Scale-17; MCCB, MATRICS Consensus Cognitive Battery; MINI, Mini-International Neuropsychiatric Interview; RFS, Role Function Scale; SFS, Social Function Scale; SHARP, ShangHai At Risk for Psychosis; SHARP-2, ShangHai At Risk for Psychosis-Phase 2; SIPS/SOPS, Structured Interview for Prodromal Syndromes/Scale of Prodromal Symptoms; SMHC, Shanghai Mental Health Center; SPPCC, Shanghai Psychotherapy and Psychological Counselling Centre; TESS, NIMH-developed Treatment Emergent Symptom Scale; WAIS-RC, Wechsler Adult Intelligence Scale - Revised China.

Author Contributions

All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Funding

This study was supported by Ministry of Science and Technology of China, National Key R&D Program of China (2016YFC1306803), National Natural Science Foundation of China (81671329, 81671332), Shanghai Key Laboratory of Psychotic Disorders (13dz2260500), Science and Technology Commission of Shanghai Municipality (19441907800), Shanghai Jiaotong University Foundation (ZH2018ZDB03), The Clinical Research Center at Shanghai Mental Health Center (CRC2018ZD01, CRC2018ZD04 and CRC2018YB01), Shanghai Mental Health Center Foundation (2016-FX-01, 2017-TSXK-03).

Disclosure

The authors report no conflicts of interest in this work.