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).

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.