When to initiate antipsychotic treatment for psychotic symptoms: At the premorbid phase or first episode of psychosis?

Abstract

Antipsychotic drugs are widely used for treating patients with first episode of psychosis, targeting threshold psychotic symptoms. The clinical high risk of psychosis is characterized as subthreshold psychotic symptoms and it is unclear whether they can also benefit from antipsychotic drugs treatment. This study attempted to determine whether initiating antipsychotic drugs treatment in the clinical high risk of psychosis phase was superior to initiating antipsychotic drugs treatment in the first episode of psychosis phase, after the 2-year symptomatic and functional outcomes. Drawing on 517 individuals with clinical high risk of psychosis from the ShangHai At Risk for Psychosis program, we identified 105 patients who converted to first episode of psychosis within the following 2 years. Patients who initiated antipsychotic drugs while at clinical high risk of psychosis (CHR_AP; n = 70) were compared with those who initiated antipsychotic drugs during a first episode of psychosis (FEP_AP; n = 35). Summary scores on positive symptoms and the global function scores at baseline and at 2 months, 1 year and 2 years of follow-up were analyzed to evaluate outcomes. The CHR_AP and FEP_AP groups were not different in the severity of positive symptoms and functioning at baseline. However, the CHR_AP group exhibited significantly more serious negative symptoms and total symptoms than the FEP_AP group. Both groups exhibited a significant reduction in positive symptoms and function (p < 0.001). Repeated-measures analysis of variance revealed group by time interaction for symptomatic (F = 3.196, df = 3, p = 0.024) and functional scores (F = 7.306, df = 3, p < 0.001). The FEP_AP group showed higher remission rates than the CHR_AP group (χ2 = 22.270, p < 0.001). Compared to initiating antipsychotic drug treatments in the clinical high risk of psychosis state, initiating antipsychotic drugs treatments in the first episode of psychosis state predicted remission in a regression model for FEP_AP (odds ratio = 5.567, 95% confidence interval = [1.783, 17.383], p = 0.003). For clinical high risk of psychosis, antipsychotic drugs might be not the first choice in terms of long-term remission, which is more reasonable to use at the first episode of psychosis phase.