Exposure to Antipsychotics in Youths at Clinical High Risk for Psychosis: Low VS High Doses and Their Relevance for Clinical Outcomes

Introduction: Predicting prognosis in subjects at Clinical High Risk for Psychosis (CHR-P) is still challenging. In particular, there are some disregarded factors such as ongoing Antipsychotic (AP) treatment that potentially induce method errors and research bias. The specific purpose of this examination was to examine whether baseline AP exposure and its dosage identify different CHR-P groups with diverse prognostic outcomes across 2 years of follow-up. Methods: 182 CHR-P participants (93 AP-naïve, 60 low-dose AP, 33 high-dose AP) were assessed for a broad range of clinical outcomes, including psychosis transition, clinical and functional remission (measured with the Positive and Negative Syndrome Scale and the Social and Occupational Functioning Assessment Scale). Inter-group comparisons were explored using Kaplan– Meier survival analyses and binary logistic regression analyses. Results: Across the follow-up, the high-dose AP subgroup showed an increased risk of new hospitalisation and poorer functional remission compared to AP-naïve participants. Conversely, the low-dose AP subsample had a higher 2-year rate of symptomatic remission and a lower 2-year rate of self-harm behaviour compared to AP-naïve one. Conclusion: APs at low doses are associated with better symptomatic outcomes, whilst APs at high doses correlate to poorer socio-occupational functioning. Promoting personalised treatment strategies and facilitating the identification of specific CHR-P subgroups with divergent prognoses are recommended in clinical practise.