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

**Authors:** Lorenzo Pelizza, Emanuela Leuci, Emanuela Quattrone, Alessandro Di Lisi, Derna Palmisano, Simona Pupo, Giuseppina Paulillo, Clara Pellegrini, Pietro Pellegrini, Marco Menchetti

PMC · DOI: 10.1111/eip.70167 · Early Intervention in Psychiatry · 2026-03-22

## TL;DR

This study finds that low doses of antipsychotics in youths at risk for psychosis may improve symptoms, while high doses are linked to worse outcomes.

## Contribution

The study identifies distinct clinical outcomes based on low versus high antipsychotic dosing in youths at clinical high risk for psychosis.

## Key findings

- High-dose antipsychotic users had increased hospitalization risk and worse functional outcomes.
- Low-dose antipsychotic users showed better symptomatic remission and less self-harm behavior.
- Antipsychotic dosage is linked to divergent prognostic outcomes in clinical high-risk youths.

## Abstract

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.

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.

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.

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.

## Linked entities

- **Diseases:** psychosis (MONDO:0005485)

## Full-text entities

- **Diseases:** Depression (MESH:D003866), medical disease (MESH:D000069279), PANSS (MESH:C538175), functioning disability (MESH:D003291), self-harm (MESH:D012652), CHR (MESH:D000075902), PDD (MESH:D020773), weight gain (MESH:D015430), -P (MESH:D002972), Schizophrenia (MESH:D012559), APS (MESH:C538265), extrapyramidal (MESH:D001480), overt psychotic episode (MESH:C580065), suicidal ideation (MESH:D001072), motor disorders (MESH:D000068079), CHR-P (MESH:D011618), intellectual disability (MESH:D008607)
- **Chemicals:** risperidone (MESH:D018967), APs (MESH:D000250)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC13006195/full.md

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Source: https://tomesphere.com/paper/PMC13006195