# The antipsychotics functional index (AFI) in schizophrenia

**Authors:** Gabriel-Cristian Marinescu, Petru Iulian Ifteni, Andreea Teodorescu, Radu Georgescu

PMC · DOI: 10.3389/fphar.2025.1591763 · Frontiers in Pharmacology · 2025-07-02

## TL;DR

This paper introduces a new index to help choose antipsychotics that improve functionality in schizophrenia patients.

## Contribution

The novel Antipsychotics Functional Index (AFI) ranks antipsychotics based on pharmacodynamics, administration frequency, and safety.

## Key findings

- Aripiprazole LAI administered every 2 months ranks highest in the AFI due to its D2 partial agonist mechanism and long administration interval.
- Paliperidone LAI administered every 6 months ranks second due to its infrequent administration schedule.
- Second-generation LAI antipsychotics are generally most favorable for patient functionality according to the AFI.

## Abstract

Schizophrenia can lead to significant and long-lasting deficits in patient functionality. The present study proposes a theoretical index that predicts the ability of an antipsychotic to improve the functionality of patients with schizophrenia. An advantage of this theoretical index is that it directly compares 29 first- and second-generation antipsychotics. This theoretical index, named the Antipsychotics Functional Index (AFI), was constructed considering factors such as pharmacodynamics, pharmacokinetics, pharmaceutical form, ease of administration, and safety aspects. A good antipsychotic ranking based on the proposed index results from combining the partial dopaminergic agonist mechanism and a lower frequency of administration. The top-ranked antipsychotic is aripiprazole long-acting injection (LAI) administered every 2 months, 6 weeks, or 1 month, which is the only antipsychotic D2 partial agonist with an LAI formulation. It is followed by paliperidone LAI administered every 6 months. This antipsychotic has the least frequent administration schedule. According to the AFI, the most favorable antipsychotics for functionality are generally second-generation LAI antipsychotics. The D2 partial agonist mechanism has a pharmacodynamic advantage. Based on this functionality index, psychiatrists could select the most suitable antipsychotic for each patient, with the ultimate goal of helping the patient achieve their maximum potential.

## Linked entities

- **Chemicals:** aripiprazole (PubChem CID 60795), paliperidone (PubChem CID 115237)
- **Diseases:** schizophrenia (MONDO:0005090)

## Full-text entities

- **Diseases:** Schizophrenia (MESH:D012559)
- **Chemicals:** dopaminergic (MESH:D004298), paliperidone (MESH:D000068882), aripiprazole (MESH:D000068180)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC12264984/full.md

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Source: https://tomesphere.com/paper/PMC12264984