Real-world impact of risperidone ISM on healthcare utilization: a multicentre retrospective study

Introduction

Schizophrenia spectrum and related disorders are associated with high relapse rates, functional impairment, and substantial healthcare utilization, largely driven by poor adherence to antipsychotic treatment. Long-acting injectable antipsychotics (LAIs) improve adherence and reduce relapse risk[1]. Risperidone ISM is a novel monthly LAI formulation that achieves rapid therapeutic plasma concentrations without the need for oral supplementation[2], [3]. Real-world evidence is essential to assess its effectiveness and tolerability across heterogeneous clinical populations.

Objectives

To characterize the sociodemographic and clinical profile of patients treated with risperidone ISM, evaluate treatment exposure and tolerability, and assess its impact on healthcare utilization, namely psychiatric hospitalizations and emergency department (ED) visits.

Methods

Retrospective observational multicentre study including patients treated with risperidone ISM across four psychiatric centres in Portugal. Clinical and demographic data were collected from medical records. Treatment exposure was assessed by the number of administered doses. Healthcare utilization was evaluated using a within-subject design, comparing the number of hospitalizations and ED visits in the 12 months before and after treatment initiation.

Results

A total of 155 patients were included, with a mean age of 43.6 years and a predominance of males (60.6%). The majority of patients had schizophrenia spectrum or primary psychotic disorders (approximately 70%), followed by bipolar disorder and other psychiatric conditions. Mean treatment exposure was 9.8 administered doses, reflecting variable follow-up duration in a real-world setting. Results should therefore be considered preliminary, as not all patients completed 12 months of treatment. A subgroup of 48 patients (31%) completed ≥12 months of treatment and was included in the primary effectiveness analysis. In this subgroup, psychiatric hospitalizations decreased from 64 in the 12 months prior to treatment initiation to 8 in the 12 months after, corresponding to an 87.5% reduction. Emergency department visits decreased from 92 to 18, corresponding to an 80.4% reduction. These findings indicate a marked reduction in relapse-related healthcare utilization among patients with sustained exposure to risperidone ISM, suggesting progressive clinical stabilization over time. Regarding safety, risperidone ISM was generally well tolerated. Most patients did not report clinically significant adverse effects. The most frequently reported adverse events included sexual dysfunction, extrapyramidal symptoms (including akathisia and rigidity), and subjective psychomotor slowing. Less frequent events included hyperprolactinaemia with amenorrhoea and oromandibular dyskinesia. Importantly, only 3 patients (1.9%) required treatment discontinuation or switch due to adverse effects, indicating a favourable tolerability profile in real-world clinical practice.

Conclusions

In this multicentre real-world cohort, risperidone ISM was associated with a marked and clinically meaningful reduction in healthcare utilization, including psychiatric hospitalizations and ED visits. The favourable tolerability profile, with a low rate of discontinuation due to adverse effects, further supports its use in routine clinical practice. These findings reinforce the role of risperidone ISM as an effective strategy to improve clinical stability and reduce healthcare burden in patients with psychotic disorders, although the retrospective design and sample heterogeneity should be considered.

References

1. Kishimoto, T., Nitta, M., Borenstein, M., Kane, J. M., & Correll, C. U. (2013). Long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis of mirror-image studies. The Journal of clinical psychiatry, 74(10), 957–965.
2. Walling, D. P., Hassman, H. A., Anta, L., Ochoa, L., Ayani, I., Martínez, J., & Gutierro, I. (2021). The Steady-State Comparative Bioavailability of Intramuscular Risperidone ISM and Oral Risperidone: An Open-Label, One-Sequence Study. Drug design, development and therapy, 15, 4371–4382.
3. Filts, Y., Litman, R. E., Martínez, J., Anta, L., Naber, D., & Correll, C. U. (2022). Long-term efficacy and safety of once-monthly Risperidone ISM® in the treatment of schizophrenia: Results from a 12-month open-label extension study. Schizophrenia research, 239, 83–91.