Translating Pharmacokinetics and Pharmacodynamics into Clinical Decision-Making: A Practical Guide to the Use of Risperidone ISM® in Schizophrenia

Nonadherence to medications for psychosis is a major challenge in the management of schizophrenia and is associated with an increased risk of relapse, hospitalization, functional deterioration, and premature death. Although long-acting injectable (LAI) medications for psychosis improve treatment continuity, important differences exist among LAIs regarding initiation regimen, attainment of therapeutic blood level exposure, and steady state, dosing, and switching. Risperidone ISM® is an intramuscular LAI administered every four weeks, designed to provide rapid and sustained therapeutic exposure without the need for loading doses or oral supplementation. This narrative review translates the pharmacokinetic (PK) and pharmacodynamic (PD) profile of risperidone ISM® into expert-informed guidance for treatment initiation, dose optimization, switching, and ongoing schizophrenia management. Risperidone ISM® achieves therapeutic exposure within hours of administration and maintains plasma concentrations and dopamine D2 receptor occupancy at levels associated with antipsychotic efficacy throughout the dosing interval, supporting continuous antipsychotic coverage and stability. Its PK profile, as characterized in clinical studies, and simplified initiation regimen may facilitate clinical decision-making across treatment settings, including transitions from oral risperidone or other medications for psychosis and continuity of care following hospitalization or relapse, while supporting symptom stability, functioning, and patient engagement. By translating PK/PD characteristics into practical clinical implications, this review aims to support clinicians in optimizing the use of risperidone ISM® as part of individualized, recovery-oriented care in the short- and long-term management of people living with schizophrenia across settings. The recommendations presented reflect expert interpretation of the available PK/PD, clinical trial, observational, and product-label evidence, supplemented by clinical experience.