The place of risperidone in situ microparticles (ISM®) among long-acting injectable antipsychotics in schizophrenia treatment

Abstract

Introduction: A key challenge in managing schizophrenia is ensuring adequate adherence to antipsychotic treatment. Long-acting injectable (LAI) antipsychotics play a crucial role in improving adherence, yet certain clinical needs remain unmet, including a rapid symptom control and satisfactory efficacy/tolerability balance.

Areas covered: Main pharmacokinetics and pharmacodynamics properties as well as the effectiveness and safety profile of risperidone in situ microparticles (ISM®) are described. The aim of this narrative review is to explore how this innovative risperidone LAI formulation may be utilized in schizophrenia treatment.

Expert opinion: Risperidone ISM® employs innovative in situ microimplant technology for biphasic drug release, achieving immediate and sustained therapeutic plasma concentrations without the need for oral supplementation or loading doses. Indeed, it is characterized by a fast-acting release, reaching active risperidone moiety levels within 12 hours that are comparable to steady-state concentrations observed with oral risperidone (mean concentration of 38.63 ng/mL). The resulting plasma levels ensure consistent dopamine D₂ receptor occupancy above 65% over the full 28-day dosing cycle - an established benchmark for antipsychotic efficacy. In the short-term, risperidone ISM® enables a rapid and sustained symptoms reduction among adults with acute schizophrenia exacerbations, eliminating the need for initial loading doses or concurrent oral supplementation.

Keywords: Antipsychotic; depot formulation; long-acting injectable (LAI); pharmacodynamic; pharmacokinetic; psychotic disorders; risperidone; schizophrenia and related disorders.