Clinical Utility of Long-Acting Injectable Risperidone in Schizophrenia and Bipolar I Disorder: A Review of Clinical Studies

Risperidone was the first second-generation antipsychotic to be developed as a long-acting injectable (LAI). In the early 2000s, a risperidone microsphere formulation, intramuscularly administered every 2 weeks (BW-RLAI), was introduced. To date, five different risperidone LAI formulations have been marketed – including a second biweekly microsphere injection (LY03004), a newer monthly intramuscular formulation using in situ microparticles (ISM) technology that does not require an oral risperidone run-in, and two subcutaneous formulations (RBP-7000 and TV-46000). Understanding the advantages and limitations of each option is essential for tailoring treatment regimens based on clinical needs and patient preferences. In this review, with the aim of offering insights for clinical practice and future research, we provide a comprehensive synthesis of the currently available risperidone LAI formulations, examining their efficacy and safety for the treatment of schizophrenia and bipolar I disorder. While evidence supporting the efficacy, tolerability, and safety of risperidone LAI for schizophrenia is available for all marketed formulations to date, advantages for newer formulations, such as longer dosing intervals without oral supplementation, are also reviewed. In addition, although the Food and Drug Administration approved the biweekly LAIs for bipolar I disorder, there is no data on effectiveness of the other risperidone LAI formulations for this indication so far. The variety of the available risperidone LAI options is likely to enable a more personalized treatment approach. To facilitate this, healthcare providers should develop a comprehensive understanding of these formulations to select the most suitable option. While risperidone ISM, RBP-7000, and TV-46000 may enhance treatment feasibility and adherence, further research is needed to build an evidence base comparable to that available for BW-RLAI, particularly in the treatment of BD.