Objective: The objective of this study was to describe the safety, efficacy, and potential role in therapy of once in 6 months paliperidone palmitate formulation (PP6M; Invega Hafyera). PP6M is a long-acting injectable antipsychotic recently approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia. Data Sources: A PubMed literature search was conducted using the following terms: paliperidone palmitate and long-acting antipsychotic injections (January 1, 2017, to November 1, 2022). FDA product labeling was also reviewed for pertinent data. Study Selection and Data Extraction: All relevant English-language articles focused on the efficacy and safety of PP6M were considered for inclusion. Data Synthesis: A multicenter, randomized, active controlled relapse prevention noninferiority study showed that PP6M is comparable to paliperidone palmitate once in 3 months formulation (PP3M) in terms of efficacy and safety in clinically stable schizophrenia patients. Place in Therapy: PP6M is indicated in the treatment of adult patients with schizophrenia, who need treatment over a prolonged period. It improves adherence and decreases the rate of relapse and hospitalizations among patients with schizophrenia. It is useful for patients who may have difficulty accessing health care or would prefer the convenience of less frequent injections. Conclusion: PP6M with its long duration of action and lowered frequency of administration (once every 6 months) expands the therapeutic choices available to patients with schizophrenia. More studies in patients with schizophrenia with PP6M, and perhaps other mental illnesses (eg, schizoaffective disorder), are required to fully elucidate the therapeutic potential of PP6M.

Introduction: Paliperidone Palmitate is the only antipsychotic that has been developed in three different intramuscular long-acting injectable (LAI) dosing regimen: monthly (PP1M), quarterly (PP3M), and from 2020 also twice-yearly (PP6M). The latter was approved for the maintenance treatment of adults with schizophrenia and clinically stabilized with PP1M or PP3M.

Areas covered: Data from studies evaluating efficacy in the maintenance treatment of schizophrenia with PP6M are reviewed. Since no post-marketing safety studies are currently available, data from spontaneous reporting system databases, FAERS and Eudravigilance, are analyzed and the reported treatment-emergent adverse events of PP6M are discussed.

Expert opinion: The efficacy of PP6M is comparable to that of PP3M in terms of relapses prevention in patients with schizophrenia previously stabilized on PP3M or PP1M. Also, the maintenance of clinical efficacy in the long term has been demonstrated. Data from pharmacovigilance analyses, as well as from phase 3 studies, show that PP6M is generally well tolerated, consistently with PP3M safety data. PP6M allows a longer dosing interval than any other LAI antipsychotics, potentially reducing nonadherence and disease relapses. In future, an increase in the prescription rates of PP6M is expected and real-world efficacy and tolerability studies will be conducted.