Clinical relevance of paliperidone palmitate 3-monthly in treating schizophrenia

Maju Mathews,1 Srihari Gopal,1 Isaac Nuamah,1 Ludger Hargarter,2 Adam J Savitz,1 Edward Kim,3 Wilson Tan,4 Bernardo Soares,5 Christoph U Correll6–81Department of Neuroscience, Janssen Research & Development, LLC, Raritan, NJ, USA; 2Department of Neuroscience, Janssen-Cilag EMEA, Neuss, Deutschland; 3Janssen Scientific Affairs, LLC, Hopewell, NJ, USA; 4Regional Medical Affairs, Janssen Pharmaceutical Companies of Johnson and Johnson, Singapore; 5Neuroscience Medical Affairs, Janssen-Cilag, High Wycombe, Buckinghamshire, UK; 6The Zucker Hillside Hospital, Psychiatry Research, Glen Oaks, NY, USA; 7Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, East Garden City, NY, USA; 8Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, GermanyAbstract: Antipsychotics are the mainstay in schizophrenia management, and long-acting injectable (LAI) antipsychotics contribute to the successful maintenance of treatment by improving non-adherence and preventing relapses. Paliperidone palmitate 3-monthly (PP3M) formulation is the only available LAI antipsychotic that offers an extended 3-month window of stable plasma drug concentration, enabling only four injections per year. This paper summarizes clinically relevant endpoints from available evidence for PP3M to bridge translational research gaps and provide measurable outcomes that can be interpreted in clinical practice. Low number-needed-to-treat (NNT) for relapse prevention (NNT [95% CI] 6-month estimate: 4.8 [3.2; 10.0]; 12-month estimate: 3.4 [2.2; 7.0]), and high number-needed-to-harm (NNH [95% CI] akathisia, 27.1 [12.3; −667.1]; tremor, 80.0 [22.5; 67.3]; dyskinesia, −132.6 [44.5; −23.2]; parkinsonism, 160.0 [28.9; −49.8]) quantify the relative benefits and low propensity for adverse events with PP3M. Symptom remission and reductions in positive and negative symptoms indicate treatment stability. Additionally, meaningful functional remission, reduced dosing frequency, and freedom from daily negotiations favorably impact patient preference and attenuate burdensome aspects of caregiving, representing important healthcare determinants that enhance prospects of treatment continuity in schizophrenia. This information can potentially improve clinicians’ judgment of treatment choices, clinical response, and patient selection in routine care. Taken together, PP3M is a valuable antipsychotic treatment option, meriting consideration for a broader role in the long-term management of schizophrenia; its utility should not be limited to patients with poor adherence or when oral antipsychotics have failed.Keywords: number-needed-to-harm, number-needed-to-treat, paliperidone palmitate 3-monthly, remissio