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Ruth Milz,1 Carmela Benson,1 Karl Knight,1 Jose Antunes,2 Dean Najarian,3 Paola-Maria Lopez Rengel,4 Steven Wang,1 Ute Richarz,5 Srihari Gopal,1 John M Kane6,7 1Janssen Research & Development LLC, Titusville, NJ, USA; 2Janssen-Cilag, Porto Salvo, Portugal; 3Janssen Scientific Affairs, LLC, Raritan, NJ, USA; 4Janssen Cilag, Madrid, Spain; 5Janssen Global Medical Affairs, Cilag, Zug, Switzerland; 6Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Queens, NY, USA; 7Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY, USACorrespondence: Ruth Milz, Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA, Email rmilz@ITS.JNJ.comAbstract: Medication nonadherence in schizophrenia can have serious implications including relapses and hospitalization. Long-acting injectable (LAI) antipsychotics require fewer administrations, while ensuring sustained medication coverage. In this review, we summarize the expected real-world benefits of longer dosing intervals in the management of schizophrenia. LAIs are associated with improved clinical outcomes of less frequent relapses and reduced functional impairment, encouraging patients to regain control of their lives. Aripiprazole lauroxil and paliperidone palmitate three-monthly (PP3M) LAIs have longer dosing intervals of 2– 3 months and provide improved outcomes in patients with schizophrenia. Paliperidone palmitate six-monthly (PP6M) LAI provides the longest dosing interval, twice-yearly dosing, among existing LAIs. Decreasing the frequency of LAI administrations has the potential to reduce occurrence of serious outcomes associated with poor medication adherence. By eliminating the need for daily oral antipsychotic dosing, LAIs could increase the likelihood of patient acceptance, decrease stigma, and promote self-esteem. Longer intervals of medication coverage may be desirable for patients with higher risk of relapse including adults with recent-onset schizophrenia, those living in circumstances that may deprive them of regular access (eg, homeless), those that are in transitions between care settings or to reduce interpersonal contact during public health emergencies (eg, COVID-19 pandemic).Keywords: adherence, long-acting injectable, paliperidone palmitate, schizophrenia