Individualizing LAI selection based on clinical profile, tolerability, and real-world feasibility
The expanding landscape of long-acting injectable antipsychotics has introduced meaningful opportunities to individualize schizophrenia management beyond what oral therapy alone can offer.1 Selecting among available agents requires weighing pharmacologic properties, administration route, dosing interval, tolerability profile, and practical considerations that influence sustained engagement with treatment.1,2
Antipsychotic LAIs are available in both intramuscular and subcutaneous formulations, with dosing intervals ranging from biweekly to several months depending on the agent.2 While all approved options share the goal of maintaining therapeutic plasma concentrations without daily dosing, differences in delivery mechanism, injection site, needle size, and initiation requirements can meaningfully influence patient preference and clinical workflow.1,2 Some newer formulations do not require a loading dose or oral supplementation period at initiation, reducing early-phase complexity and facilitating more straightforward treatment starts.1,3
Tolerability considerations remain relevant to LAI selection and shared decision-making. Compared with oral antipsychotics, injectable formulations bypass first-pass hepatic metabolism, resulting in more stable plasma concentrations that may reduce peak-related adverse effects.4 Weight gain, extrapyramidal symptoms, somnolence, and prolactin elevation remain considerations across the LAI class and vary by agent.5,6 Discussing these profiles transparently with patients and caregivers supports informed decision-making and may improve long-term adherence.
Practical factors, including injection site preference, frequency of clinic visits, insurance authorization processes, and specialty pharmacy relationships, warrant early consideration. Framing LAI therapy as a proactive, patient-centered approach to disease management, rather than a response to treatment failure, positions these options more favorably in shared clinical conversations and can support earlier adoption across the disease course.
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[1] Kane JM, Agid O, Castle DJ, Citrome L, Fagiolini A, Kishimoto T, Larrauri CA, Leucht S, Rubio JM, Sajatovic M, Schooler N, Correll CU. The Use of Long-Acting Injectables for People with Schizophrenia: Consensus Panel Recommendations for Overcoming Barriers and Implementing Treatment. Neurol Ther. 2025 Dec;14(6):2551-2581. doi: 10.1007/s40120-025-00838-3. Epub 2025 Oct 7. PMID: 41057718; PMCID: PMC12623523.
[2] Velligan D, Salinas GD, Belcher E, Franzenburg KR, Suett M, Thompson S, Hansen RT 3rd. Preferences for Selecting and Initiating Long-Acting Injectable Antipsychotic Agents for the Treatment of Patients With Schizophrenia: Results From the US DECIDE Survey. Schizophr Bull Open. 2025 Jan 8;6(1):sgaf001. doi: 10.1093/schizbullopen/sgaf001. PMID: 40110565; PMCID: PMC11920864
[3] Risperidone SC 1-2 Month (UZEDY) Monograph Risperidone Extended-Release Injectable Suspension for Subcutaneous Use (UZEDY) National Drug Monograph November 2023 va Pharmacy Benefits Management Services, Medical Advisory Panel, and VISN Pharmacist Executives FDA Approval Information Description/Mechanism of Action 1 Clinical Evidence Summary Efficacy Considerations 2,3. Accessed February 20, 2026. https://www.va.gov/formularyadvisor/DOC_PDF/MON_Risperidone_UZEDY_Monograph_Nov_2023.pdf
[4] Correll CU, Kim E, Sliwa JK, Hamm W, Gopal S, Mathews M, Venkatasubramanian R, Saklad SR. Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview. CNS Drugs. 2021 Jan;35(1):39-59. doi: 10.1007/s40263-020-00779-5. Epub 2021 Jan 28. Erratum in: CNS Drugs. 2025 Jan;39(1):111-112. doi: 10.1007/s40263-024-01138-4. PMID: 33507525; PMCID: PMC7873121.
[5] Fagiolini A, Cuomo A, De Berardis D, Dell’Osso B, Pompili M, Serafini G. Differentiating aspects of oral and long-acting injectable antipsychotic drugs for tailoring the therapy of schizophrenia in clinical practice: a narrative review. Int Clin Psychopharmacol. 2025 Nov 1;40(6):e1-e13. doi: 10.1097/YIC.0000000000000578. Epub 2025 Jan 22. PMID: 39835836; PMCID: PMC12459147.
[6] Pillinger T, Howes OD, Correll CU, Leucht S, Huhn M, Schneider-Thoma J, Gaughran F, Jauhar S, McGuire PK, Taylor DM, Young AH, McCutcheon RA. Antidepressant and antipsychotic side-effects and personalised prescribing: a systematic review and digital tool development. Lancet Psychiatry. 2023 Nov;10(11):860-876. doi: 10.1016/S2215-0366(23)00262-6. Epub 2023 Sep 26. PMID: 37774723; PMCID: PMC10878984.
