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Original Research March 2, 2026

Outcomes and Practice Patterns of Long-Acting Injectable Versus Oral Antipsychotics Among Patients With Bipolar I Disorder in the United States: A Hospital Database Analysis

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J Clin Psychiatry 2026;87(2):25m16154

Abstract

Objective: To compare rehospitalization outcomes and medication practice patterns between long-acting injectable antipsychotics (LAIs) and oral antipsychotics (OAs) in US patients with bipolar I disorder (BD-I).

Methods: This retrospective cohort study using the Premier Hospital database (October 2020–September 2023) grouped adults (aged ≥18 years) hospitalized with BD-I by discharge medication: OA, LAI, or second-generation LAI (SG LAI). LAI and SG LAI patients were propensity score matched (1:4) to OA patients. Rehospitalization rates and risk (BD-I–related and all-cause) within 30, 60, and 90 days were assessed. Medication continuation vs switching at rehospitalization was also analyzed.

Results: Among 98,088 eligible patients, 78.1% were in the OA and 2.4% in the LAI group. BD-I–related rehospitalization rates were lower for LAI users at 30 (3.9% vs 5.0%, P=.033) and 60 days (5.9% vs 7.2%, P=.030) vs OAs. SG LAI users showed reductions in rehospitalizations at 30 (3.6% vs 5.4%; P=.010), 60 (5.2% vs 7.5%; P=.008), and 90 (6.8% vs 9.1%; P=.015) days. Risk of first BD-I rehospitalization within 30–90 days was reduced for LAI (hazard ratio [HR]: 0.784–0.856) and SG LAI (HR: 0.653–0.742) groups vs OAs.

Conclusions: LAIs, especially SG formulations, are associated with reduced rehospitalization in BD-I compared to OAs, supporting their broader use to improve adherence and reduce readmissions.

J Clin Psychiatry 2026;87(2):25m16154

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  1. Bobo WV. The diagnosis and management of bipolar I and II disorders: clinical practice update. Mayo Clin Proc. 2017;92(10):1532–1551. PubMed CrossRef
  2. Carvalho AF, Firth J, Vieta E. Bipolar disorder. N Engl J Med. 2020;383(1):58–66. PubMed CrossRef
  3. GBD 2019 Mental Disorders Collaborators. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry. 2022;9(2):137–150. PubMed CrossRef
  4. Merikangas KR, Jin R, He JP, et al. Prevalence and correlates of bipolar spectrum disorder in the World Mental Health Survey Initiative. Arch Gen Psychiatry. 2011;68(3):241–251. PubMed CrossRef
  5. Yan T, Greene M, Chang E, et al. Hospitalization risk factors in antipsychotic-treated schizophrenia, bipolar I disorder or major depressive disorder. J Comp Eff Res. 2019;8(4):217–227. PubMed CrossRef
  6. Peters AT, West AE, Eisner L, et al. The burden of repeated mood episodes in bipolar I disorder: results from the National Epidemiological Survey on Alcohol and Related Conditions. J Nerv Ment Dis. 2016;204(2):87–94. PubMed CrossRef
  7. Tohen M, Goldberg JF, Hassoun Y, et al. Identifying profiles of patients with bipolar I disorder who would benefit from maintenance therapy with a long-acting injectable antipsychotic. J Clin Psychiatry. 2020;81(4):OT19046AH1. PubMed CrossRef
  8. Oliva V, Fico G, De Prisco M, et al. Bipolar disorders: an update on critical aspects. Lancet Reg Health Eur. 2025;48:101135. PubMed CrossRef
  9. Dickson MC, Nguyen MM, Patel C, et al. Adherence, persistence, readmissions, and costs in Medicaid members with schizophrenia or schizoaffective disorder initiating paliperidone palmitate versus switching oral antipsychotics: a real-world retrospective investigation. Adv Ther. 2023;40(1):349–366. PubMed CrossRef
  10. Patel C, Emond B, Lafeuille MH, et al. Real-world analysis of switching patients with schizophrenia from oral risperidone or oral paliperidone to once-monthly paliperidone palmitate. Drugs Real World Outcomes. 2020;7(1):19–29. PubMed CrossRef
  11. Rubio JM, Taipale H, Tanskanen A, et al. Long-term continuity of antipsychotic treatment for schizophrenia: a nationwide study. Schizophr Bull. 2021;47(6):1611–1620. PubMed CrossRef
  12. Kane JM, Rubio JM, Casciano J, et al. Real-world outcomes and practice patterns among patients with schizophrenia when switched from oral antipsychotics to long-acting injectable formulations after hospitalization. Psychiatry Res. 2025;348:116455. PubMed CrossRef
  13. Kane JM, Schooler NR, Marcy P, et al. Effect of long-acting injectable antipsychotics vs usual care on time to first hospitalization in early-phase schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2020;77(12):1217–1224. PubMed CrossRef
  14. Kishimoto T, Hagi K, Kurokawa S, et al. Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort, and pre-post studies. Lancet Psychiatry. 2021;8(5):387–404. PubMed CrossRef
  15. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382(9896):951–962. PubMed CrossRef
  16. Maestri TJ, Mican LM, Rozea H, et al. Do long-acting injectable antipsychotics prevent or delay hospital readmission?. Psychopharmacol Bull. 2018;48(3):8–15. PubMed CrossRef
  17. Abilify Maintena. Product monograph. Otsuka Pharmaceutical Co., Ltd.; 2021.
  18. Risperdal Consta. Package insert. Janssen Pharmaceutical Companies; 2021.
  19. Vieta E, Tohen M, McIntosh D, et al. Early use of long-acting injectable antipsychotics in bipolar disorder type I: an expert consensus. Bipolar Disord. 2025;27(1):7–16. PubMed CrossRef
  20. Llorca PM, Abbar M, Courtet P, et al. Guidelines for the use and management of long-acting injectable antipsychotics in serious mental illness. BMC Psychiatry. 2013;13:340. PubMed CrossRef
  21. Correll CU, Citrome L, Haddad PM, et al. The use of long-acting injectable antipsychotics in schizophrenia: evaluating the evidence. J Clin Psychiatry. 2016;77(suppl 3):1–24. PubMed CrossRef
  22. Sajatovic M, Ross R, Legacy SN, et al. Initiating/maintaining long-acting injectable antipsychotics in schizophrenia/schizoaffective or bipolar disorder - expert consensus survey part 2. Neuropsychiatr Dis Treat. 2018;14:1475–1492. PubMed CrossRef
  23. Sajatovic M, Ross R, Legacy SN, et al. Identifying patients and clinical scenarios for use of long-acting injectable antipsychotics - expert consensus survey part 1. Neuropsychiatr Dis Treat. 2018;14:1463–1474. PubMed CrossRef
  24. Patel R, Liman C, Oyesanya M, et al. Retrospective cohort study of long-acting injectable (LAI) antipsychotic initiation in the inpatient setting: impact of LAI characteristics on transition and continuation of care among patients with schizophrenia in the USA. BMJ Open. 2025;15(3):e092216. PubMed CrossRef
  25. Jackson JW, Fulchino L, Rogers J, et al. Impact of drug-reimbursement policies on prescribing: a case-study of a newly marketed long-acting injectable antipsychotic among relapsed schizophrenia patients. Pharmacoepidemiol Drug Saf. 2018;27(1):95–104. PubMed CrossRef
  26. Fu AZ, Pesa JA, Lakey S, et al. Healthcare resource utilization and costs before and after long-acting injectable antipsychotic initiation in commercially insured young adults with schizophrenia. BMC Psychiatry. 2022;22(1):250. PubMed CrossRef
  27. Lohman MC, Scott V, Verma M, et al. Distribution and correlates of long-acting injectable antipsychotic use among community mental health center patients. Psychiatry Res. 2025;345:116378. PubMed CrossRef
  28. Greene M, Yan T, Chang E, et al. Medication adherence and discontinuation of long-acting injectable versus oral antipsychotics in patients with schizophrenia or bipolar disorder. J Med Econ. 2018;21(2):127–134. PubMed CrossRef
  29. Bessonova L, Ogden K, Doane MJ, et al. The economic burden of bipolar disorder in the United States: a systematic literature review. Clinicoecon Outcomes Res. 2020;12:481–497. PubMed CrossRef
  30. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–383. PubMed CrossRef
  31. Dembek C, Mackie D, Modi K, et al. The economic and humanistic burden of bipolar disorder in adults in the United States. Ann Gen Psychiatry. 2023;22(1):13. PubMed CrossRef
  32. Prajapati AR, Wilson J, Song F, et al. Second-generation antipsychotic long-acting injections in bipolar disorder: systematic review and meta-analysis. Bipolar Disord. 2018;20(8):687–696. PubMed CrossRef
  33. Gentile S. Discontinuation rates during long-term, second-generation antipsychotic long-acting injection treatment: a systematic review. Psychiatry Clin Neurosci. 2019;73(5):216–230. PubMed CrossRef
  34. Korkmaz SA, Gurler S. Real-world effectiveness of long-acting injectable vs. oral antipsychotics in patients with bipolar I disorder: a 1-year retrospective observational study. Curr Med Res Opin. 2024;40(5):855–861. PubMed CrossRef
  35. Kane JM, Mychaskiw MA, Lim S, et al. Treatment journey from diagnosis to the successful implementation of a long-acting injectable antipsychotic agent in young adults with schizophrenia. J Clin Psychiatry. 2023;84(3):22m14544. PubMed CrossRef

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