Psychiatric Pharmacy Essentials: Long-acting Injectable Antipsychotics

Long-acting injectable (LAI) antipsychotics are unique medication formulations used in psychiatric pharmacy to help improve patient outcomes. They offer several benefits compared to oral therapy, including confirmed patient adherence, consistent drug delivery, predictable bioavailability, and prevention of antipsychotic overdose. LAIs are commonly used with the notion that they will decrease relapse rates by improving medication adherence; however, the data is limited. The following questions address the safety and efficacy of LAIs.

  • What antipsychotics are available as long-acting injections (LAIs), how are they dosed, and do they require oral overlap?1-3
  • How do the LAIs compare to one another?4-9
  • How do the LAI formulations of antipsychotics compare to oral formulations regarding efficacy, adherence, and relapse prevention?10-18
  • What is the role of LAIs in first-episode/early schizophrenia?19-20
  • How do patients and providers feel about LAI use?21-27
  • Are patients ever on both LAIs and oral formulations?28
  • What are the limitations to using the olanzapine LAI?29-30
  • Many LAIs are expensive; where can I find cost-effectiveness data?31-32
  • What are the most common medication errors associated with LAIs and potential management strategies?33
  • Where can I receive training on how to use LAIs?34
  • How do I manage missed doses of common LAIs?35

Reviewer 1: Trisha McHugh, PharmD
Reviewer 1: Austin Smith, PharmD, BCPP
2024-2025 AAPP Resident and New Practitioner Committee

  1. Pocket Guide to LAIs. In: Distributed as part of the Long-Acting Injectable Antipsychotics; updated in 2019: Changing the Landscape of LAI Utilization symposium offered at the 2014 AAPP Annual Meeting.. 2019.
  2. PRESKORN SH. Switching From the Oral to the Depot Formulation of a Medication: Clinically Relevant Pharmacokinetic Concepts and Considerations. Journal of Psychiatric Practice. 2017 May;23(3):200-209. Ovid Technologies (Wolters Kluwer Health). DOI: 10.1097/pra.0000000000000236.
  3. What should clinicians know about Invega Hafyera (paliperidone palmitate 6-month LAI)?. Available from: https://www.invegahafyerahcp.com/?utm_source=bing&utm_medium=cpc&utm_campaign=BI-USA-ENG-PS-InvegaHafyera-BC-PH-RN-HCP_Hafyera+Core&utm_content=Invega+Hafyera+-+Brand+Core&utm_term=hafyera&gclid=266d28bf0b5115e5a99b4e0c729fd39e&gclsrc=3p.ds&msclkid=266d28bf0b5115e5a99b4e0c729fd39e
  4. Schreiner A, Bergmans P, Cherubin P, Keim S, Llorca PM, Cosar B, et al. Paliperidone palmitate in non-acute patients with schizophrenia previously unsuccessfully treated with risperidone long-acting therapy or frequently used conventional depot antipsychotics. J Psychopharmacol. 2015 Aug;29(8):910-922. SAGE Publications. DOI: 10.1177/0269881115586284.
  5. Citrome L. New second-generation long-acting injectable antipsychotics for the treatment of schizophrenia. Expert Rev Neurother. 2013 Jul;13(7):767-783. Informa UK Limited. DOI: 10.1586/14737175.2013.811984.
  6. Clark I, Taylor D. Newer Formulations of Risperidone: Role in the Management of Psychotic Disorders. CNS Drugs. 2020 Aug;34(8):841-852. Springer Science and Business Media LLC. DOI: 10.1007/s40263-020-00735-3.
  7. Mathews M, Gopal S, Singh A, Nuamah I, Pungor K, Tan W, et al. <p>Comparison of Relapse Prevention with 3 Different Paliperidone Formulations in Patients with Schizophrenia Continuing versus Discontinuing Active Antipsychotic Treatment: A Post-Hoc Analysis of 3 Similarly Designed Randomized Studies</p>. NDT. 2020 Jun;Volume 16:1533-1542. Informa UK Limited. DOI: 10.2147/ndt.s221242.
  8. Jann MW, Penzak SR. Long-Acting Injectable Second-Generation Antipsychotics: An Update and Comparison Between Agents. CNS Drugs. 2018 Mar;32(3):241-257. Springer Science and Business Media LLC. DOI: 10.1007/s40263-018-0508-6.
  9. Ostuzzi G, Bertolini F, Del Giovane C, Tedeschi F, Bovo C, Gastaldon C, et al. Maintenance Treatment With Long-Acting Injectable Antipsychotics for People With Nonaffective Psychoses: A Network Meta-Analysis. AJP. 2021 May 1;178(5):424-436. American Psychiatric Association Publishing. DOI: 10.1176/appi.ajp.2020.20071120.
  10. Macfadden W, Bossie CA, Turkoz I, Haskins JT. Risperidone long-acting therapy in stable patients with recently diagnosed schizophrenia. Int Clin Psychopharmacol. 2010 Mar;25(2):75-82. Ovid Technologies (Wolters Kluwer Health). DOI: 10.1097/yic.0b013e3283347cbf.
  11. Schneider-Thoma J, Chalkou K, Dörries C, Bighelli I, Ceraso A, Huhn M, et al. Comparative efficacy and tolerability of 32 oral and long-acting injectable antipsychotics for the maintenance treatment of adults with schizophrenia: a systematic review and network meta-analysis. Lancet. 2022 Feb;399(10327):824-836. Elsevier BV. DOI: 10.1016/s0140-6736(21)01997-8.
  12. Gaebel W, Schreiner A, Bergmans P, de Arce R, Rouillon F, Cordes J, et al. Relapse Prevention in Schizophrenia and Schizoaffective Disorder with Risperidone Long-Acting Injectable vs Quetiapine: Results of a Long-Term, Open-Label, Randomized Clinical Trial. Neuropsychopharmacol. 2010 Nov;35(12):2367-2377. Springer Science and Business Media LLC. DOI: 10.1038/npp.2010.111.
  13. Zhu B, Ascher-Svanum H, Shi L, Faries D, Montgomery W, Marder SR. Time to Discontinuation of Depot and Oral First-Generation Antipsychotics in the Usual Care of Schizophrenia. PS. 2008 Mar;59(3):315-317. American Psychiatric Association Publishing. DOI: 10.1176/ps.2008.59.3.315.
  14. Shi L, Ascher-Svanum H, Zhu B, Faries D, Montgomery W, Marder SR. Characteristics and Use Patterns of Patients Taking First-Generation Depot Antipsychotics or Oral Antipsychotics for Schizophrenia. PS. 2007 Apr;58(4):482-488. American Psychiatric Association Publishing. DOI: 10.1176/ps.2007.58.4.482.
  15. Rosenheck RA, Krystal JH, Lew R, Barnett PG, Fiore L, Valley D, et al. Long-Acting Risperidone and Oral Antipsychotics in Unstable Schizophrenia. N Engl J Med. 2011 Mar 3;364(9):842-851. Massachusetts Medical Society. DOI: 10.1056/nejmoa1005987.
  16. Kishimoto T, Hagi K, Kurokawa S, Kane JM, Correll CU. 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 May;8(5):387-404. Elsevier BV. DOI: 10.1016/s2215-0366(21)00039-0.
  17. Buckley PF, Schooler NR, Goff DC, Kopelowicz A, Lauriello J, Manschreck TC, et al. Comparison of Injectable and Oral Antipsychotics in Relapse Rates in a Pragmatic 30-Month Schizophrenia Relapse Prevention Study. PS. 2016 Dec 1;67(12):1370-1372. American Psychiatric Association Publishing. DOI: 10.1176/appi.ps.201500466.
  18. Kirson NY, Weiden PJ, Yermakov S, Huang W, Samuelson T, Offord SJ, et al. Efficacy and Effectiveness of Depot Versus Oral Antipsychotics in Schizophrenia. J Clin Psychiatry. 2013 Jun 15;74(06):568-575. Physicians Postgraduate Press, Inc. DOI: 10.4088/jcp.12r08167.
  19. Lian L, Kim DD, Procyshyn RM, Fredrikson DH, Cázares D, Honer WG, et al. Efficacy of long‐acting injectable versus oral antipsychotic drugs in early psychosis: A systematic review and meta‐analysis. Early Intervention Psych. 2022 Jun;16(6):589-599. Wiley. DOI: 10.1111/eip.13202.
  20. Lian L, Kim DD, Procyshyn RM, Cázares D, Honer WG, Barr AM. Long-acting injectable antipsychotics for early psychosis: A comprehensive systematic review. PLoS ONE. 2022 Apr 29;17(4):e0267808. Public Library of Science (PLoS). DOI: 10.1371/journal.pone.0267808.
  21. West JC, Marcus SC, Wilk J, Countis LM, Regier DA, Olfson M. Use of Depot Antipsychotic Medications for Medication Nonadherence in Schizophrenia. Schizophrenia Bulletin. 2008 Jul 21;34(5):995-1001. Oxford University Press (OUP). DOI: 10.1093/schbul/sbm137.
  22. Patel M, Haddad P, Chaudhry I, McLoughlin S, David A. Psychiatrists’ use, knowledge and attitudes to first- and second-generation antipsychotic long-acting injections: comparisons over 5 years. J Psychopharmacol. 2010 Oct;24(10):1473-1482. SAGE Publications. DOI: 10.1177/0269881109104882.
  23. Patel M, de Zoysa N, Bernadt M, Bindman J, David A. Are depot antipsychotics more coercive than tablets?. J Psychopharmacol. 2010 Oct;24(10):1483-1489. SAGE Publications. DOI: 10.1177/0269881109103133.
  24. Iyer S, Banks N, Roy MA, Tibbo P, Williams R, Manchanda R, et al. A Qualitative Study of Experiences with and Perceptions regarding Long-Acting Injectable Antipsychotics: Part I—Patient Perspectives. Can J Psychiatry. 2013 May;58(5_suppl):14-22. SAGE Publications. DOI: 10.1177/088740341305805s03.
  25. Hand I. Gambling in Europe, part I: Germany. J Gambl Stud. 1992 Mar;8(1):3-9. Springer Science and Business Media LLC. DOI: 10.1007/bf01881465.
  26. Heres S, Schmitz FS, Leucht S, Pajonk FG. The attitude of patients towards antipsychotic depot treatment. Int Clin Psychopharmacol. 2007 Sep;22(5):275-282. Ovid Technologies (Wolters Kluwer Health). DOI: 10.1097/yic.0b013e3280c28424.
  27. Kirschner M, Theodoridou A, Fusar-Poli P, Kaiser S, Jäger M. Patients’ and clinicians’ attitude towards long-acting depot antipsychotics in subjects with a first episode of psychosis. Ther Adv Psychopharmacol. 2013 Apr;3(2):89-99. SAGE Publications. DOI: 10.1177/2045125312464106.
  28. Aggarwal NK, Sernyak MJ, Rosenheck RA. Prevalence of Concomitant Oral Antipsychotic Drug Use Among Patients Treated With Long-Acting, Intramuscular, Antipsychotic Medications. Journal of Clinical Psychopharmacology. 2012 Jun;32(3):323-328. Ovid Technologies (Wolters Kluwer Health). DOI: 10.1097/jcp.0b013e31825244f6.
  29. Detke HC, McDonnell DP, Brunner E, Zhao F, Sorsaburu S, Stefaniak VJ, et al. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases. BMC Psychiatry. 2010 Dec;10(1). Springer Science and Business Media LLC. DOI: 10.1186/1471-244x-10-43.
  30. McDonnell DP, Detke HC, Bergstrom RF, Kothare P, Johnson J, Stickelmeyer M, et al. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, II: investigations of mechanism. BMC Psychiatry. 2010 Dec;10(1). Springer Science and Business Media LLC. DOI: 10.1186/1471-244x-10-45.
  31. Lin J, Wong B, Offord S, Mirski D. Healthcare Cost Reductions Associated with the Use of LAI Formulations of Antipsychotic Medications Versus Oral Among Patients with Schizophrenia. J Behav Health Serv Res. 2013 Jul;40(3):355-366. Springer Science and Business Media LLC. DOI: 10.1007/s11414-013-9329-z.
  32. Joshi K, Muser E, Xu Y, Schwab P, Datar M, Suehs B. Adherence and economic impact of paliperidone palmitate versus oral atypical antipsychotics in a Medicare population. J Comp Eff Res. 2018 Aug;7(8):723-735. Becaris Publishing Limited. DOI: 10.2217/cer-2018-0003.
  33. Ross C, Adams KS, Crouse EL. Transitions of care: Assessment of adherence to long-acting injectable antipsychotic treatment following discharge from inpatient psychiatry. Mental Health Clinician. 2025 Feb;15(1):9-16. American Association of Psychiatric Pharmacists (AAPP). DOI: 10.9740/mhc.2025.02.009.
  34. Psychotropic Long-Acting Injectable (LAI) Training Program. In: AAPP [Internet]. Available from: /ed/lai
  35. Carpenter HJ. What We Can Do About It. Blackfriars. 1937 Aug;18(209):611-615. Cambridge University Press (CUP). DOI: 10.1111/j.1741-2005.1937.tb00096.x.