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
Reviewer 1: Joseph M. Cusimano, PharmD, BCPP
Reviewer 2: Lindsey M. Anderson, PharmD, BCPP, BCPS
2022-2023 AAPP Resident and New Practitioner Committee
- Pocket Guide to LAIs. Distributed as part of the Long-Acting Injectable Antipsychotics; updated in 2019: Changing the Landscape of LAI Utilization symposium offered at the 2014 CPNP Annual Meeting. [Weblink]
- Provides guidance on dosing parameters; supplying, storing, and handling; injection techniques; and considerations for success.
- Switching From the Oral to the Depot Formulation of a Medication: Clinically Relevant Pharmacokinetic Concepts and Considerations. J Psychiatric Pract. 2017;23(3):200-209. DOI: 10.1097/PRA.0000000000000236. PubMed PMID: 28492458..
- American Psychiatric Association. SMI Adviser. What should clinicians know about Invega Hafyera (paliperidone palmitate 6-month LAI)? Available at: [Weblink]
- Provides details on Invega Hafyera, and additional information regarding each LAI is available through SMI Adviser at [Weblink]
- 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;29(8):910-22. DOI: 10.1177/0269881115586284. PubMed PMID: 25999398; PubMed Central PMCID: PMC4512527..
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- Clark C, Taylor D. Newer formulations of risperidone: role in the management of psychotic disorders. CNS Drugs. 2020 May 27. doi: 10.1007/s40263-020-00735-3. [PubMed]
- Mathews M, Gopal S, Singh A, et al. 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. Neuropsychiatr Dis Treat. 2020;16:1533-1542. [PubMed]
- Long-Acting Injectable Second-Generation Antipsychotics: An Update and Comparison Between Agents. CNS Drugs. 2018;32(3):241-257. DOI: 10.1007/s40263-018-0508-6. PubMed PMID: 29569082..
- Ostuzzi G Bertolini F, Giovane CD, et al. Maintenance treatment with long-acting injectable antipsychotics for people with nonaffective psychoses: a network meta-analysis. Am J Psychiatry. 2021;178(5):424-436. [PubMed]
- Macfadden W, Ma U, Thomas Haskins J, et al. A prospective study comparing the long-term effectiveness of injectable risperidone long-acting therapy and oral aripiprazole in patients with schizophrenia. Psychiatry (Edgmont). 2010;7(11):23-31. [PubMed]
- Schneider-Thoma J, Chalkou K, Dörries I, 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;399:824-36. [PubMed]
- Gaebel W, Schreiner A, Bergmans P, 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. Neuropsychopharmacology. 2010;35(12):2367-2377. [PubMed]
- Zhu, Ascher-Svanum, Shi, et al. Time to discontinuation of depot and oral first-generation antipsychotics in the usual care of schizophrenia. Psychiatr Serv. 2008;59(3):3:15-3:17. [PubMed]
- Shi L, Ascher-Svanum H, Zhu B, et al. Characteristics and use patterns of patients taking first-generation depot antipsychotics or oral antipsychotics for schizophrenia. Psychiatr Serv. 2007;58(4):482-488. [PubMed]
- Rosenheck R, Krystal J, Lew R, et al. Long-acting risperidone and oral antipsychotics in unstable schizophrenia. N Engl J Med. 2011; 364(9): 842-851. [PubMed]
- Kishimoto T, Hagi K, Kurokawa, 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]
- Comparison of Injectable and Oral Antipsychotics in Relapse Rates in a Pragmatic 30-Month Schizophrenia Relapse Prevention Study. PS. 2016;67(12):1370-1372. DOI: 10.1176/appi.ps.201500466. PubMed PMID: 27476806..
- Kirson NY, Weiden PJ, Yermakov S, et al. Efficacy and effectiveness of depot versus oral antipsychotics in schizophrenia: synthesizing results across different research designs. J Clin Psychiatry. 2013;74(6):568-75. [PubMed]
- Lian L, Kim DD, Procyshyn RM et al. Efficacy of long-acting injectable versus oral antipsychotic drugs in early psychosis: A systematic review and meta-analysis. Early Interv Psychiatry. 2022;16(6):589-99. [PubMed]
- Lian L, Kim DD, Procyshyn RM et al. Long-acting injectable antipsychotics for early psychosis: A comprehensive systematic review. PLoS One. 2022;17(4):e0267808. [PubMed]
- West J, Marcus S, Wilk J, et al. Use of depot antipsychotic medications for medication nonadherence in schizophrenia. Schizophr Bull. 2008;34(5):995-1001. [PubMed]
- Patel M, Haddad P, Chaudhry I, et al. Psychiatrists’ use, knowledge and attitudes to first-and-second generation antipsychotic long-acting injections: comparisons over 5 years. J Psychopharmacol. 2010;24(10):1473-1482. [PubMed]
- Patel M, de Zoysa N, Bernadt M, Bindman J, David AS. Are depot antipsychotics more coercive than tablets? The patient’s perspective. J Psychopharmacol. 2010;24(10):1483-9. [PubMed]
- Iyer S, Banks N, Roy M, et al. A qualitative study of experiences with and perceptions regarding long-acting injectable antipsychotics: Part I—patient perspectives. Can J Psychiatry. 2013;58(5 Suppl 1):14S-22S. [PubMed]
- Iver S, Banks N, Roy M, et al. A qualitative study of experiences with and perceptions regarding long-acting injectable antipsychotics: Part II—physician perspectives. Can J Psychiatry. 2013;58(5 Supple 1):23S-29S. [PubMed]
- Heres S, Schmitz F, Leucht S, et al. The attitude of patients toward antipsychotic depot treatment. Int Clin Psychopharmacol. 2007;22(5):275-282. [PubMed]
- Patients' and clinicians' attitude towards long-acting depot antipsychotics in subjects with a first episode of psychosis. Ther Adv Psychopharmacol. 2013;3(2):89-99. DOI: 10.1177/2045125312464106. PubMed PMID: 24167680; PubMed Central PMCID: PMC3805393..
- Aggarwal N, Sernyak M, Rosenheck R. Prevalence of concomitant oral antipsychotic drug use among patients treated with long-acting intramuscular antipsychotic medications. J Clin Psychopharmacol. 2012;32(3):323-328. [PubMed]
- Detke H, McDonnell D, Brunner E, et al. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases. BMC Psychiatry. 2010;10:43. [PubMed]
- McDonnell D, Detke H, Bergstom R, et al. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, II: investigations of mechanism. BMC Psychiatry. 2010;10:45. [PubMed]
- 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;40(3):355-66. [PubMed]
- Joshi K, Muser E, Xu Y, et al. Adherence and economic impact of paliperidone palmitate versus oral atypical antipsychotics in a Medicare population. J Comp Eff Res. 2018;7(8):723-735. [PubMed]
- Crouse EL. Long-acting injectable antipsychotics: what to do when things don’t go as planned. Presented at the CPNP Annual Meeting (2020). [Weblink]
- Presentation reviews recommended administration and monitoring for LAIs, highlighting specific areas that may be more prone to medication errors. The presentation also addresses treatment plans and modifications in response to LAI-related medication errors.