Long-acting injectable (LAI) antipsychotics are unique tools 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 improve medication adherence; however, data is limited regarding their ability to reduce relapse rates. The following questions will need to be answered to employ safe and effective use of LAIs. 

Essential Questions and References

What antipsychotics are available as long-acting injections (LAIs)? How are they dosed?  Do they require oral overlap? If so, for how long?

  1. 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).
  2. Nelson LA. Second Generation Antipsychotic Long-acting Injectables: Potential Benefits and Obstacles to Appropriate and Effective Utilization. Presented at the CPNP Annual Meeting (2016). [Weblink]
    • Presentation reviews benefits of utilizing long-acting injectables (LAI) antipsychotic medications, outlines the advantages of LAI over oral formulations in first episode psychosis, key factors to consider when selecting a second generation antipsychotic (SGA) LAI for an individual patient and barriers to using SGA LAI therapy and potential strategies to overcoming these barriers in clinical practice.
  3. Preskorn SH. 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.

How do the newer LAIs compare to one another?

  1. Schreiner A, Bergmans P, Cherubin P, Keim S, Llorca P-M, 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;29(8):910-22. DOI: 10.1177/0269881115586284. PubMed PMID: 25999398; PubMed Central PMCID: PMC4512527.
  2. Citrome L. New second-generation long-acting injectable antipsychotics for the treatment of schizophrenia. Expert Rev Neurother. 2013;13(7):767-83. DOI: 10.1586/14737175.2013.811984. PubMed PMID: 23898849.
  3. Clark I, Taylor D. Newer Formulations of Risperidone: Role in the Management of Psychotic Disorders. CNS Drugs. 13th ed. 2020;34(8):841-852. DOI: 10.1007/s40263-020-00735-3. PubMed PMID: 32462508.
  4. 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 Jun 19;16:1533-1542.
  5. Jann MW, Penzak SR. 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.

How do the LAI formulations of antipsychotics compare to their oral formulations regarding efficacy, adherence and relapse prevention?

  1. 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]
  2. Leucht C, Heres C, Kane J, et al. Oral versus depot antipsychotic drugs for schizophrenia – a critical systematic review and meta-analysis of randomised long-term trials. Schizo Res 2011; 127(1-3): 83-92.  [PubMed]
  3. 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]
  4. Weiden PJ, Schooler NR, Weedon JC, Elmouchtari A, Sunakawa A, Goldfinger SM. A randomized controlled trial of long-acting injectable risperidone vs continuation on oral atypical antipsychotics for first-episode schizophrenia patients: initial adherence outcome. J. Clin. Psychiatry. 2009;70(10):1397-406. DOI: 10.4088/JCP.09m05284yel. PubMed PMID: 19906343.
  5. 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]
  6. 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;58(4):482-8. DOI: 10.1176/ps.2007.58.4.482. PubMed PMID: 17412849.
  7. 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;364(9):842-51. DOI: 10.1056/NEJMoa1005987. PubMed PMID: 21366475.
  8. Kishimoto T, Hagi K, Nitta M, Leucht S, Olfson M, Kane JM, et al. Effectiveness of Long-Acting Injectable vs Oral Antipsychotics in Patients With Schizophrenia: A Meta-analysis of Prospective and Retrospective Cohort Studies. Schizophr Bull. 2018;44(3):603-619. DOI: 10.1093/schbul/sbx090. PubMed PMID: 29868849; PubMed Central PMCID: PMC5890463.
  9. 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;67(12):1370-1372. DOI: 10.1176/appi.ps.201500466. PubMed PMID: 27476806.

What roles do LAIs have in preventing medication nonadherence and relapse?

  1. Weiden P, Rapkin B, Zygmunt A, et al. Postdischarge medication compliance of inpatients converted from an oral to a depot neuroleptic regimen. Psychiatr           Serv 1995; 45 (10) : 1049-1054.  [Pubmed]
  2. Agid O, Foussias G, Remington G. Long-acting injectable antipsychotics in the treatment of schizophrenia: their role in relapse prevention. Expert Opin Pharmacother. 2010;11(14):2301-17. DOI: 10.1517/14656566.2010.499125. PubMed PMID: 20586707.
  3. 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;34(5):995-1001. DOI: 10.1093/schbul/sbm137. PubMed PMID: 18093962; PubMed Central PMCID: PMC2518642.
  4. Nasrallah HA Triple advantages of injectable long acting second generation antipsychotics: Relapse prevention, neuroprotection, and lower mortality. Schizophr Res. 2018 Mar 3. pii: S0920-9964(18)30053-7. [PubMed]

How do patients and providers feel about LAI use?

  1. 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]
  2. Heres S, Schmitz FS, Leucht S, Pajonk F-G. The attitude of patients towards antipsychotic depot treatment. Int Clin Psychopharmacol. 2007;22(5):275-82. DOI: 10.1097/YIC.0b013e3280c28424. PubMed PMID: 17690596.
  3. Kirschner M, Theodoridou A, Fusar-Poli P, Kaiser S, J├Ąger M. 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.

Are patients ever on both LAIs and oral formulations?

  1. Aggarwal NK, Sernyak MJ, Rosenheck RA. Prevalence of concomitant oral antipsychotic drug use among patients treated with long-acting, intramuscular, antipsychotic medications. J Clin Psychopharmacol. 2012;32(3):323-8. DOI: 10.1097/JCP.0b013e31825244f6. PubMed PMID: 22544006.

What are the limitations to using the olanzapine LAI?

  1. 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;10:43. DOI: 10.1186/1471-244X-10-43. PubMed PMID: 20537128; PubMed Central PMCID: PMC2895589.
  2. 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 Psychiatrybmc Psychiatry. 2010;10:45. DOI: 10.1186/1471-244X-10-45. PubMed PMID: 20537130; PubMed Central PMCID: PMC2895590.

Many LAIs are expensive, where can I find cost-effectiveness data?

  1. Oilvares J, Rodriguez-Martinez A, Buron J, et al. Cost-effectives analysis of switching antipsychotic medication to long-acting injectable risperidone in patients with schizophrenia: a 12- and 24-month follow-up from the e-STAR database in Spain. Appl Health Econ Health Policy 2008; 6(1): 41-53.  [Pubmed]
  2. Collins CM, Aebi ME, Levin JB, Tatsuoka C, Cassidy KA, Sajatovic M. Post-hoc analysis of two clinical trials examining Customized Adherence Enhancement plus long acting injectable antipsychotic (CAE-L) in high-risk individuals with serious mental illness. Schizophrenia Res. 2018;202:433-434. DOI: 10.1016/j.schres.2018.07.024. PubMed PMID: 30032936.
  3. 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;7(8):723-735. DOI: 10.2217/cer-2018-0003. PubMed PMID: 29722547.

What are the most common medication errors associated with LAIs and potential management strategies?

  1. 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.