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Applied Health Economics and Health Policy

, Volume 11, Issue 2, pp 95–106 | Cite as

The Cost Effectiveness of Long-Acting/Extended-Release Antipsychotics for the Treatment of Schizophrenia

A Systematic Review of Economic Evaluations
  • Evanthia Achilla
  • Paul McCroneEmail author
Systematic Review

Abstract

Background

Antipsychotic medication is the mainstay of treatment in schizophrenia. Long-acting medication has potential advantages over daily medication in improving compliance and thus reducing hospitalization and relapse rates. The high acquisition and administration costs of such formulations raise the need for pharmacoeconomic evaluation.

Objective

The aim of this article is to provide a comprehensive review of the available evidence on the cost effectiveness of long-acting/extended-release antipsychotic medication and critically appraise the strength of evidence reported in the studies from a methodological viewpoint.

Methods

Relevant studies were identified by searching five electronic databases: PsycINFO, MEDLINE, EMBASE, the NHS Economic Evaluation Database and the Health Technology Assessment database (HTA). Search terms included, but were not limited to, ‘long-acting injection’, ‘economic evaluation’, ‘cost-effectiveness’ and ‘cost-utility’. No limits were applied for publication dates and language. Full economic evaluations on long-acting/extended-release antipsychotics were eligible for inclusion. Observational studies and clinical trials were also checked for cost-effectiveness information. Conference abstracts and poster presentations on the cost effectiveness of long-acting antipsychotics were excluded. Thirty-two percent of identified studies met the selection criteria. Pertinent abstracts were reviewed independently by two reviewers. Relevant studies underwent data extraction by one reviewer and were checked by a second, with any discrepancies being clarified during consensus meetings. Eligible studies were assessed for methodological quality using the quality checklist for economic studies recommended by the NICE guideline on interventions in the treatment and management of schizophrenia.

Results

After applying the selection criteria, the final sample consisted of 28 studies. The majority of studies demonstrated that risperidone long-acting injection, relative to oral or other long-acting injectable drugs, was associated with cost savings and additional clinical benefits and was the dominant strategy in terms of cost effectiveness. However, olanzapine in either oral or long-acting injectable formulation dominated risperidone long-acting injection in a Slovenian and a US study. Furthermore, in two UK studies, the use of long-acting risperidone increased the hospitalization days and overall healthcare costs, relative to other atypical or typical long-acting antipsychotics. Finally, paliperidone extended-release was the most cost-effective treatment compared with atypical oral or typical long-acting formulations. From a methodological viewpoint, most studies employed decision analytic models, presented results using average cost-effectiveness ratios and conducted comprehensive sensitivity analyses to test the robustness of the results.

Limitations

Variations in study methodologies restrict consistent and direct comparisons across countries. The exclusion of a large body of potentially relevant conference abstracts as well as some papers being unobtainable may have increased the likelihood of misrepresenting the overall cost effectiveness of long-acting antipsychotics. Finally, the review process was restricted to qualitative assessment rather than a quantitative synthesis of results, which could provide more robust conclusions.

Conclusions

Atypical long-acting (especially risperidone)/extended-release antipsychotic medication is likely to be a cost-effective, first-line strategy for managing schizophrenia, compared with long-acting haloperidol and other oral or depot formulations, irrespective of country-specific differences. However, inconsistencies in study methodologies and in the reporting of study findings suggest caution needs to be applied in interpreting these findings.

Keywords

Schizophrenia Risperidone Olanzapine Aripiprazole Oral Risperidone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors would like to thank Leonardo Koeser and Hiong Tie (both researchers at the Centre for the Economics of Mental and Physical Health, King’s College, London) for their assistance in translating foreign-language papers.

Author contributions

Evanthia Achilla took the lead on conducting the review and writing the paper. Both Evanthia Achilla and Paul McCrone independently screened abstracts. Paul McCrone contributed to the writing of the paper and acts as guarantor of the content.

Conflicts of interest

This systematic review received no external funding. The authors declare no conflicts of interest. Paul McCrone has received honorarium from Janssen and Lilly for speaking at meetings.

Supplementary material

40258_2013_16_MOESM1_ESM.pdf (85 kb)
Supplementary material 1 (PDF 84.6 kb)
40258_2013_16_MOESM2_ESM.pdf (106 kb)
Supplementary material 2 (PDF 105 kb)
40258_2013_16_MOESM3_ESM.pdf (145 kb)
Supplementary material 3 (PDF 144 kb)

References

  1. 1.
    World Health Organization (WHO). The global burden of disease: 2004 update. 2008 [online]. http://www.who.int/healthinfo/global_burden_disease/estimates_regional/en/index.html. Accessed 15 May 2012.
  2. 2.
    Saha S, Chant D, Welham J, et al. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005;2(5):e141.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    McGrath J, Saha S, Welham J, et al. A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology. BMC Med. 2004;2:13.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Knapp M, Mangalore R, Simon J. The global costs of schizophrenia. Schizophr Bull. 2004;30(2):279–93.PubMedCrossRefGoogle Scholar
  5. 5.
    American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2004;161(Suppl. 2):1–56.Google Scholar
  6. 6.
    Jones PB, Barnes TR, Davies L, et al. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry. 2006;63(10):1079–87.PubMedCrossRefGoogle Scholar
  7. 7.
    Leucht S, Wahlbeck K, Hamann J, et al. New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet. 2003;361(9369):1581–9.PubMedCrossRefGoogle Scholar
  8. 8.
    National Institute for Health and Clinical Excellence (NICE). National Clinical Guideline 82 on core interventions in the treatment and management of schizophrenia in adults in primary and secondary care [updated edition 2009]. http://publications.nice.org.uk/schizophrenia-cg82. Accessed 15 Apr 2012.
  9. 9.
    Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353(12):1209–23.PubMedCrossRefGoogle Scholar
  10. 10.
    Almond S, Knapp M, Francois C, et al. Relapse in schizophrenia: costs, clinical outcomes and quality of life. Br J Psychiatry. 2004;184:346–51.PubMedCrossRefGoogle Scholar
  11. 11.
    Joyce AT, Harrison DJ, Loebel AD, et al. Impact of atypical antipsychotics on outcomes of care in schizophrenia. Am J Manag Care. 2005;11(Suppl. 8):s254–61.PubMedGoogle Scholar
  12. 12.
    Heeg B, Buskens E, Botteman M, et al. The cost-effectiveness of atypicals in the UK. Value Health. 2008;11(7):1007–21.PubMedCrossRefGoogle Scholar
  13. 13.
    Moore DB, Kelly DL, Sherr JD, et al. Rehospitalization rates for depot antipsychotics and pharmacoeconomic implications: comparison with risperidone. Am J Health Syst Pharm. 1998;55(Suppl. 4):s17–9.PubMedGoogle Scholar
  14. 14.
    Haycox A. Pharmacoeconomics of long-acting risperidone: results and validity of cost-effectiveness models. Pharmacoeconomics. 2005;23(Suppl. 1):3–16.PubMedGoogle Scholar
  15. 15.
    Keith S. Use of long-acting risperidone in psychiatric disorders: focus on efficacy, safety and cost-effectiveness. Expert Rev Neurother. 2009;9(1):9–31.PubMedCrossRefGoogle Scholar
  16. 16.
    Fleischhacker WW, Eerdekens M, Karcher K, et al. Treatment of schizophrenia with long-acting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic. J Clin Psychiatry. 2003;64(10):1250–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Chue PS, Heeg B, Buskens E, et al. Modelling the impact of compliance on the costs and effects of long-acting risperidone in Canada. Pharmacoeconomics. 2005;23(Suppl. 1):62–74.PubMedGoogle Scholar
  18. 18.
    Oh PI, Lanctot KL, Mittmann N, et al. Cost-utility of risperidone compared with standard conventional antipsychotics in chronic schizophrenia. J Med Econ. 2001;4:137–56.CrossRefGoogle Scholar
  19. 19.
    Annemans L. Cost effectiveness of long-acting risperidone: what can pharmacoeconomic models teach us? Pharmacoeconomics. 2005;23(Suppl. 1):1–2.PubMedGoogle Scholar
  20. 20.
    Chue P. Long-acting risperidone injection: efficacy, safety, and cost-effectiveness of the first long-acting atypical antipsychotic. Neuropsychiatr Dis Treat. 2007;3(1):2007–39.CrossRefGoogle Scholar
  21. 21.
    Fleischhacker WW. Second-generation antipsychotic long-acting injections: systematic review. Br J Psychiatry. 2009;52:s29–36.CrossRefGoogle Scholar
  22. 22.
    Bartko G, Feher L. Pharmacoeconomic review of the use of injectable long-acting risperidone [Hungarian]. Neuropsychopharmacol Hung. 2005;7(4):199–207.PubMedGoogle Scholar
  23. 23.
    Bhanji NH, Chouinard G, Margolese HC. A review of compliance, depot intramuscular antipsychotics and the new long-acting injectable atypical antipsychotic risperidone in schizophrenia. Eur Neuropsychopharmacol. 2004;14(2):87–92.PubMedCrossRefGoogle Scholar
  24. 24.
    Curran MP, Keating GM. Management of schizophrenia: defining the role of long-acting injectable risperidone. Dis Manag Health Outcomes. 2006;14(2):107–25.CrossRefGoogle Scholar
  25. 25.
    Harrison TS, Goa KL. Spotlight on long-acting risperidone in schizophrenia. Am J Drug Deliv. 2004;2(3):L207–10.CrossRefGoogle Scholar
  26. 26.
    Love RC, Conley RJ. Long-acting risperidone injection. Am J Health Syst Pharm. 2004;61:1792–800.PubMedGoogle Scholar
  27. 27.
    Purgato M, Adams CE. Bromperidol decanoate (depot) for schizophrenia. Cochrane Database Syst Rev. 2011;9(1):54.Google Scholar
  28. 28.
    De Graeve D, Smet A, Mehnert A, et al. Long-acting risperidone compared with oral olanzapine and haloperidol depot in schizophrenia: a Belgian cost-effectiveness analysis. Pharmacoeconomics. 2005;23(Suppl. 1):35–47.PubMedGoogle Scholar
  29. 29.
    Hensen M, Heeg B, Lthgren M, et al. Cost effectiveness of long-acting risperidone in Sweden. Appl Health Econ Health Policy. 2010;8(5):327–41.PubMedCrossRefGoogle Scholar
  30. 30.
    Laux G, Heeg B, van Hout BA, et al. Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany. Pharmacoeconomics. 2005;23:49–61.PubMedCrossRefGoogle Scholar
  31. 31.
    Llorca PM, Miadi-Fargier H, Lancon C, et al. Cost-effectiveness analysis of schizophrenic patient care settings: impact of an atypical antipsychotic under long-acting injection formulation [French]. Encephale. 2005;31(2):235–46.PubMedCrossRefGoogle Scholar
  32. 32.
    Yang YK, Tarn YH, Wang TY, et al. Pharmacoeconomic evaluation of schizophrenia in Taiwan: model comparison of long-acting risperidone versus olanzapine versus depot haloperidol based on estimated costs. Psychiatry Clin Neurosci. 2005;59(4):385–94.PubMedCrossRefGoogle Scholar
  33. 33.
    Edwards NC, Rupnow MFT, Pashos CL, et al. Cost-effectiveness model of long-acting risperidone in schizophrenia in the US. Pharmacoeconomics. 2005;23(3):299–314.PubMedCrossRefGoogle Scholar
  34. 34.
    Edwards NC, Locklear JC, Rupnow MF, et al. Cost effectiveness of long-acting risperidone injection versus alternative antipsychotic agents in patients with schizophrenia in the USA. Pharmacoeconomics. 2005;23(Suppl. 1):75–89.PubMedGoogle Scholar
  35. 35.
    Yang L, Li M, Tao LB, et al. Cost-effectiveness of long-acting risperidone injection versus alternative atypical antipsychotic agents in patients with schizophrenia in China. Value Health. 2009;12(Suppl. 3):66–9.CrossRefGoogle Scholar
  36. 36.
    Heeg BM, Antunes J, Figueira ML, et al. Cost-effectiveness and budget impact of long-acting risperidone in Portugal: a modeling exercise. Curr Med Res Opin. 2008;24(2):349–58.PubMedCrossRefGoogle Scholar
  37. 37.
    Mantovani LG, Berto P, D’ Ausilio A, et al. Costs and effects of Long Acting Risperidone (LAR) versus atypical antipsychotics in the treatment of schizophrenic subjects in Italy. Farmeconomia e percorsi terapeutici 2004;5(1):5–11.Google Scholar
  38. 38.
    Obradovic M, Mrhar A, Kos M. Cost-effectiveness of antipsychotics for outpatients with chronic schizophrenia. Int J Clin Pract. 2007;61(12):1979–88.PubMedCrossRefGoogle Scholar
  39. 39.
    Baca E, Bobes J, Canas F, et al. Cost-effectiveness analysis of long-acting injectable risperidone v. olanzapine and v. fluphenazine decanoate in treating schizophrenia [Spanish]. Rev Esp Econ Salud 2005; 4(5):273–85.Google Scholar
  40. 40.
    Knapp M, Windmeijer F, Brown J, et al. Cost-utility analysis of treatment with olanzapine compared with other antipsychotic treatments in patients with schizophrenia in the pan-European SOHO study. Pharmacoeconomics. 2008;26(4):341–58.PubMedCrossRefGoogle Scholar
  41. 41.
    Furiak NM, Ascher-Svanum H, Klein RW, et al. Cost-effectiveness of olanzapine long-acting injection in the treatment of patients with schizophrenia in the United States: a micro-simulation economic decision model. Curr Med Res Opin. 2011;27(4):713–30.PubMedCrossRefGoogle Scholar
  42. 42.
    Edwards NC, Pesa J, Meletiche DM, et al. One-year clinical and economic consequences of oral atypical antipsychotics in the treatment of schizophrenia. Curr Med Res Opin. 2008;24(12):3341–55.PubMedCrossRefGoogle Scholar
  43. 43.
    Garcia-Ruiz AJ, Perez-Costillias L, Montesinos AC, et al. Cost-effectiveness analysis of antipsychotics in reducing schizophrenia relapses. Health Econ Rev. 2012;2(1):8.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Geitona M, Kousoulakou H, Ollandezos M, et al. Costs and effects of paliperidone extended release compared with alternative oral antipsychotic agents in patients with schizophrenia in Greece: a cost effectiveness study. Ann Gen Psychiatry. 2008;7(16):1–12.Google Scholar
  45. 45.
    Barnett PG, Scott JY, Rosenheck RA. How do clinical trial participants compare to other patients with schizophrenia? Schizophr Res. 2011;130:34–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Niaz OS, Haddad PM. Thirty-five months experience of risperidone long-acting injection in a UK psychiatric service including a mirror-image analysis of in-patient care. Act Psychiatr Scand. 2007;116:36–46.CrossRefGoogle Scholar
  47. 47.
    Carswell C, Wheeler A, Vanderpyl J, et al. Comparative effectiveness of long-acting risperidone: a report of resource utilisation and costs in a 12 month mirror-image analysis. Clin Drug Investig. 2010;30(11):777–87.PubMedCrossRefGoogle Scholar
  48. 48.
    Chang HC, Tang CH, Huang ST, McCrone P, Su KP. A cost-consequence analysis of long-acting injectable risperidone in schizophrenia: a one-year mirror-image study with national claim-based database in Taiwan. J Psychiatr Res. 2012;46(6):751–6.PubMedCrossRefGoogle Scholar
  49. 49.
    Spill B, Konoppa S, Kissling W, et al. Long-term observation of patients successfully switched to risperidone long-acting injectable: a retrospective, naturalistic 18-month mirror-image study of hospitalization rates and therapy costs. Int J Psychiatry Clin Pract. 2010;14(1):53–62.CrossRefGoogle Scholar
  50. 50.
    Young CL, Taylor DM. Health resource utilization associated with switching to risperidone long-acting injection. Act Psychiatr Scand. 2006;114(1):14–20.CrossRefGoogle Scholar
  51. 51.
    Olivares JM, Rodriguez-Martinez A, Buron JA, et al. Cost-effectiveness 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.PubMedCrossRefGoogle Scholar
  52. 52.
    Taylor D, Fischetti C, Sparshatt A, et al. Risperidone long-acting injection: a 6-year mirror-image study of healthcare resource use. Act Psychiatr Scanda. 2009;120(2):97–101.CrossRefGoogle Scholar
  53. 53.
    Knapp M. Costs of schizophrenia. Br J Psychiatry. 1997;171:509–18.PubMedCrossRefGoogle Scholar
  54. 54.
    Leal A, Rosillon D, Mehnert A, et al. Healthcare resource utilization during 1-year treatment with long-acting, injectable risperidone. Pharmacoepidemiol Drug Saf. 2004;13(11):811–6.PubMedCrossRefGoogle Scholar
  55. 55.
    Olivares JM, Peuskens J, Pecenak J, et al. Clinical and resource-use outcomes of risperidone long-acting injection in recent and long-term diagnosed schizophrenia patients: results from a multinational electronic registry. Curr Med Res Opin. 2009;25(9):2197–206.PubMedCrossRefGoogle Scholar
  56. 56.
    McEvoy JP. Risks versus benefits of different types of long-acting injectable antipsychotics. J Clin Psychiatry. 2006;67(Suppl. 5):15–8.PubMedGoogle Scholar
  57. 57.
    Ginnelly L, Manca A. The use of decision models in mental health economic evaluation: challenges and opportunities. Appl Health Econ Health Policy. 2003;2(3):157–64.PubMedGoogle Scholar
  58. 58.
    Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. PLoS Med. 2009;6(7):1–28.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  1. 1.Centre for Economics of Mental and Physical Health, Health Service and Population Research DepartmentPO24 Institute of Psychiatry, King’s College LondonLondonUK

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