CNS Drugs

, Volume 27, Issue 1, pp 67–80 | Cite as

Lurasidone

In the Treatment of Schizophrenia
Adis Drug Profile

Abstract

This review focuses on the efficacy and tolerability of lurasidone, which is approved in the USA, Puerto Rico and Canada for the treatment of schizophrenia. In two placebo-controlled, phase II trials, lurasidone 40–120 mg/day was efficacious in reducing the acute symptoms of schizophrenia. In a third phase II trial, the lurasidone groups and haloperidol control group failed to separate from placebo on key endpoints. In two placebo- and active treatment-controlled, phase III trials, lurasidone at dosages of 40–160 mg/day, olanzapine 15 mg/day and quetiapine extended-release (XR) 600 mg/day were efficacious in reducing the symptoms of schizophrenia. In a 12-month, double-blind extension trial, the relapse rate in lurasidone recipients was noninferior to that in quetiapine XR recipients. In a third phase III trial, lurasidone 80 mg/day, but not 40 or 120 mg/day, was more efficacious than placebo for the primary endpoint. In an unpublished trial, there were no significant differences between lurasidone, active comparator and placebo groups on the primary endpoint. Lurasidone was generally well tolerated over the short and longer term. Extrapyramidal symptoms and akathisia occurred in ≈10–13 % of patients. Lurasidone was associated with a low risk of QT interval prolongation, weight gain, metabolic disturbances and hyperprolactinaemia. Further trials against other antipsychotics are needed to fully evaluate its efficacy and tolerability.

Notes

Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

References

  1. 1.
    van Os J, Kapur S. Schizophrenia. Lancet. 2009;374(9690):635–45.PubMedCrossRefGoogle Scholar
  2. 2.
    Kane JM, Correll CU. Past and present progress in the pharmacological treatment of schizophrenia. J Clin Psychiatry. 2010;71(9):1115–24.PubMedCrossRefGoogle Scholar
  3. 3.
    Jindal RD, Keshavan MS. Classifying antipsychotic agents: need for new terminology. CNS Drugs. 2008;22(12):1047–59.PubMedCrossRefGoogle Scholar
  4. 4.
    Hopkins CR. ACS chemical neuroscience molecule spotlight on Latuda (lurasidone; SM-13,496). ACS Chem Neurosci. 2011;2(2):58–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Sunovion Pharmaceuticals Inc. Latuda (lurasidone hydrochloride) tablets, for oral use: US prescribing information. 2012. http://latuda.com/LatudaPrescribingInformation.pdf. Accessed 2012 Sep 12.
  6. 6.
    Ishibashi T, Horisawa T, Tokuda K, et al. Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity. J Pharmacol Exp Ther. 2010;334(1):171–81.PubMedCrossRefGoogle Scholar
  7. 7.
    Fumagalli F, Calabrese F, Luoni A, et al. Modulation of BDNF expression by repeated treatment with the novel antipsychotic lurasidone under basal condition and in response to acute stress. Int J Neuropsychopharmcol. 2012;15(2):235–46.CrossRefGoogle Scholar
  8. 8.
    Yuen EY, Li X, Wei J, et al. The novel antipsychotic drug lurasidone enhances N-methyl-d-aspartate receptor-mediated synaptic responses. Mol Pharmacol. 2012;81(2):113–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Enomoto T, Ishibashi T, Tokuda K, et al. Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats. Behav Brain Res. 2008;186(2):197–207.PubMedCrossRefGoogle Scholar
  10. 10.
    Enomoto T. Effects of the novel antipsychotic lurasidone on prefrontal cognitive functioning in rats [abstract no. 646.24/V36]. 39th Annual Meeting of the Society for Neuroscience, Chicago, IL; 2009.Google Scholar
  11. 11.
    Ikeda K, Fukuoka T, Ikejiri M, et al. Cognitive enhancing effects of lurasidone in non-human primates: object retrieval with detours, a test of executive function [abstract]. Int J Neuropsychopharmcol. 2010;13:94–5.Google Scholar
  12. 12.
    Horiguchi M, Hannaway KE, Adelekun AE, et al. Subchronic treatment with lurasidone has both preventive and enduring reversal effects on the phencyclidine (PCP)-induced deficit in novel object recognition (NOR) in rats [abstract]. Neuropsychopharmacology. 2011;36:S436.Google Scholar
  13. 13.
    Potkin SG, Keator DB, Preda A, et al. D2 receptor occupancy measured with 18F-fallypride following lurasidone treatment in schizophrenia patients [abstract]. Neuropsychopharmacology. 2011;36:S173.Google Scholar
  14. 14.
    Harvey PD, Murasaki M, Cucchiaro J, et al. A three arm dose finding study of lurasidone: efficacy and tolerability data [abstract]. Schizophr Res. 2010;117(2–3):374–5.CrossRefGoogle Scholar
  15. 15.
    Chiu Y, Gu K, Poola N, et al. Effect of hepatic impairment on the pharmacokinetics of lurasidone [abstract]. Clin Pharmacol Ther. 2011;89:S32.Google Scholar
  16. 16.
    Preskorn S, Chiu YY, Sarubbi D, et al. Lurasidone pharmacokinetics: assessment of potential for drug-drug interactions [abstract]. Neuropsychopharmacology. 2010;35:S395.Google Scholar
  17. 17.
    Ogasa M, Kimura T, Nakamura M, et al. Lurasidone in the treatment of schizophrenia: a 6-week placebo-controlled study. Psychopharmacology (Berl). 2012 February 19 (Epub).Google Scholar
  18. 18.
    Centre for Drug Evaluation and Research. Medical review lurasidone 2010. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/200603Orig1s000MedR.pdf. Accessed 2012 Sep 12.
  19. 19.
    Nakamura M, Ogasa M, Guarino J, et al. Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-controlled trial. J Clin Psychiatry. 2009;70(6):829–36.PubMedCrossRefGoogle Scholar
  20. 20.
    Meltzer HY, Cucchiaro J, Silva R, et al. Lurasidone in the treatment of schizophrenia: a randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry. 2011;168(9):957–67.PubMedCrossRefGoogle Scholar
  21. 21.
    Loebel A, Cucchiaro J, Pikalov A, et al. Lurasidone in the treatment of acute schizophrenia: results of the double-blind, placebo-controlled, 6-week, pearl 3 trial [abstract]. Neuropsychopharmacology. 2010;35:S313–4.Google Scholar
  22. 22.
    Dainippon Sumitomo Pharma Co Ltd. Dainippon Sumitomo Pharma announces Pan-Asia study results for lurasidone, an atypical antipsychotic agent, in the treatment of schizophrenia [media release]. 2011. http://www.ds-pharma.com.
  23. 23.
    Pikalov A, Cucchiaro J, Sarma K, et al. Lurasidone in the acute treatment of schizophrenia: results of the double-blind placebo- and quetiapine XR-controlled 6-week study of lurasidone in adult patients with schizophrenia [abstract no. 225]. Poster presented at the 26th Annual US Psychiatric and Mental Health Congress. 2011 Nov 7-10, Las Vegas, NEV.Google Scholar
  24. 24.
    Stahl S, Cucchiaro J, Simonelli D, et al. Long-term safety and tolerability of lurasidone in subjects with schizophrenia: results of a 6-month, open-label study [abstract]. Neuropsychopharmacology. 2010;35:S316–7.CrossRefGoogle Scholar
  25. 25.
    Loebel A, Cucchiaro J, Xu J, et al. Relapse prevention with lurasidone vs. quetiapine XR in chronic schizophrenia: results of a 12-month, double-blind study. Neuropsychopharmacology. 2011;36:S101.Google Scholar
  26. 26.
    Harvey PD, Ogasa M, Cucchiaro J, et al. Performance and interview-based assessments of cognitive change in a randomized, double-blind comparison of lurasidone vs. ziprasidone. Schizophr Res. 2011;127(1–3):188–94.PubMedCrossRefGoogle Scholar
  27. 27.
    Citrome L. Lurasidone for the acute treatment of adults with schizophrenia: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? Clin Schizophr Relat Psychoses. 2012;6(2):76–85.PubMedCrossRefGoogle Scholar
  28. 28.
    Harvey P, Cucchiaro J, Pikalov A, et al. Cognitive performance in patients with schizophrenia treated with lurasidone: results from a placebo- and active-controlled acute phase study followed by a 6 month double-blind extension [abstract]. Neuropsychopharmacology. 2011;36:S169–70.CrossRefGoogle Scholar
  29. 29.
    Newcomer JW, Siu C, Pikalov A, et al. Impact of lurasidone and olanzapine on framingham 10-year coronary heart disease risk estimate in schizophrenia [abstract]. Schizophr Bull. 2011;37:316.CrossRefGoogle Scholar
  30. 30.
    Citrome L, Cucchiaro J, Sarma K, et al. Long-term safety and tolerability of lurasidone in schizophrenia: a 12-month, double-blind, active-controlled study. Int Clin Psychopharmacol. 2012;27(3):165–76.PubMedCrossRefGoogle Scholar
  31. 31.
    Sunovien. PEARL Schizophrenia Maintenance study (NCT01435928) [online]. http://clinicaltrials.gov/ct2/show/NCT01435928. Accessed Oct 9 2012.

Copyright information

© Springer International Publishing Switzerland 2012

Authors and Affiliations

  1. 1.AucklandNew Zealand

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