SpringerLink
Log in

Newer Formulations of Risperidone: Role in the Management of Psychotic Disorders

  • Review Article
  • Published:
CNS Drugs Aims and scope Submit manuscript

A Letter to the Editor to this article was published on 05 September 2020

Abstract

Antipsychotic long-acting injections improve relapse prevention in psychotic disorders. Three new risperidone formulations have been developed that offer advantages over currently available risperidone-based long-acting injections. Risperidone ISM® is a monthly intramuscular injection that does not require loading doses or concurrent oral risperidone. RBP-7000 is a monthly subcutaneous injection not requiring loading or oral supplementation. BB0817 is a 6-monthly implant of risperidone injected subcutaneously. All three preparations have been shown to be effective and well tolerated in clinical trials. A fourth formulation (TV-46000), which can be given subcutaneously every 1 or 2 months, has recently begun trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Castelao JF, Ferreira L, Gelders YG, Heylen SL. The efficacy of the D2 and 5-HT2 antagonist risperidone (R 64,766) in the treatment of chronic psychosis: an open dose-finding study. Schizophr Res. 1989;2(4–5):411–5.

    CAS  PubMed  Google Scholar 

  2. Borison RL, Pathiraja AP, Diamond BI, Meibach RC. Risperidone: clinical safety and efficacy in schizophrenia. Psychopharmacol Bull. 1992;28(2):213–8.

    CAS  PubMed  Google Scholar 

  3. Sachs GS, Grossman F, Ghaemi SN, Okamoto A, Bowden CL. Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety. Am J Psychiatry. 2002;159(7):1146–54.

    PubMed  Google Scholar 

  4. Nagaraj R, Singhi P, Malhi P. Risperidone in children with autism: randomized, placebo-controlled, double-blind study. J Child Neurol. 2006;21(6):450–5.

    PubMed  Google Scholar 

  5. Grant S, Fitton A. Risperidone: a review of its pharmacology and therapeutic potential in the treatment of schizophrenia. Drugs. 1994;48(2):253–73.

    CAS  PubMed  Google Scholar 

  6. Hogarty GE, Schooler NR, Ulrich R, Mussare F, Ferro P, Herron E. Fluphenazine and social therapy in the aftercare of schizophrenic patients: relapse analyses of a two-year controlled study of fluphenazine decanoate and fluphenazine hydrochloride. Arch Gen Psychiatry. 1979;36(12):1283–94.

    CAS  PubMed  Google Scholar 

  7. Kishimoto T, Robenzadeh A, Leucht C, et al. Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull. 2014;40(1):192–21313.

    PubMed  Google Scholar 

  8. Meyer JM. Understanding depot antipsychotics: an illustrated guide to kinetics. CNS Spectr. 2013;18(Suppl. 1):58–67.

    PubMed  Google Scholar 

  9. Taylor D. Establishing a dose-response relationship for haloperidol decanoate. Psychiatr Bull. 2005;29(3):104–7.

    Google Scholar 

  10. Bailey L, Taylor D. Estimating the optimal dose of flupentixol decanoate in the maintenance treatment of schizophrenia: a systematic review of the literature. Psychopharmacology. 2019;236(11):3081–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Ramstack M, Grandolfi GP, Mannaert E, D'Hoore P, Lasser RA. Long-acting risperidone: prolonged-release injectable delivery of risperidone using Medisorb®; microsphere technology. Schizophr Res. 2003;60(Suppl. 1):314.

    Google Scholar 

  12. Samtani MN, Vermeulen A, Stuyckens K. Population pharmacokinetics of intramuscular paliperidone palmitate in patients with schizophrenia: a novel once-monthly, long-acting formulation of an atypical antipsychotic. Clin Pharmacokinet. 2009;48(9):585–600.

    CAS  PubMed  Google Scholar 

  13. Knox ED, Stimmel GL. Clinical review of a long-acting, injectable formulation of risperidone. Clin Ther. 2004;26(12):1994–2002.

    CAS  PubMed  Google Scholar 

  14. Mauri MC, Paletta S, Di Pace C, Reggiori A, Cirnigliaro G, Valli I, Altamura AC. Clinical pharmacokinetics of atypical antipsychotics: an update. Clin Pharmacokinet. 2018;57:1493–528.

    CAS  PubMed  Google Scholar 

  15. Bossie CA, Sliwa JK, Ma YW, Fu DJ, Alphs L. Onset of efficacy and tolerability following the initiation dosing of long-acting paliperidone palmitate: post hoc analyses of a randomized, double-blind clinical trial. BMC Psychiatry. 2011;11:79.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Yapar E, İnal Ö, Özkan Y, Baykara T. Injectable in situ forming microparticles: a novel drug delivery system. Trop J Pharm Res. 2012;11(2):307–18.

    Google Scholar 

  17. Rungseevijitprapa W, Bodmeier R. Injectability of biodegradable in situ forming microparticle systems (ISM). Eur J Pharm Sci. 2009;36(4–5):524–31.

    CAS  PubMed  Google Scholar 

  18. Kranz H, Bodmeier R. Structure formation and characterization of injectable drug loaded biodegradable devices: in situ implants versus in situ microparticles. Eur J Pharm Sci. 2008;34(2–3):164–72.

    CAS  PubMed  Google Scholar 

  19. Kranz H, Brazeau GA, Napaporn J, Martin RL, Millard W, Bodmeier R. Myotoxicity studies of injectable biodegradable in-situ forming drug delivery systems. Int J Pharm. 2001;212(1):11–8.

    CAS  PubMed  Google Scholar 

  20. Kranz H, Yilmaz E, Brazeau GA, Bodmeier R. In vitro and in vivo drug release from a novel in situ forming drug delivery system. Pharm Res. 2008;25(6):1347–54.

    CAS  PubMed  Google Scholar 

  21. Carabias L, Llaudó J, Ayani I, Martínez-González J, Litman R, Gutierro I. A phase II study to evaluate the pharmacokinetics, safety, and tolerability of risperidone ISM multiple intramuscular injections once every 4 weeks in patients with schizophrenia. Int Clin Psychopharmacol. 2017;33(2):79–877.

    Google Scholar 

  22. Llaudo J, Anta L, Ayani I, et al. Phase I, open-label, randomized, parallel study to evaluate the pharmacokinetics, safety, and tolerability of one intramuscular injection of risperidone ISM at different dose strengths in patients with schizophrenia or schizoaffective disorder (PRISMA-1). Int Clin Psychopharmacol. 2016;31(6):323–31.

    PubMed  Google Scholar 

  23. Jain RA, Rhodes CT, Railkar AM, Malick AW, Shah NH. Controlled delivery of drugs from a novel injectable in situ formed biodegradable PLGA microsphere system. J Microencapsul. 2000;17(3):343–62.

    CAS  PubMed  Google Scholar 

  24. Farré MMJ, Cordero P, Martínez F, Ayani I, Fonseca F. A clinical trial to evaluate the pharmacokinetics, safety and tolerability of singledoses of risperidone with the novel long-acting injectable technology ISM inhealthy volunteers. Eur Arch Psychiatry Clin Neurosci. 2011;261:S57.

    Google Scholar 

  25. Samtani MN, Gopal S, Gassmann-Mayer C, Alphs L, Palumbo JM. Dosing and switching strategies for paliperidone palmitate: based on population pharmacokinetic modelling and clinical trial data. CNS Drugs. 2011;25(10):829–45.

    CAS  PubMed  Google Scholar 

  26. ClinicalTrials.gov. Study to evaluate the efficacy and safety of risperidone ISM® in patients with acute schizophrenia (PRISMA-3). https://clinicaltrials.gov/ct2/show/NCT03160521. Accessed Nov 2019.

  27. Pharmaceuticals ROVI. DORIA phase III trial hits primary endpoint March 2019. https://www.edisongroup.com/publication/doria-phase-iii-trial-hits-primary-endpoint/23705/. Accessed Nov 2019.

  28. ROVI. Completion of the PRISMA-3 and BORIS studies for Risperidone ISM®. 2019. https://www.rovi.es/sites/default/files/PR_Doria.pdf

  29. Citrome L. Sustained-release risperidone via subcutaneous injection: a systematic review of RBP-7000 (PERSERIS) for the treatment of schizophrenia. Clin Schizophr Relat Psychoses. 2018;12(3):130–41.

    PubMed  Google Scholar 

  30. Indivior. Perseris (risperidone) for extended-release injectable suspension, for subcutaneous use [prescribing information], revised July 2018. https://www.indivior.com/wp-content/uploads/2018/07/FDALabel-revised.pdf. Accessed 2 Aug 2018.

  31. Laffont CM, Gomeni R, Zheng B, Heidbreder C, Fudala PJ, Nasser AF. Population pharmacokinetics and prediction of dopamine D2 receptor occupancy after multiple doses of RBP-7000, a new sustained-release formulation of risperidone, in schizophrenia patients on stable oral risperidone treatment. Clin Pharmacokinet. 2014;53(6):533–43.

    CAS  PubMed  Google Scholar 

  32. Ivaturi V, Gopalakrishnan M, Gobburu JVS, et al. Exposure-response analysis after subcutaneous administration of RBP-7000, a once-a-month long-acting Atrigel formulation of risperidone. Br J Clin Pharmacol. 2017;83(7):1476–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Yarlagadda S. Atrigel drug delivery system: an approach for sustained effect. Pharm Reg Aff. 2012;1(4):248.

    Google Scholar 

  34. Karas A, Burdge G, Rey JA. Perseris™: a new and long-acting, atypical antipsychotic drug-delivery system. P T. 2019;44(8):460–6.

    PubMed  PubMed Central  Google Scholar 

  35. Gomeni R, Heidbreder C, Fudala PJ, Nasser AF. A model-based approach to characterize the population pharmacokinetics and the relationship between the pharmacokinetic and safety profiles of RBP-7000, a new, long-acting, sustained-released formulation of risperidone. J Clin Pharmacol. 2013;53(10):1010–9.

    CAS  PubMed  Google Scholar 

  36. Laffont CM, Gomeni R, Zheng B, Heidbreder C, Fudala PJ, Nasser AF. Population pharmacokinetic modeling and simulation to guide dose selection for RBP-7000, a new sustained-release formulation of risperidone. J Clin Pharmacol. 2015;55(1):93–103.

    CAS  PubMed  Google Scholar 

  37. Nasser AF, Henderson DC, Fava M, et al. Efficacy, safety, and tolerability of RBP-7000 once-monthly risperidone for the treatment of acute schizophrenia: an 8-week, randomized, double-blind, placebo-controlled, multicenter phase 3 study. J Clin Psychopharmacol. 2016;36(2):130–40.

    CAS  PubMed  Google Scholar 

  38. Isitt JJ, Nadipelli VR, Kouassi A, Fava M, Heidbreder C. Health-related quality of life in acute schizophrenia patients treated with RBP-7000 once monthly risperidone: an 8-week, randomized, double-blind, placebo-controlled, multicenter phase 3 study. Schizophr Res. 2016;174(1–3):126–31.

    PubMed  Google Scholar 

  39. Andorn A, Graham J, Csernansky J, et al. Monthly extended-release risperidone (RBP-7000) in the treatment of schizophrenia: results from the phase 3 program. J Clin Psychopharmacol. 2019;39(5):428–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Dhanda R, Varghese D, Nadipelli VR, et al. Patient-reported outcomes in schizophrenia patients treated with once-monthly extended-release risperidone in a long-term clinical study. Patient Prefer Adherence. 2019;13:1037–50.

    PubMed  PubMed Central  Google Scholar 

  41. Dammerman R, Kim S, Adera M, Schwarz A. Pharmacokinetics and safety of risperidone subcutaneous implants in stable patients with schizophrenia. Clin Pharmacol Drug Dev. 2018;7(3):298–310.

    CAS  PubMed  Google Scholar 

  42. BioSpace. Braeburn Pharmaceutical expands pipeline to include schizophrenia with Endo Pharmaceuticals deal. 1 May, 2015. https://www.biospace.com/article/releases/braeburn-pharmaceutical-expands-pipeline-to-include-schizophrenia-with-endo-pharmaceuticals-deal. Accessed 25 Apr 2020.

  43. Braeburn Pharmaceuticals. Braeburn Pharmaceuticals Achieves Primary Endpoint in Pivotal Phase 2/3 Study of BB0817, Risperidone 6-month Implant for Treatment of Schizophrenia. https://www.prnewswire.com/news-releases/braeburn-pharmaceuticals-achieves-primary-endpoint-in-pivotalphase-23-study-of-bb0817-risperidone-6-month-implant-for-treatment-of-schizophrenia-300446397.html. Accessed Apr 2020.

  44. ClinicalTrials.gov. Braeburn Pharmaceuticals. Safety and tolerability of risperidone implants. 6 December, 2018. https://clinicaltrials.gov/ct2/show/NCT02773576. Accessed 25 Apr 2020.

  45. AdisInsight. Risperidone controlled-release implant: Braeburn Pharmaceuticals. https://adisinsight.springer.com/drugs/800037596. Accessed Apr 2020.

  46. MedinCell. Building a global pharma leader; through long-acting injectables January 2019. https://invest.medincell.com/wp-content/uploads/2019/02/19-01-04-JPMprezvdef.pdf. Accessed 25 Apr 2020.

  47. MedinCell. https://www.medincell.com/bepo/. Accessed 10 Dec 2019.

  48. ClinicalTrials.gov. Evaluate TV-46000 as maintenance treatment in adult and adolescent patients with schizophrenia (RISE). https://clinicaltrials.gov/ct2/show/NCT03503318. Accessed Nov 2019.

  49. ClinicalTrials.gov. A study to test if TV-46000 is safe for maintenance treatment of schizophrenia. https://clinicaltrials.gov/ct2/show/NCT03893825. Accessed Dec 2019.

  50. Taylor D, Fischetti C, Sparshatt A, Thomas A, Bishara D, Cornelius V. Risperidone long-acting injection: a 6-year mirror-image study of healthcare resource use. Acta Psychiatr Scand. 2009;120(2):97–101.

    CAS  PubMed  Google Scholar 

  51. Taylor DM, Fischetti C, Sparshatt A, Thomas A, Bishara D, Cornelius V. Risperidone long-acting injection: a prospective 3-year analysis of its use in clinical practice. J Clin Psychiatry. 2009;70(2):196–200.

    CAS  PubMed  Google Scholar 

  52. Alphs L, Mao L, Lynn Starr H, Benson C. A pragmatic analysis comparing once-monthly paliperidone palmitate versus daily oral antipsychotic treatment in patients with schizophrenia. Schizophr Res. 2015;170:259–64.

    PubMed  Google Scholar 

  53. Taylor DM, Sparshatt A, O'Hagan M, Dzahini O. Effect of paliperidone palmitate on hospitalisation in a naturalistic cohort—a four-year mirror image study. Eur Psychiatry. 2016;37:43–8.

    CAS  PubMed  Google Scholar 

  54. Patel R, Chesney E, Taylor M, Taylor D, McGuire P. Is paliperidone palmitate more effective than other long-acting injectable antipsychotics? Psychol Med. 2018;48(10):1616–23.

    CAS  PubMed  Google Scholar 

  55. Lamb YN, Keating GM. Paliperidone palmitate intramuscular 3-monthly formulation: a review in schizophrenia. Drugs. 2016;76(16):1559–666.

    CAS  PubMed  Google Scholar 

  56. Samara MT, Leucht C, Leeflang MM, et al. Early improvement as a predictor of later response to antipsychotics in schizophrenia: a diagnostic test review. Am J Psychiatry. 2015;172(7):617–29.

    PubMed  Google Scholar 

  57. Kinon BJ, Chen L, Scher-Svanum H, et al. Predicting response to atypical antipsychotics based on early response in the treatment of schizophrenia. Schizophr Res. 2008;102(1–3):230–40.

    PubMed  Google Scholar 

  58. Taylor DM, Barnes TRE, Young AH. The Maudsley prescribing guidelines in psychiatry. 13th ed, vol 1. Chichester: Wiley; 2018. p. 82–5.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharmacy Department, Maudsley Hospital, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, UK

    Ivana Clark & David Taylor

Authors
  1. Ivana Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David Taylor.

Ethics declarations

Funding

David Taylor receives research funding from Janssen Pharmaceuticals and Lundbeck but no sources of funding were received for the preparation of this article.

Conflict of interest

Ivana Clark and David Taylor have no conflicts of interest that are directly relevant to the content of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Clark, I., Taylor, D. Newer Formulations of Risperidone: Role in the Management of Psychotic Disorders. CNS Drugs 34, 841–852 (2020). https://doi.org/10.1007/s40263-020-00735-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40263-020-00735-3

Search

Navigation