Clinical Drug Investigation

, Volume 33, Issue 12, pp 867–876 | Cite as

Paliperidone Extended-Release: Safety and Tolerability from a Metabolic Profile Perspective

  • Alfonso Rodríguez-Martínez
  • Carlos Guzmán Quilo
Review Article

Abstract

Pharmacologic management strategies for schizophrenia, a relatively common psychotic disorder, include the use of typical and atypical antipsychotic drugs. In general, typical (or conventional) antipsychotics have a proven track record in effectively managing the positive symptoms of schizophrenia but sometimes lack efficacy in treating negative symptoms. The conventional agents are also associated with adverse neurologic effects such as extrapyramidal symptoms (EPS). The development of atypical antipsychotics has partly ameliorated the issue of EPS induced by typical antipsychotics. However, several of these atypical antipsychotic agents have been associated with adverse metabolic effects, including weight gain, dyslipidemia, and increased serum glucose levels. Paliperidone (9-hydroxy-riperidone) extended-release (ER) is an atypical antipsychotic indicated for the treatment of schizophrenia which utilizes a patented oral osmotic system technology that provides constant drug delivery over the course of the day. The efficacy and safety of paliperidone ER in patients with schizophrenia have been established. This review focuses on the metabolic safety of paliperidone ER in patients with schizophrenia. Clinical trials have demonstrated a lack of significant change in lipid profiles with paliperidone ER; furthermore, reported incidences of glucose-related adverse events in clinical trials were very low and similar to those seen with placebo. While dose-related increases in bodyweight of 1–2 kg have been observed with paliperidone ER, there are few reports of clinically relevant increases in bodyweight during treatment. Placebo-controlled trials indicate that the risk of developing metabolic disorders with paliperidone ER is low and similar to that seen with placebo. Furthermore, the ER formulation of paliperidone may offer potential advantages over atypical antipsychotics such as risperidone, particularly with regard to side effects and compliance, but comparative studies are needed.

Notes

Acknowledgments

The authors would like to thank Stephanie Blick and Simone Boniface of inScience Communications, Springer Healthcare, for medical writing assistance in the preparation of this manuscript. This assistance was funded by Janssen-Cilag, Spain. Carlos Quilo is an employee of Janssen Cilag, Spain. Alfonso Rodríguez Martínez declares no conflicts of interest pertaining to this manuscript.

References

  1. 1.
    Andreasen NC. Symptoms, signs, and diagnosis of schizophrenia. Lancet. 1995;346(8973):477–81.PubMedCrossRefGoogle Scholar
  2. 2.
    Buckley PF. Treatment of schizophrenia: let’s talk dollars and sense. Am J Manag Care. 1998;4(3):369–83.PubMedGoogle Scholar
  3. 3.
    Bishara D, Taylor D. Upcoming agents for the treatment of schizophrenia: mechanism of action, efficacy and tolerability. Drugs. 2008;68(16):2269–92.PubMedCrossRefGoogle Scholar
  4. 4.
    Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004;161(2 Suppl):1–56.PubMedGoogle Scholar
  5. 5.
    Ellenbroek BA. Treatment of schizophrenia: a clinical and preclinical evaluation of neuroleptic drugs. Pharmacol Ther. 1993;57(1):1–78.PubMedGoogle Scholar
  6. 6.
    Schotte A, Janssen PF, Gommeren W, et al. Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996;124(1–2):57–73.CrossRefGoogle Scholar
  7. 7.
    Meltzer HY, Matsubara S, Lee JC. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values. J Pharmacol Exp Ther. 1989;251(1):238–46.PubMedGoogle Scholar
  8. 8.
    Meltzer HY, Matsubara S, Lee JC. The ratios of serotonin2 and dopamine2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacol Bull. 1989;25(3):390–2.PubMedGoogle Scholar
  9. 9.
    Casey DE, Zorn SH. The pharmacology of weight gain with antipsychotics. J Clin Psychiatry. 2001;62(Suppl 7):4–10.PubMedGoogle Scholar
  10. 10.
    Wetterling T. Bodyweight gain with atypical antipsychotics: a comparative review. Drug Saf. 2001;24(1):59–73.PubMedCrossRefGoogle Scholar
  11. 11.
    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
  12. 12.
    Fagan AL, Kissack JC, Augustin BG. Adverse events medication treatment costs in a chronically, severely mentally ill forensics population. Clin Schizophr Relat Psychoses. 2008;2(2):158–62.CrossRefGoogle Scholar
  13. 13.
    Canuso CM, Youssef EA, Bossie CA, et al. Paliperidone extended-release tablets in schizophrenia patients previously treated with risperidone. Int Clin Psychopharmacol. 2008;23(4):209–15.PubMedCrossRefGoogle Scholar
  14. 14.
    Atmaca M, Kuloglu M, Tezcan E, et al. Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics. J Clin Psychiatry. 2003;64(5):598–604.PubMedCrossRefGoogle Scholar
  15. 15.
    Kane J, Canas F, Kramer M, et al. Treatment of schizophrenia with paliperidone extended-release tablets: a 6-week placebo-controlled trial. Schizophr Res. 2007;90(1–3):147–61.PubMedCrossRefGoogle Scholar
  16. 16.
    McIntyre RS, McCann SM, Kennedy SH. Antipsychotic metabolic effects: weight gain, diabetes mellitus, and lipid abnormalities. Can J Psychiatry. 2001;46(3):273–81.PubMedGoogle Scholar
  17. 17.
    Nasrallah HA. Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008;13(1):27–35.PubMedCrossRefGoogle Scholar
  18. 18.
    Wirshing DA, Boyd JA, Meng LR, et al. The effects of novel antipsychotics on glucose and lipid levels. J Clin Psychiatry. 2002;63(10):856–65.PubMedCrossRefGoogle Scholar
  19. 19.
    Meyer JM, Koro CE. The effects of antipsychotic therapy on serum lipids: a comprehensive review. Schizophr Res. 2004;70(1):1–17.PubMedCrossRefGoogle Scholar
  20. 20.
    Hardy TA, Marquez E, Kryzhanovskaya L, et al. Cross-sectional comparison of fasting lipids in normoglycemic patients with schizophrenia during chronic treatment with olanzapine, risperidone, or typical antipsychotics. J Clin Psychopharmacol. 2006;26(4):405–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Meyer JM. A retrospective comparison of weight, lipid, and glucose changes between risperidone- and olanzapine-treated inpatients: metabolic outcomes after 1 year. J Clin Psychiatry. 2002;63(5):425–33.PubMedCrossRefGoogle Scholar
  22. 22.
    Su KP, Wu PL, Pariante CM. A crossover study on lipid and weight changes associated with olanzapine and risperidone. Psychopharmacology (Berl). 2005;183(3):383–6.CrossRefGoogle Scholar
  23. 23.
    Wu RR, Zhao JP, Zhai JG, et al. Sex difference in effects of typical and atypical antipsychotics on glucose-insulin homeostasis and lipid metabolism in first-episode schizophrenia. J Clin Psychopharmacol. 2007;27(4):374–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Khalili H, Dashti-Khavidaki S, Okhovatpour H, et al. Effects of risperidone on lipid profile. Ann Pharmacother. 2007;41(5):899–900.PubMedCrossRefGoogle Scholar
  25. 25.
    Lindenmayer JP, Nathan AM, Smith RC. Hyperglycemia associated with the use of atypical antipsychotics. J Clin Psychiatry. 2001;62(Suppl 23):30–8.PubMedGoogle Scholar
  26. 26.
    Allison DB, Mentore JL, Heo M, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999;156(11):1686–96.PubMedGoogle Scholar
  27. 27.
    Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005;19(Suppl 1):1–93.PubMedGoogle Scholar
  28. 28.
    Schooler NR, Gharabawi G, Bossie C, et al. A “virtual” comparison of paliperidone ER and oral risperidone in patients with schizophrenia [abstract]. 45th Annual Meeting of the American College of Neuropharmacology. 2006 Dec 3–7, Hollywood, p. S241–42.Google Scholar
  29. 29.
    Liberty IF, Todder D, Umansky R, et al. Atypical antipsychotics and diabetes mellitus: an association. Isr Med Assoc J. 2004;6(5):276–9.PubMedGoogle Scholar
  30. 30.
    Buckley PF. Update on the treatment and management of schizophrenia and bipolar disorder. CNS Spectr. 2008;13(2 Suppl 1):1–10 (quiz 1–2).Google Scholar
  31. 31.
    Kroeze WK, Hufeisen SJ, Popadak BA, et al. H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology. 2003;28(3):519–26.PubMedCrossRefGoogle Scholar
  32. 32.
    Matsui-Sakata A, Ohtani H, Sawada Y. Receptor occupancy-based analysis of the contributions of various receptors to antipsychotics-induced weight gain and diabetes mellitus. Drug Metab Pharmacokinet. 2005;20(5):368–78.PubMedCrossRefGoogle Scholar
  33. 33.
    Davidson M, Emsley R, Kramer M, et al. Efficacy, safety and early response of paliperidone extended-release tablets (paliperidone ER): results of a 6-week, randomized, placebo-controlled study. Schizophr Res. 2007;93(1–3):117–30.PubMedCrossRefGoogle Scholar
  34. 34.
    Marder SR, Kramer M, Ford L, et al. Efficacy and safety of paliperidone extended-release tablets: results of a 6-week, randomized, placebo-controlled study. Biol Psychiatry. 2007;62(12):1363–70.PubMedCrossRefGoogle Scholar
  35. 35.
    Meltzer HY, Bobo WV, Nuamah IF, et al. Efficacy and tolerability of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 6-week, placebo-controlled studies. J Clin Psychiatry. 2008;69(5):817–29.PubMedCrossRefGoogle Scholar
  36. 36.
    Emsley R, Berwaerts J, Eerdekens M, et al. Efficacy and safety of oral paliperidone extended-release tablets in the treatment of acute schizophrenia: pooled data from three 52-week open-label studies. Int Clin Psychopharmacol. 2008;23(6):343–56.PubMedCrossRefGoogle Scholar
  37. 37.
    Ortho-McNeil-Janssen Pharmaceuticals, Inc. Invega™ (paliperidone) extended-release tablets: US prescribing information [online]. Available from http://invega.com/assets/prescribing-information.pdf. Accessed 24 May 2011.
  38. 38.
    European Medicines Agency. Invega™ (paliperidone): summary of product characteristics. 2006. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000746/WC500034925.pdf. Accessed 21 Oct 2013.
  39. 39.
    Luthringer R, Staner L, Noel N, et al. A double-blind, placebo-controlled, randomized study evaluating the effect of paliperidone extended-release tablets on sleep architecture in patients with schizophrenia. Int Clin Psychopharmacol. 2007;22(5):299–308.PubMedCrossRefGoogle Scholar
  40. 40.
    Tzimos A, Samokhvalov V, Kramer M, et al. Safety and tolerability of oral paliperidone extended-release tablets in elderly patients with schizophrenia: a double-blind, placebo-controlled study with six-month open-label extension. Am J Geriatr Psychiatry. 2008;16(1):31–43.PubMedCrossRefGoogle Scholar
  41. 41.
    Schreiner A, Tessier C, Hoeben D, et al. A prospective randomized controlled trial of paliperidone ER versus oral olanzapine in patients with schizophrenia. 15th Winter Workshop in Psychoses (WWP); 2009 Nov 15–18; Barcelona.Google Scholar
  42. 42.
    Jeppesen J, Hein HO, Suadicani P, et al. Low triglycerides-high high-density lipoprotein cholesterol and risk of ischemic heart disease. Arch Intern Med. 2001;161(3):361–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Kramer M, Simpson G, Maciulis V, et al. Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia: a randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol. 2007;27(1):6–14.PubMedCrossRefGoogle Scholar
  44. 44.
    European Medicines Agency. Risperdal (risperidone): summary of product characteristics. 2011. http://www.medicines.org.uk/EMC/medicine/12818/SPC/Risperdal+Tablets,+Liquid+%26+Quicklet/. Accessed 24 Oct 2013.
  45. 45.
    Jones MP, Nicholl D, Trakas K. Efficacy and tolerability of paliperidone ER and other oral atypical antipsychotics in schizophrenia. Int J Clin Pharmacol Ther. 2010;48(6):383–99.PubMedCrossRefGoogle Scholar
  46. 46.
    Janicak PG, Winans EA. Paliperidone ER: a review of the clinical trial data. Neuropsychiatr Dis Treat. 2007;3(6):869–97.PubMedGoogle Scholar
  47. 47.
    Casey DE. Dyslipidemia and atypical antipsychotic drugs. J Clin Psychiatry. 2004;65(Suppl 18):27–35.PubMedGoogle Scholar
  48. 48.
    Citrome L. Paliperidone: quo vadis? Int J Clin Pract. 2007;61(4):653–62.PubMedCrossRefGoogle Scholar
  49. 49.
    Vermeir M, Naessens I, Remmerie B, et al. Absorption, metabolism, and excretion of paliperidone, a new monoaminergic antagonist, in humans. Drug Metab Dispos. 2008;36(4):769–79.PubMedCrossRefGoogle Scholar
  50. 50.
    Degmecic D, Pozgain I, Filakovic P. Psychoeducation and compliance in the treatment of patients with schizophrenia. Coll Antropol. 2007;31(4):1111–5.PubMedGoogle Scholar
  51. 51.
    Janicak PG, Wu JH, Mao L. Hospitalization rates before and after initiation of paliperidone ER in patients with schizophrenia: results from open-label extensions of the US double-blind trials. Curr Med Res Opin. 2008;24(6):1807–15.PubMedCrossRefGoogle Scholar
  52. 52.
    Sun SX, Liu GG, Christensen DB, et al. Review and analysis of hospitalization costs associated with antipsychotic nonadherence in the treatment of schizophrenia in the United States. Curr Med Res Opin. 2007;23(10):2305–12.PubMedCrossRefGoogle Scholar
  53. 53.
    Kinon BJ, Lieberman JA. Mechanisms of action of atypical antipsychotic drugs: a critical analysis. Psychopharmacology (Berl). 1996;124(1–2):2–34.CrossRefGoogle Scholar
  54. 54.
    Schreiner A, Niehaus D, Shuriquie NA, et al. Metabolic effects of paliperidone extended release versus oral olanzapine in patients with schizophrenia: a prospective, randomized, controlled trial. J Clin Psychopharmacol. 2012;32(4):449–57.PubMedCrossRefGoogle Scholar
  55. 55.
    Arnt J, Skarsfeldt T. Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence. Neuropsychopharmacology. 1998;18(2):63–101.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Alfonso Rodríguez-Martínez
    • 1
  • Carlos Guzmán Quilo
    • 2
  1. 1.Centro ForumBarcelonaSpain
  2. 2.Medical DepartmentJanssen CilagMadridSpain

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