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Paliperidone

A Review of Clinical Trial Data and Clinical Implications

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Abstract

Paliperidone, 9-hydroxy-risperidone, is the major metabolite of the atypical antipsychotic risperidone and is available in an oral extended-release (ER) formulation. Paliperidone ER was approved for treating schizophrenia in 2006, and in 2009 it became the first atypical antipsychotic licensed for treating schizoaffective disorder.

The short-term efficacy, safety and tolerability of paliperidone ER for patients with schizophrenia were demonstrated in three pivotal 6-week, ran domized, double-blind, placebo-controlled studies. Data from the long-term trial showed that paliperidone ER is also effective in preventing relapse of schizophrenia. Two randomized, placebo-controlled, short-term studies have documented the efficacy and tolerability of paliperidone ER in the treatment of schizoaffective disorder, but no long-term or maintenance study has been conducted in patients with schizoaffective disorder. Two 3-week, randomized, double-blind, placebo-controlled studies showed that paliperidone ER is significantly superior to placebo for treating patients with bipolar disorder, but the results were driven by certain subpopulations. Limited evidence suggests that paliperidone ER can potentially be superior to quetiapine and risperidone. However, few direct head-to-head comparisons between paliperidone ER and other antipsychotics have been conducted to confirm these results.

The distinctive pharmacological characteristics of paliperidone ER, in cluding smooth fluctuations in plasma drug concentrations, predominantly renal excretion, low risk of causing hepatic impairment and low drug-drug interaction, might provide important clinical advantages compared with ris peridone. However, certain side effects require clinical attention. The rate of extrapyramidal side effects was considerably higher than that of a placebo at doses ≥9 mg/day. The risks for orthostatic hypotension, prolongation of the corrected QT interval and hyperprolactinaemia are also concerns.

This review summarizes the currently published data on paliperidone ER for treating patients with schizophrenia, schizoaffective disorder and bipolar disorder, and suggests its appropriate use in clinical practice.

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References

  1. Rice DP. The economic impact of schizophrenia. J Clin Psychiatry 1999; 60 Suppl. 1: 4–6; discussion 28–30

    PubMed  Google Scholar 

  2. Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004; 161: 1–56

    Article  PubMed  Google Scholar 

  3. Correll CU, Leucht S, Kane JM. Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies. Am J Psychiatry 2004; 161: 414–25

    Article  PubMed  Google Scholar 

  4. Davis JM, Chen N, Glick ID. A meta-analysis of the efficacy of second-generation antipsychotics. Arch Gen Psychiatry 2003; 60: 553–64

    Article  CAS  PubMed  Google Scholar 

  5. Stroup TS, McEvoy JP, Swartz MS, et al. The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: schizophrenia trial design and protocol development. Schizophr Bull 2003; 29: 15–31

    Article  PubMed  Google Scholar 

  6. Johnsen E, Jorgensen HA. Effectiveness of second generation antipsychotics: a systematic review of randomized trials. BMC Psychiatry 2008; 8: 31

    Article  PubMed Central  PubMed  Google Scholar 

  7. Ortho-McNeil-Janssen Pharmaceuticals. INVEGA® (paliperidone) extended-release tablets. Last updated 2011 Jan [online]. Available from URL: http://janssencns.com/shared/pi/invega/invega.pdf [Accessed 2012 Jan 1]

  8. Berwaerts J, Lane R, Nuamah IF, et al. Paliperidone extended-release as adjunctive therapy to lithium or valproate in the treatment of acute mania: a randomized, placebo-controlled study. J Affect Disord 2011; 129: 252–60

    Article  CAS  PubMed  Google Scholar 

  9. Vieta E, Nuamah IF, Lim P, et al. A randomized, placebo- and active-controlled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorder. Bipolar Disord 2010; 12: 230–43

    Article  CAS  PubMed  Google Scholar 

  10. Berwaerts J, Melkote R, Nuamah I, et al. A randomized, placebo- and active-controlled study of paliperidone extended-release as maintenance treatment in patients with bipolar I disorder after an acute manic or mixed episode. J Affect Disord 2012; 138: 247–58

    Article  CAS  PubMed  Google Scholar 

  11. Johnson & Johnson Pharmaceutical Research & Development LLC. A study to evaluate the effectiveness and safety of extended-release (ER) paliperidone compared with placebo in delaying the recurrence of symptoms in bipolar I disorder [online]. Available from http://www.clinicaltrials.gov/ct2/show/NCT00490971 [Accessed 2011 Oct 1]

  12. Shayegan DK, Stahl SM. Atypical antipsychotics: matching receptor profile to individual patient’ clinical profile. CNS Spectr 2004; 9: 6–14

    PubMed  Google Scholar 

  13. Seeman P. An update of fast-off dopamine D2 atypical antipsychotics. Am J Psychiatry 2005; 162: 1984–5

    Article  PubMed  Google Scholar 

  14. van Beijsterveldt LE, Geerts RJ, Leysen JE, et al. Regional brain distribution of risperidone and its active metabolite 9-hydroxy-risperidone in the rat. Psychopharmacology (Berl) 1994; 114: 53–62

    Article  Google Scholar 

  15. Boom S, Talluri K, Janssens L, et al. Single- and multiple-dose pharmacokinetics and dose proportionality of the psychotropic agent paliperidone extended release. J Clin Pharmacol 2009; 49: 1318–30

    Article  CAS  PubMed  Google Scholar 

  16. Invega. 28 August 2010 [online]. Available from URL: http://www.emea.europa.eu/humandocs/Humans/EPAR/invega/invega.htm [Accessed 2012 Jun 18]

  17. Nesvag R, Hendset M, Refsum H, et al. Serum concentrations of risperidone and 9-OH risperidone following intramuscular injection of long-acting risperidone compared with oral risperidone medication. Acta Psychiatr Scand 2006; 114: 21–6

    Article  CAS  PubMed  Google Scholar 

  18. Mannens G, Meuldermans W, Snoeck E, et al. Plasma protein binding of risperidone and its distribution in blood. Psychopharmacology (Berl) 1994; 114: 566–72

    Article  CAS  Google Scholar 

  19. Berwaerts J, Cleton A, Herben V, et al. The effects of par-oxetine on the pharmacokinetics of paliperidone extended-release tablets. Pharmacopsychiatry 2009; 42: 158–63

    Article  CAS  PubMed  Google Scholar 

  20. Thyssen A, Cleton A, Talluri K, et al. No pharmacokinetic interaction between paliperidone extended-release tablets and trimethoprim in healthy subjects. Hum Psychopharmacol 2009; 24: 532–9

    Article  CAS  PubMed  Google Scholar 

  21. d’Amato T, Rochet T, Dalery J, et al. Relationship between symptoms rated with the Positive and Negative Syndrome Scale and brain measures in schizophrenia. Psychiatry Res 1992; 44: 55–62

    Article  PubMed  Google Scholar 

  22. Magnusson MO, Dahl ML, Cederberg J, et al. Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin. Clin Pharmacol Ther 2008; 84: 52–62

    Article  CAS  PubMed  Google Scholar 

  23. Boom S, Thyssen A, Crauwels H, et al. The influence of hepatic impairment on the pharmacokinetics of paliper idone. Int J Clin Pharmacol Ther 2009; 47: 606–16

    Article  CAS  PubMed  Google Scholar 

  24. 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: 147–61

    Article  CAS  PubMed  Google Scholar 

  25. 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: 1363–70

    Article  CAS  PubMed  Google Scholar 

  26. 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, pla cebo-controlled study. Schizophr Res 2007; 93: 117–30

    Article  PubMed  Google Scholar 

  27. Canuso C YE, Dirks B, et al. Paliperidone extended-release in severely ill patients with schizophrenia. New York (NY): Presented at the Institute on Psychiatric Services, 2006 October 5–8

  28. 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: 299–308

    Article  PubMed  Google Scholar 

  29. Nussbaum AM, Stroup TS. Paliperidone for treatment of schizophrenia. Schizophr Bull 2008; 34: 419–22

    Article  PubMed  Google Scholar 

  30. Canuso CM, Turkoz I, Sheehan JJ, et al. Efficacy and safety of paliperidone extended-release in schizophrenia patients with prominent affective symptoms. J Affect Disord 2010; 120: 193–9

    Article  CAS  PubMed  Google Scholar 

  31. Canuso CM, Bossie CA, Turkoz I, et al. Paliperidone extended-release for schizophrenia: effects on symptoms and functioning in acutely ill patients with negative symptoms. Schizophr Res 2009; 113: 56–64

    Article  CAS  PubMed  Google Scholar 

  32. 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: 6–14

    Article  CAS  PubMed  Google Scholar 

  33. 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: 343–56

    Article  PubMed  Google Scholar 

  34. Canuso CM, Lindenmayer JP, Kosik-Gonzalez C, et al. A randomized, double-blind, placebo-controlled study of 2 dose ranges of paliperidone extended-release in the treatment of subjects with schizoaffective disorder. J Clin Psychiatry 2010; 71: 587–98

    Article  CAS  PubMed  Google Scholar 

  35. Canuso CM, Schooler N, Carothers J, et al. Paliperidone extended-release in schizoaffective disorder: a randomized, controlled study comparing a flexible dose with placebo in patients treated with and without antidepressants and/or mood stabilizers. J Clin Psychopharmacol 2010; 30: 487–95

    Article  CAS  PubMed  Google Scholar 

  36. Canuso CM, Grinspan A, Kalali A, et al. Medication satisfaction in schizophrenia: a blinded-initiation study of paliperidone extended release in patients suboptimally responsive to risperidone. Int Clin Psychopharmacol 2010; 25: 155–64

    Article  PubMed  Google Scholar 

  37. Canuso CM, Youssef EA, Bossie CA, et al. Paliperidone extended-release tablets in schizophrenia patients previously treated with risperidone. Int Clin Psychopharmacol 2008; 23: 209–15

    Article  PubMed  Google Scholar 

  38. Turkoz I, Bossie CA, Lindenmayer JP, et al. Paliperidone ER and oral risperidone in patients with schizophrenia: a comparative database analysis. BMC Psychiatry 2011; 11: 21

    Article  PubMed Central  PubMed  Google Scholar 

  39. Canuso CM, Dirks B, Carothers J, et al. Randomized, double-blind, placebo-controlled study of paliperidone extended-release and quetiapine in inpatients with recently exacerbated schizophrenia. Am J Psychiatry 2009; 166: 691–701

    Article  PubMed  Google Scholar 

  40. Schreiner AKP, Niehaus D, et al. A prospective randomized controlled trial of paliperidone ER versus oral olanzapine in patients with schizophrenia [abstract no. SCH-3020]. 15th Biennial Winter Workshop on Psychoses; Nov 15–18; Barcelona 2009

    Google Scholar 

  41. 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: 31–43

    Article  PubMed  Google Scholar 

  42. Singh J, Robb A, Vijapurkar U, et al. A randomized, double-blind study of paliperidone extended-release in treatment of acute schizophrenia in adolescents. Biol Psychiatry 2011; 70: 1179–87

    Article  CAS  PubMed  Google Scholar 

  43. 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: 817–29

    Article  CAS  PubMed  Google Scholar 

  44. Hough DW, Natarajan J, Vandebosch A, et al. Evaluation of the effect of paliperidone extended release and quetiapine on corrected QT intervals: a randomized, double-blind, placebo-controlled study. Int Clin Psychopharmacol 2011; 26: 25–34

    Article  PubMed  Google Scholar 

  45. Marino J, Caballero J. Paliperidone extended-release for the treatment of schizophrenia. Pharmacotherapy 2008; 28: 1283–98

    Article  CAS  PubMed  Google Scholar 

  46. Harrington CA, English C. Tolerability of paliperidone: a meta-analysis of randomized, controlled trials. Int Clin Psychopharmacol 2010; 25: 334–41

    Article  PubMed  Google Scholar 

  47. Melkersson KI. Prolactin elevation of the antipsychotic risperidone is predominantly related to its 9-hydroxy meta bolite. Hum Psychopharmacol 2006; 21: 529–32

    Article  CAS  PubMed  Google Scholar 

  48. Melkersson K. Differences in prolactin elevation and related symptoms of atypical antipsychotics in schizophrenic patients. J Clin Psychiatry 2005; 66: 761–7

    Article  CAS  PubMed  Google Scholar 

  49. Knegtering R, Baselmans P, Castelein S, et al. Predominant role of the 9-hydroxy metabolite of risperidone in elevating blood prolactin levels. Am J Psychiatry 2005; 162: 1010–2

    Article  PubMed  Google Scholar 

  50. Carney CP, Jones L, Woolson RF. Medical comorbidity in women and men with schizophrenia: a population-based controlled study. J Gen Intern Med 2006; 21: 1133–7

    Article  PubMed Central  PubMed  Google Scholar 

  51. Carney CP, Jones LE. Medical comorbidity in women and men with bipolar disorders: a population-based controlled study. Psychosom Med 2006; 68: 684–91

    Article  PubMed  Google Scholar 

  52. Kim JN, Lee Choi IG, et al. Paliperidone-induced leukopenia and neutropenia: a case report. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 284–5

    Article  PubMed  Google Scholar 

  53. Han C, Lee SJ, Pae CU. Paliperidone-associated atypical neuroleptic malignant syndrome: a case report. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 650–1

    Article  PubMed  Google Scholar 

  54. Chang JP, Huang CC, Su KP. Paliperidone overdose in a patient with schizophrenia [letter]. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 418

    Article  PubMed  Google Scholar 

  55. Risperidal®. Precribing information. Ortho-McNeil-Janssen Pharmaceuticals. 2011 January [online]. Available from URL: http://www.risperdal.com/sites/default/files/shared/pi/risperdal.pdf [Accessed 2012 Jun 18]

  56. Gray JARB. The pipeline and future of drug development in schizophrenia. Mol Psychiatry 2007; 12: 904–22

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Conflicts of interest: The authors have no conflicts of interest related to the content of this review.

Contributors: Chi-Un Pae, W. Wolfgang Fleischhacker and Sheng-Min Wang conceived the manuscript and contributed to the final version of the paper. Changsu Han, Soo-Jung Lee and Ashwin A. Patkar contributed to the writing of the paper and performed the data collection. All authors contributed to and approved the final manuscript.

There was no funding for the preparation of the manuscript.

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Correspondence to Chi-Un Pae MD, PhD.

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Wang, SM., Han, C., Lee, SJ. et al. Paliperidone. Clin Drug Invest 32, 497–512 (2012). https://doi.org/10.1007/BF03261901

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