, Volume 72, Issue 8, pp 1137–1160 | Cite as

Extended-Release Intramuscular Paliperidone Palmitate

A Review of its Use in the Treatment of Schizophrenia
  • Natalie J. CarterEmail author
Adis Drug Evaluation


Extended-release intramuscular paliperidone palmitate (Xeplion®; Invega® Sustenna®) [henceforth referred to as intramuscular paliperidone palmitate] is a long-acting injectable (LAI) formulation of the well established atypical anti-psychotic agent paliperidone (9-hydroxyrisperidone), which is the major active metabolite of risperidone. This article reviews, from an EU perspective, the therapeutic efficacy and tolerability of intramuscular paliperidone palmitate in the treatment of adults with schizophrenia, and the pharmacology of paliperidone that is relevant to the intramuscular formulation.

Intramuscular paliperidone palmitate 25–150mg equivalents (mg eq.) effectively reduced symptoms of schizophrenia in most short-term (9–13 weeks) placebo-controlled trials, as demonstrated by improvements in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to endpoint that were significantly greater in intramuscular paliperidone palmitate than placebo recipients. The onset of clinical response was 8 days in patients who received the recommended initial 150mg eq. dose of intramuscular paliperidone palmitate into the deltoid muscle on day 1.

In a longer-term (24-week maintenance phase and variable length double-blind phase) placebo-controlled trial, intramuscular paliperidone palmitate was associated with a significantly longer time to relapse than placebo in patients with schizophrenia at a preplanned interim analysis conducted after 68 relapse events. Because of these favourable results, the study was terminated early.

In two 13-week trials, one of which was conducted in Chinese patients, intramuscular paliperidone palmitate administered using the recommended initiation dosage regimen was noninferior to LAI-risperidone in patients with schizophrenia in terms of the between-group treatment difference (intramuscular paliperidone palmitate vs LAI-risperidone) for the mean change from baseline to endpoint in PANSS total score.

The tolerability of intramuscular paliperidone palmitate was generally acceptable in clinical trials of schizophrenia. No new safety concerns were revealed compared with oral paliperidone, except for injection site-related reactions.

In conclusion, intramuscular paliperidone palmitate is a useful option for the treatment of patients with schizophrenia.


Schizophrenia Risperidone Antipsychotic Agent Paliperidone Gluteal Muscle 
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  1. 1.
    National Institute for Health and Clinical Excellence. Schizophrenia: core interventions in the treatment and management of schizophrenia in adults in primary and secondary care (updated edition). National clinical guideline number 82 [online]. Available from URL: [Accessed 2012 Jan 20]
  2. 2.
    Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004 Feb; 161 (2 Suppl.): 1–56PubMedCrossRefGoogle Scholar
  3. 3.
    Auquier P, Lancon C, Rouillon F, et al. Mortality in schizophrenia. Pharmacoepidemiol Drug Saf 2006 Oct; 15 (12): 873–9PubMedCrossRefGoogle Scholar
  4. 4.
    Robinson D, Woerner MG, Alvir JMJ, et al. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry 1999; 56 (3): 241–7PubMedCrossRefGoogle Scholar
  5. 5.
    The Scottish Schizophrenia Research Group. The Scottish first episode schizophrenia study VIII. Five-year follow-up: clinical and psychosocial findings. Br J Psychiatry 1992 Oct; 161 (4): 496–500Google Scholar
  6. 6.
    Gilday E, Nasrallah HA. Clinical pharmacology of paliperidone palmitate a parenteral long-acting formulation for the treatment of schizophrenia. Rev Recent Clin Trials 2012; 7 (1): 2–9PubMedCrossRefGoogle Scholar
  7. 7.
    Nasrallah HA. The case for long-acting antipsychotic agents in the post-CATIE era. Acta Psychiatr Scand 2007; 115: 260–7PubMedCrossRefGoogle Scholar
  8. 8.
    Goff DC, Hill M, Freudenreich O. Strategies for improving treatment adherence in schizophrenia and schizoaffective disorder. J Clin Psychiatry 2010; 71 Suppl. 2: 20–6PubMedCrossRefGoogle Scholar
  9. 9.
    Janssen-Cilag International NV. Paliperidone palmitate 25, 50, 75, 100, and 150mg prolonged-release suspension for injection (Xeplion®): EU summary of product characteristics [online]. Available from URL: [Accessed 2011 Oct 6]
  10. 10.
    Ortho-McNeil-Janssen Pharmaceuticals. Paliperidone palmitate extended-release injectable suspension for intramuscular use (Invega Sustenna®): US prescribing information [online]. Available from URL: [Accessed 2012 Jan 10]
  11. 11.
    Janssen-Cilag International NV. Invega® (paliperidone) prolonged-release tablets: EU summary of product characteristics [online]. Available from URL: [Accessed 2012 Jan 13]
  12. 12.
    Ortho-McNeil-Janssen Pharmaceuticals. Invega® (paliperidone) extended-release tablets: US prescribing information [online]. Available from URL: [Accessed 2012 Jan 13]
  13. 13.
    Chwieduk CM, Keating GM. Paliperidone extended release: a review of its use in the management of schizophrenia. Drugs 2010; 70 (10): 1295–317PubMedCrossRefGoogle Scholar
  14. 14.
    Yang LP, Plosker GL. Paliperidone extended release. CNS Drugs 2007; 21 (5): 417–25; discussion 426–7PubMedCrossRefGoogle Scholar
  15. 15.
    Taylor D. Psychopharmacology and adverse effects of antipsychotic long-acting injections: a review. Br J Psychiatry 2009; 195 (5 Suppl.): S13–9Google Scholar
  16. 16.
    Gopal S, Gassmann-Mayer C, Palumbo J, et al. Practical guidance for dosing and switching paliperidone palmitate treatment in patients with schizophrenia. Curr Med Res Opin 2010; 26 (2): 377–87PubMedCrossRefGoogle Scholar
  17. 17.
    European Medicines Agency. Paliperidone palmitate (Xeplion®): European public assessment report [online]. Available from URL: [Accessed 2011 Oct7]
  18. 18.
    European Medicines Agency. Invega® (paliperidone prolonged-release tablets): scientific discussion [online]. Available from URL: [Accessed 2012 Jan 9]
  19. 19.
    Karlsson P, Dencker E, Nyberg S, et al. Pharmacokinetics and dopamine D2 and serotonin 5-HT2A receptor occupancy of paliperidone in healthy subjects: two open-label, single-dose studies [abstract no. PIII-57]. Clin Pharmacol Ther 2006 Feb; 79 (2): P74Google Scholar
  20. 20.
    Arakawa R, Ito H, Takano A, et al. Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia. Psychopharmacology (Berl) 2008 Apr; 197 (2): 229–35CrossRefGoogle Scholar
  21. 21.
    Melkersson K, Dahl M-L. Adverse metabolic effects associated with atypical antipsychotics: literature review and clinical implications. Drugs 2004; 64 (7): 701–23PubMedCrossRefGoogle Scholar
  22. 22.
    Gopal S, Hough DW, Xu H, et al. Efficacy and safety of paliperidone palmitate in adult patients with acutely symptomatic schizophrenia: a randomized, double-blind, placebo-controlled, dose-response study. Int Clin Psycho-pharmacol 2010; 25 (5): 247–56CrossRefGoogle Scholar
  23. 23.
    Nasrallah HA, Gopal S, Gassmann-Mayer C, et al. A controlled, evidence-based trial of paliperidone palmitate, a long-acting injectable antipsychotic, in schizophrenia. Neuropsychopharmacology 2010; 35 (10): 2072–82PubMedCrossRefGoogle Scholar
  24. 24.
    Kramer M, Litman R, Hough D, et al. Paliperidone palmitate, a potential long-acting treatment for patients with schizophrenia: results of a randomized, double-blind, placebo-controlled efficacy and safety study. Int J Neuro-psychopharmacol 2010; 13 (5): 635–47Google Scholar
  25. 25.
    Pandina GJ, Lindenmayer JP, Lull J, et al. A randomized, placebo-controlled study to assess the efficacy and safety of 3 doses of paliperidone palmitate in adults with acutely exacerbated schizophrenia. J Clin Psychopharmacol 2010 Jun; 30 (3): 235–44PubMedCrossRefGoogle Scholar
  26. 26.
    Pandina G, Lane R, Gopal S, et al. A double-blind study of paliperidone palmitate and risperidone long-acting injectable in adults with schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 2011; 35 (1): 218–26CrossRefGoogle Scholar
  27. 27.
    Schreiner A, Korcsog P, Niehaus D, et al. A prospective randomized controlled trial of paliperidone ER verus oral olanzapine in patients with schizophrenia [abstract]. Int Clin Psychopharmacol 2011 Sep; 26 e-Suppl. 1: e67-8Google Scholar
  28. 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 Sep; 22 (5): 299–308PubMedCrossRefGoogle Scholar
  29. 29.
    Cleton A, Rossenu S, Hough D, et al. Assessment of the dose proportionality of paliperidone palmitate 25, 50, 100 and 150mg eq., a new long-acting injectable antipsychotic following administration in the deltoid or gluteal muscles [abstract no. PI-74]. Clin Pharmacol Ther 2008 Mar; 83 Suppl. 1: S31Google Scholar
  30. 30.
    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): 585–600PubMedCrossRefGoogle Scholar
  31. 31.
    Li H, Rui Q, Ning X, et al. A comparative study of paliperidone palmitate and risperidone long-acting injectable therapy in schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 2011; 35 (4): 1002–8CrossRefGoogle Scholar
  32. 32.
    Hough D, Gopal S, Vijapurkar U, et al. Paliperidone palmitate maintenance treatment in delaying the time-to-relapse in patients with schizophrenia: a randomized, double-blind, placebo-controlled study. Schizophr Res 2010 Feb; 116 (2–3): 107–17Google Scholar
  33. 33.
    Fleischhacker WW, Gopal S, Lane R, et al. A randomized trial of paliperidone palmitate and risperidone long-acting injectable in schizophrenia. Int J Neuropsychopharmacol 2012; 15 (1): 107–118. Plus supplementary material available from URL: [Accessed 2012 Jan 17]CrossRefGoogle Scholar
  34. 34.
    Bossie CA, Sliwa JK, Ma Y-W, et al. 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 May 10; 11: 79Google Scholar
  35. 35.
    Alphs L, Bossie CA, Sliwa JK, et al. Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial. Ann Gen Psychiatry 2011 Apr 11; 10: 12Google Scholar
  36. 36.
    Sliwa JK, Bossie CA, Ma Y-W, et al. Effects of acute paliperidone palmitate treatment in subjects with schizophrenia recently treated with oral risperidone. Schizophr Res 2011; 132 (1): 28–34PubMedCrossRefGoogle Scholar
  37. 37.
    Gopal S, Vijapurkar U, Lim P, et al. A 52-week open-label study of the safety and tolerability of paliperidone palmitate in patients with schizophrenia. J Psychopharmacol 2011; 25 (5): 685–97PubMedCrossRefGoogle Scholar
  38. 38.
    Kozma CM, Slaton T, Dirani R, et al. Changes in schizophrenia-related hospitalization and ER use among patients receiving paliperidone palmitate: results from a clinical trial with a 52-week open-label extension (OLE). Curr Med Res Opin 2011; 27 (8): 1603–11PubMedCrossRefGoogle Scholar
  39. 39.
    Gopal S, Pandina G, Lane R, et al. A post-hoc comparison of paliperidone palmitate to oral risperidone during initiation of long-acting risperidone injection in patients with acute schizophrenia. Innov Clin Neurosci 2011 Aug; 8 (8): 26–33PubMedGoogle Scholar
  40. 40.
    Hough D, Lindenmayer J-P, Gopal S, et al. Safety and tolerability of deltoid and gluteal injections of paliperidone palmitate in schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 2009; 33 (6): 1022–31CrossRefGoogle Scholar
  41. 41.
    Alphs L, Gopal S, Karcher K, et al. Are the long-acting intramuscular formulations of risperidone or paliperidone palmitate associated with post-injection delirium/sedation syndrome? An assessment of safety databases. Curr Drug Saf 2011; 6 (1): 43–5PubMedCrossRefGoogle Scholar
  42. 42.
    Agid O, Foussias G, Remington G. Long-acting injectable antipsychotics in the treatment of schizophrenia: their role in relapse prevention. Expert Opin Pharmacother 2010; 11 (14): 2301–17PubMedCrossRefGoogle Scholar
  43. 43.
    Lundbeck Ltd. Depixol® (flupentixol decanoate) injection: UK summary of product characteristics [online]. Available from URL: [Accessed 2012 Jan 17]
  44. 44.
    Sanofi-Aventis. Modecate® (fluphenazine decanoate) concentrate injection 100mg/mL: UK summary of product characteristics [online]. Available from URL: [Accessed 2012 Jan 17]
  45. 45.
    Janssen-Cilag Ltd. Haldol® decanoate (haloperidol decanoate) 50 and 100mg/mL: UK summary of product characteristics [online]. Available from URL: [Accessed 2012 Jan 17]
  46. 46.
    Sanofi-Aventis. Piportil® (pipotiazine palmitate) depot 50mg/mL solution for injection: UK summary of product characteristics [online]. Available from URL: [Accessed 2012 Jan 17]
  47. 47.
    Lundbeck Ltd. Clopixol® (zuclopenthixol decanoate) solution for injection: UK summary of product characteristics [online]. Available from URL: [Accessed 2012 Jan 17]
  48. 48.
    Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005 Sep; 353 (12): 1209–23PubMedCrossRefGoogle Scholar
  49. 49.
    Kane JM, Garcia-Ribera C. Clinical guideline recommendations for antipsychotic long-acting injections. Br J Psychiatry 2009 Nov; 195 (52): s63–7Google Scholar
  50. 50.
    Fleischhacker WW. Second-generation antipsychotic long-acting injections: systematic review. Br J Psychiatry 2009; 195 (5 Suppl.): S29–36Google Scholar
  51. 51.
    Janssen-Cilag Ltd. Risperdal Consta (risperidone) powder and solvent for prolonged-release suspension for injection: UK summary of product characteristics [online]. Available from URL: [Accessed 2012 Jan 17]
  52. 52.
    Eli Lilly Nederland BV. Zypadhera (olanzapine pamoate) powder and solvent for prolonged release suspension for injection: EU summary of product characteristics [online]. Available from URL: [Accessed 2012 Jan 17]
  53. 53.
    Citrome L. Paliperidone palmitate: review of the efficacy, safety and cost of a new second-generation depot antipsychotic medication. Int J Clin Pract 2010; 64 (2): 216–39PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  1. 1.AdisAucklandNew Zealand

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