Skip to main content
SpringerLink
Log in

Asenapine: A Review in Schizophrenia

  • Adis Drug Evaluation
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Asenapine (Saphris®, Sycrest®) is an atypical antipsychotic that is administered sublingually twice daily and is approved for schizophrenia in the USA, Japan and other countries, but not in the EU. This article reviews the pharmacology, clinical efficacy and tolerability profile of asenapine in the treatment of adults with schizophrenia. Clinical trials with asenapine have demonstrated efficacy in terms of both positive and negative symptoms of schizophrenia, although findings have not always been consistent. Across three short-term (6-week) studies in acute schizophrenia (including one in Asian patients), asenapine was generally superior to placebo and had broadly similar efficacy to active controls in improving total scores on the Positive and Negative Syndrome Scale. A meta-analysis of four short-term trials with asenapine (that also included a negative study and a failed trial) also showed significant benefit with asenapine over placebo. In longer-term trials and extensions (up to ≈3 years’ duration), asenapine was effective relative to placebo in preventing relapse in schizophrenia, but was less effective than olanzapine in patients with schizophrenia or schizoaffective disorder (according to intent-to-treat LOCF analysis). However, in two trials in patients with persistent negative symptoms of schizophrenia, asenapine and olanzapine were similarly effective in reducing negative symptoms at week 26, with asenapine providing better results than olanzapine at week 52 in one of the extensions. The most frequently reported adverse events with asenapine are somnolence, akathisia and oral hypoesthesia. Although potentially associated with more extrapyramidal symptoms, asenapine appears to have less weight gain and metabolic effects than some other antipsychotic agents, such as olanzapine.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Rossler W, Salize HJ, van Os J, et al. Size of burden of schizophrenia and psychotic disorders. Eur Neuropsychopharmacol. 2005;15(4):399–409.

    Article  PubMed  Google Scholar 

  2. Fusar-Poli P, Papanastasiou E, Stahl D, et al. Treatments of negative symptoms in schizophrenia: meta-analysis of 168 randomized placebo-controlled trials. Schizophr Bull. 2015;41(4):892–9.

    Article  PubMed  Google Scholar 

  3. Lewis DA, Lieberman JA. Catching up on schizophrenia: natural history and neurobiology. Neuron. 2000;28(2):325–34.

    Article  CAS  PubMed  Google Scholar 

  4. Saha S, Chant D, Welham J, et al. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005;2(5):e141.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Messias EL, Chen CY, Eaton WW. Epidemiology of schizophrenia: review of findings and myths. Psychiatr Clin North Am. 2007;30(3):323–38.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Cortese L, Bressan RA, Castle DJ, et al. Management of schizophrenia: clinical experience with asenapine. J Psychopharmacol. 2013;27(4 Suppl):14–22.

    Article  PubMed  Google Scholar 

  7. Villalta-Gil V, Vilaplana M, Ochoa S, et al. Neurocognitive performance and negative symptoms: are they equal in explaining disability in schizophrenia outpatients? Schizophr Res. 2006;87(1–3):246–53.

    Article  PubMed  Google Scholar 

  8. Miller BJ, Paschall CB 3rd, Svendsen DP. Mortality and medical comorbidity among patients with serious mental illness. Psychiatr Serv. 2006;57(10):1482–7.

    Article  PubMed  Google Scholar 

  9. Tandon R, Jibson MD. Efficacy of newer generation antipsychotics in the treatment of schizophrenia. Psychoneuroendocrinology. 2003;28(Suppl 1):9–26.

    Article  CAS  PubMed  Google Scholar 

  10. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382(9896):951–62.

    Article  CAS  PubMed  Google Scholar 

  11. De Hert M, Yu W, Detraux J. Body weight and metabolic adverse effects of asenapine, iloperidone, lurasidone, and paliperidone in the treatment of schizophrenia and bipolar disorder: a systematic review and exploratory meta-analysis. CNS Drugs. 2012;26:733–59.

    Article  PubMed  Google Scholar 

  12. Citrome L. A review of the pharmacology, efficacy and tolerability of recently approved and upcoming oral antipsychotics: an evidence-based medicine approach. CNS Drugs. 2013;27(11):879–911.

    Article  CAS  PubMed  Google Scholar 

  13. Rado J, Janicak PG. Pharmacological and clinical profile of recently approved second-generation antipsychotics: implications for treatment of schizophrenia in older patients. Drugs Aging. 2012;29(10):783–91.

    Article  CAS  PubMed  Google Scholar 

  14. Peuskens J, Pani L, Detraux J, et al. The effects of novel and newly approved antipsychotics on serum prolactin levels: a comprehensive review. CNS Drugs. 2014;28(5):421–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Wang SM, Han C, Lee SJ, et al. Asenapine, blonanserin, iloperidone, lurasidone, and sertindole: distinctive clinical characteristics of 5 novel atypical antipsychotics. Clin Neuropharmacol. 2013;36(6):223–38.

    Article  CAS  PubMed  Google Scholar 

  16. Werner FM, Covenas R. Safety of antipsychotic drugs: focus on therapeutic and adverse effects. Expert Opin Drug Saf. 2014;13(8):1031–42.

    Article  CAS  PubMed  Google Scholar 

  17. Actavis Inc. Saphris (asenapine) sublingual tablets: US prescribing information. 2015. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed 13 Jun 2016.

  18. Andree B, Halldin C, Vrijmoed-de Vries M, et al. Central 5-HT2A and D2 dopamine receptor occupancy after sublingual administration of ORG 5222 in healthy men. Psychopharmacology. 1997;131(4):339–45.

    Article  CAS  PubMed  Google Scholar 

  19. Marston HM, Young JW, Martin FDC, et al. Asenapine effects in animal models of psychosis and cognitive function. Psychopharmacology. 2009;206(4):699–714.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Elsworth JD, Groman SM, Jentsch DJ, et al. Asenapine effects on cognitive and monoamine dysfunction elicited by subchronic phencyclidine administration. Neuropharmacology. 2012;62(3):1442–52.

    Article  CAS  PubMed  Google Scholar 

  21. Jardemark K, Marcus MM, Shahid M, et al. Effects of asenapine on prefrontal N-methyl-d-aspartate receptor-mediated transmission: involvement of dopamine D1 receptors. Synapse. 2010;64(11):870–4.

    Article  CAS  PubMed  Google Scholar 

  22. Franberg O, Marcus MM, Svensson TH. Involvement of 5-HT2A receptor and α2-adrenoceptor blockade in the asenapine-induced elevation of prefrontal cortical monoamine outflow. Synapse. 2012;66(7):650–60.

    Article  CAS  PubMed  Google Scholar 

  23. Tarazi FI, Moran-Gates T, Wong EHF, et al. Asenapine induces differential regional effects on serotonin receptor subtypes. J Psychopharmacol (Oxf). 2010;24(3):341–8.

    Article  CAS  Google Scholar 

  24. Oosterhof CA, El Mansari M, Blier P. Asenapine alters the activity of monoaminergic systems following its subacute and long-term administration: an in vivo electrophysiological characterization. Eur Neuropsychopharmacol. 2015;25(4):531–43.

    Article  CAS  PubMed  Google Scholar 

  25. Ohyama M, Kondo M, Yamauchi M, et al. Asenapine reduces anxiety-related behaviours in rat conditioned fear stress model. Acta Neuropsychiatr. 2016. doi:10.1017/neu.2016.17.

    PubMed  Google Scholar 

  26. Tarazi FI, Neill JC. The preclinical profile of asenapine: clinical relevance for the treatment of schizophrenia and bipolar mania. Expert Opin Drug Discov. 2013;8(1):93–103.

    Article  CAS  PubMed  Google Scholar 

  27. Franberg O, Wiker C, Marcus MM, et al. Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia. Psychopharmacology. 2008;196(3):417–29.

    Article  CAS  PubMed  Google Scholar 

  28. Citrome L. Asenapine review, part I: chemistry, receptor affinity profile, pharmacokinetics and metabolism. Expert Opin Drug Metab Toxicol. 2014;10(6):893–903.

    Article  CAS  PubMed  Google Scholar 

  29. Mandrioli R, Protti M, Mercolini L. Novel atypical antipsychotics: metabolism and therapeutic drug monitoring (TDM). Curr Drug Metab. 2015;16(2):141–51.

    Article  CAS  PubMed  Google Scholar 

  30. Gerrits M, de Greef R, Peeters P. Effect of absorption site on the pharmacokinetics of sublingual asenapine in healthy male subjects. Biopharm Drug Dispos. 2010;31(5–6):351–7.

    CAS  PubMed  Google Scholar 

  31. Peeters P, Bockbrader H, Spaans E, et al. Asenapine pharmacokinetics in hepatic and renal impairment. Clin Pharmacokinet. 2011;50(7):471–81.

    Article  CAS  PubMed  Google Scholar 

  32. Dubovsky SL, Frobose C, Phiri P, et al. Short-term safety and pharmacokinetic profile of asenapine in older patients with psychosis. Int J Geriatr Psychiatry. 2012;27(5):472–82.

    Article  PubMed  Google Scholar 

  33. Gerrits MG, de Greef R, Dogterom P, et al. Valproate reduces the glucuronidation of asenapine without affecting asenapine plasma concentrations. J Clin Pharmacol. 2012;52(5):757–65.

    Article  CAS  PubMed  Google Scholar 

  34. Dogterom P, Schnabel PG, Timmer C, et al. Effect of carbamazepine on asenapine pharmacokinetics [abstract no. PII-44]. Clin Pharmacol Ther. 2008;83(Suppl 1):S55.

    Google Scholar 

  35. Potkin SG, Cohen M, Panagides J. Efficacy and tolerability of asenapine in acute schizophrenia: a placebo- and risperidone-controlled trial. J Clin Psychiatry. 2007;68(10):1492–500.

    Article  CAS  PubMed  Google Scholar 

  36. Kane JM, Cohen M, Zhao J, et al. Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia. J Clin Psychopharmacol. 2010;30(2):106–15.

    Article  CAS  PubMed  Google Scholar 

  37. Kinoshita T, Bai Y-M, Kim J-H, et al. Efficacy and safety of asenapine in Asian patients with an acute exacerbation of schizophrenia: a multicentre, randomized, double-blind, 6-week, placebo-controlled study. Psychopharmacology. 2016. doi:10.1007/s00213-016-4295-9.

    PubMed  Google Scholar 

  38. Citrome L. Asenapine review, part II: clinical efficacy, safety and tolerability. Expert Opin Drug Saf. 2014;13(6):803–30.

    CAS  PubMed  Google Scholar 

  39. Citrome L. Asenapine for schizophrenia and bipolar disorder: a review of the efficacy and safety profile for this newly approved sublingually absorbed second-generation antipsychotic. Int J Clin Pract. 2009;63(12):1762–84.

    Article  CAS  PubMed  Google Scholar 

  40. Pratts M, Citrome L, Grant W, et al. A single-dose, randomized, double-blind, placebo-controlled trial of sublingual asenapine for acute agitation. Acta Psychiatr Scand. 2014;130(1):61–8.

    Article  CAS  PubMed  Google Scholar 

  41. Szegedi A, Verweij P, Van Duijnhoven W, et al. Meta-analyses of the efficacy of asenapine for acute schizophrenia: comparisons with placebo and other antipsychotics. J Clin Psychiatry. 2012;73(12):1533–40.

    Article  CAS  PubMed  Google Scholar 

  42. Friberg LE, de Greef R, Kerbusch T, et al. Modeling and simulation of the time course of asenapine exposure response and dropout patterns in acute schizophrenia. Clin Pharmacol Ther. 2009;86(1):84–91.

    Article  CAS  PubMed  Google Scholar 

  43. Leucht S, Zhao J. Early improvement as a predictor of treatment response and remission in patients with schizophrenia: a pooled, post-hoc analysis from the asenapine development program. J Psychopharmacol. 2014;28(4):387–94.

    Article  PubMed  Google Scholar 

  44. Castle DJ, Jensen JKS. Management of depressive symptoms in schizophrenia: a pooled, post hoc analysis from the asenapine development program. Clin Schizophr Relat Psychoses. 2015;9(1):13–20.

    Article  PubMed  Google Scholar 

  45. Kane JM, Mackle M, Snow-Adami L, et al. A randomized placebo-controlled trial of asenapine for the prevention of relapse of schizophrenia after long-term treatment. J Clin Psychiatry. 2011;72(3):349–55.

    Article  PubMed  Google Scholar 

  46. Schoemaker J, Naber D, Vrijland P, et al. Long-term assessment of asenapine vs. olanzapine in patients with schizophrenia or schizoaffective disorder [erratum in Pharmacopsychiatry 2011;44:343]. Pharmacopsychiatry. 2010;43(4):138–46.

    Article  CAS  PubMed  Google Scholar 

  47. Schoemaker J, Stet L, Vrijland P, et al. Long-term efficacy and safety of asenapine or olanzapine in patients with schizophrenia or schizoaffective disorder: an extension study. Pharmacopsychiatry. 2012;45(5):196–203.

    CAS  PubMed  Google Scholar 

  48. Buchanan RW, Panagides J, Zhao J, et al. Asenapine versus olanzapine in people with persistent negative symptoms of schizophrenia. J Clin Psychopharmacol. 2012;32(1):36–45.

    Article  CAS  PubMed  Google Scholar 

  49. Potkin SG, Phiri P, Szegedi A, et al. Long-term effects of asenapine or olanzapine in patients with persistent negative symptoms of schizophrenia: a pooled analysis. Schizophr Res. 2013;150(2–3):442–9.

    Article  PubMed  Google Scholar 

  50. Gao K, Mackle M, Cazorla P, et al. Comparison of somnolence associated with asenapine, olanzapine, risperidone, and haloperidol relative to placebo in patients with schizophrenia or bipolar disorder. Neuropsychiatr Dis Treat. 2013;9:1145–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Chapel S, Hutmacher MM, Haig G, et al. Exposure-response analysis in patients with schizophrenia to assess the effect of asenapine on QTc prolongation. J Clin Pharmacol. 2009;49:1297–308.

    Article  CAS  PubMed  Google Scholar 

  52. Chapel S, Hutmacher MM, Bockbrader H, et al. Comparison of QTc data analysis methods recommended by the ICH E14 guidance and exposure-response analysis: case study of a thorough QT study of asenapine. Clin Pharmacol Ther. 2011;89(1):75–80.

    Article  CAS  PubMed  Google Scholar 

  53. Thomas JE, Caballero J, Harrington CA. The incidence of akathisia in the treatment of schizophrenia with aripiprazole, asenapine and lurasidone: a meta-analysis. Curr Neuropharmacol. 2015;13(5):681–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kemp DE, Zhao J, Cazorla P, et al. Weight change and metabolic effects of asenapine in patients with schizophrenia and bipolar disorder. J Clin Psychiatry. 2014;75(3):238–45.

    Article  CAS  PubMed  Google Scholar 

  55. Cazorla P, Mackle M, Zhao J, et al. Safety and tolerability of switching to asenapine from other antipsychotic agents: pooled results from two randomized multicenter trials in stable patients with persistent negative symptoms in schizophrenia. Neuropsychiatr Dis Treat. 2012;8:247–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. De Hert M, Guiraud-Diawara A, Marre C. Comparison of metabolic syndrome incidence among schizophrenia patients treated with asenapine versus olanzapine [abstract no. 2584]. Eur Psychiatry. 2013;28(Suppl 1).

  57. Meiji Seika Pharma. Sycrest® sublingual tablets 5 and 10 mg: Japanese prescribing information. 2016. http://www.meiji-seika-pharma.co.jp/medical/product/sycrest/pdf/sycrest_ATC.pdf. Accessed 13 Jun 2016.

  58. National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: treatment and management (NICE clinical guideline 178). 2014. https://www.nice.org.uk/guidance/cg178. Accessed 13 Jun 2016.

  59. Lehman AF, Lieberman JA, Dixon LB, et al. American Psychiatric Association practice guideline for the treatment of patients with schizophrenia, 2nd edn. 2004. http://psychiatryonline.org. Accessed 13 Jun 2016.

  60. Dixon L, Perkins D, Calmes C. American Psychiatric Association guideline watch (September 2009): practice guideline for the treatment of patients with schizophrenia. 2009. http://psychiatryonline.org. Accessed 13 Jun 2016.

Download references

Acknowledgments

During the peer review process, the manufacturer of asenapine was offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand

    Greg L. Plosker & Emma D. Deeks

Authors
  1. Greg L. Plosker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emma D. Deeks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emma D. Deeks.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Greg Plosker and Emma Deeks are salaried employees of Adis/Springer, are responsible for the article content and declare no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: K. Gao, Department of Psychiatry, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA; and S. Rej, Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Plosker, G.L., Deeks, E.D. Asenapine: A Review in Schizophrenia. CNS Drugs 30, 655–666 (2016). https://doi.org/10.1007/s40263-016-0363-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40263-016-0363-2

Keywords

Search

Navigation