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CNS Drugs

, Volume 23, Issue 9, pp 781–792 | Cite as

Asenapine

  • Juliane Weber
  • Paul L. McCormack
Adis Drug Profile

Abstract

  • ▴ Asenapine is a novel psychopharmacological agent that binds with high affinity and specificity to numerous dopamine, serotonin, noradrenaline (norepinephrine) and histamine receptor subtypes. It is being developed for the treatment of schizophrenia and bipolar mania.

  • ▴ In two randomized, controlled trials of asenapine monotherapy and in one randomized, controlled trial of adjunctive asenapine therapy in adult patients with bipolar I disorder, sublingual asenapine produced significantly greater reductions from baseline than placebo in clinician-assessed Young Mania Rating Scale (YMRS) total score at 3 weeks.

  • ▴ In two randomized, controlled trials in adult patients with acute schizophrenia, treatment with asenapine reduced from baseline the clinician-assessed Positive and Negative Syndrome Scale (PANSS) total score to a significantly greater extent than placebo at 6 weeks.

  • ▴ In schizophrenic patients with predominant, persistent, negative symptoms, asenapine at 26 weeks reduced the Negative Symptom Assessment (NSA-16) total score from baseline to an extent similar to that observed with olanzapine.

  • ▴ Sublingual asenapine was generally well tolerated in clinical trials, with most treatment-emergent adverse events being of mild to moderate severity. Incidence rates of clinically significant weight gain, extrapyramidal symptoms, hyperprolactinaemia and alterations in glucose or lipid metabolism were generally low.

Keywords

Risperidone Olanzapine Last Observation Carry Forward Asenapine Young Mania Rate Scale 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements and Disclosures

This manuscript was reviewed by: R. Ghanbari, University of Ottawa Institute of Mental Health Research, Ottawa, Ontario, Canada; F.I. Tarazi, Harvard Medical School, Department of Psychiatry and Neuroscience Program, McLean Division of Massachusetts General Hospital, Belmont, Massachusetts, USA.

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

References

  1. 1.
    Ayuso-Mateos JL. Global burden of bipolar disorder in the year 2000 [online]. Available from URL: http://www.who.int/healthinfo/statistics/bod_bipolar.pdf [Accessed 2009 Mar 9]
  2. 2.
    Ayuso-Mateos JL. Global burden of schizophrenia in the year 2000: version 1 estimates [online]. Available from URL: http://www.who.int/healthinfo/statistics/bod_schizophrenia.pdf [Accessed 2009 Mar 9]
  3. 3.
    Schering-Plough Corporation. US FDA issues complete response letter for Saphris™ (asenapine) in the acute treatment of both schizophrenia and bipolar I disorder [media release]. 2009 Jan 14Google Scholar
  4. 4.
    Freedman R. The choice of antipsychotic drugs for schizophrenia. N Engl J Med 2005 Sep 22; 353(12): 1286–8PubMedCrossRefGoogle Scholar
  5. 5.
    Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005 Sep 22; 353(12): 1209–23PubMedCrossRefGoogle Scholar
  6. 6.
    Horacek J, Bubenikova-Valesova V, Kopecek M, et al. Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia. CNS Drugs 2006; 20(5): 389–409PubMedCrossRefGoogle Scholar
  7. 7.
    Revicki DA, Matza LS, Flood E, et al. Bipolar disorder and health-related quality of life: review of burden of disease and clinical trials. Pharmacoeconomics 2005; 23(6): 583–94PubMedCrossRefGoogle Scholar
  8. 8.
    Awad AG, Voruganti LNP. The burden of schizophrenia on caregivers: a review. Pharmacoeconomics 2008; 26(2): 149–62PubMedCrossRefGoogle Scholar
  9. 9.
    Shahid M, Walker GB, Zorn SH, et al. Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol 2009 Jan; 23(1): 65–73PubMedCrossRefGoogle Scholar
  10. 10.
    Tarazi FI, Moran-Gates T, Wong EH, et al. Asenapine induces differential regional effects on serotonin receptor subtypes. J Psychopharmacol. Epub 2008 Aug 21Google Scholar
  11. 11.
    Huang M, Li Z, Dai J, et al. Asenapine increases dopamine, norepinephrine, and acetylcholine efflux in the rat medial prefrontal cortex and hippocampus. Neuropsychopharmacology 2008 Nov; 33(12): 2934–45PubMedCrossRefGoogle Scholar
  12. 12.
    Tarazi FI, Moran-Gates T, Wong EH, et al. Differential regional and dose-related effects of asenapine on dopamine receptor subtypes. Psychopharmacology (Berl) 2008 May; 198(1): 103–11CrossRefGoogle Scholar
  13. 13.
    Franberg O, Wiker C, Marcus MM, et al. Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia. Psychopharmacology (Berl) 2008 Feb; 196(3): 417–29CrossRefGoogle Scholar
  14. 14.
    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 (Berl) 1997 Jun 11; 131: 339–45CrossRefGoogle Scholar
  15. 15.
    Ghanbari R, El Mansari M, Shahid M, et al. Electrophysiological characterization of the effects of asenapine at 5-HT1A, 5-HT2A, α2-adrenergic and D2 receptors in the rat brain. Eur Neuropsychopharmacol 2009 Mar; 19(3): 177–87PubMedCrossRefGoogle Scholar
  16. 16.
    Franberg O, Marcus MM, Ivanov V, et al. Asenapine elevates cortical dopamine, noradrenaline and serotonin release: evidence for activation of cortical and subcortical dopamine systems by different mechanisms. Psychopharmacology (Berl) 2009 Jun; 204(2): 251–64CrossRefGoogle Scholar
  17. 17.
    Bishara D, Taylor D. Upcoming agents for the treatment of schizophrenia: mechanism of action, efficacy and tolerability. Drugs 2008; 68(16): 2269–92PubMedCrossRefGoogle Scholar
  18. 18.
    Potkin SG, Alva G, Panagides J, et al. Predicting clinical antipsychotic doses from preclinical and PET studies: a case study with asenapine [abstract plus poster]. American College of Neuropsychopharmacology 42nd Annual Meeting; 2003 Dec 7–11; Puerto RicoGoogle Scholar
  19. 19.
    Henry B, Grimwood S, de Greef HJMM, et al. Asenapine: a translational analysis of receptor occupancy in human and rat brain with therapeutic implications [abstract no. NR5-030]. 161st Annual Meeting of the American Psychiatric Association; 2008 May 3–8; Washington, DCGoogle Scholar
  20. 20.
    Sumner BEH, Shahid M, Tarazi FI, et al. Asenapine displays distinctive induction patterns of c-fos mRNA expression in rat forebrain regions. Neuropsychopharmacology 2006 Dec; 31 Suppl. 1: 196–7Google Scholar
  21. 21.
    Tarazi FI, Choi YK, Gardner M, et al. Asenapine exerts distinctive regional effects on ionotropic glutamate receptor subtypes in rat brain. Synapse 2009 May; 63(5): 413–20PubMedCrossRefGoogle Scholar
  22. 22.
    Gerrits M, Doorstam DP, Spaans E, et al. Effect of valproate on the glucuronidation of asenapine [abstract no. PI-68]. Clin Pharmacol Ther 2008 Mar; 83Suppl. 1: S29Google Scholar
  23. 23.
    Dogterom P, Schnabel PG, Timmer C, et al. Effect of carbamazepine on asenapine pharmacokinetics [abstract no. PII-44]. Clin Pharmacol Ther 2008 Mar; 83Suppl. 1: S55Google Scholar
  24. 24.
    Hulskotte E, Spaans E, Timmer C, et al. Effects of water intake and smoking on the absorption of sublingually administered asenapine [abstract no. NR1-040]. 162nd Annual Meeting of the American Psychiatric Association; 2009 May 16–21; San Francisco (CA)Google Scholar
  25. 25.
    Dogterom P, Hulskotte E, Gerrits M, et al. Asenapine pharmacokinetics: influence of cytochrome p450 modulators and udp-glucuronyltransferase inhibition [abstract no. P.3.d.008]. Eur Neuropsychopharmacol 2008 Oct; 18Suppl. 4: S452–3CrossRefGoogle Scholar
  26. 26.
    Peeters P, Bockbrader H, Spaans E, et al. Asenapine pharmacokinetics: influence of hepatic and renal impairment [abstract no. NR4-081]. 161st Annual Meeting of the American Psychiatric Association; 2008 May 3–8; Washington, DCGoogle Scholar
  27. 27.
    Calabrese JR, Cohen M, Zhao J, et al. Efficacy and safety of asenapine adjunctive treatment for acute mania associated with bipolar disorder [abstract no. NR3-061]. 161st Annual Meeting of the American Psychiatric Association; 2008 May 3–8; Washington, DCGoogle Scholar
  28. 28.
    Panagides J, McIntyre RS, Alphs L, et al. Asenapine in acute mania: a randomized, double-blind, placebo- and olanzapine-controlled trial (ARES 7501004) [abstract no. 720]. Biol Psychiatry 2007 Apr 15; 61 Suppl. 8: 222S-3SGoogle Scholar
  29. 29.
    Hirschfeld RMA, Panagides J, Alphs L, et al. Asenapine in acute mania: a randomized, double-blind, placebo- and olanzapine-controlled trial (ARES 7501005) [abstract no. NR333]. 160th Annual Meeting of the American Psychiatric Association; 2007 May 19–24; San Diego (CA)Google Scholar
  30. 30.
    McIntyre R, Cohen M, Zhao J, et al. Double-blind extension studies of asenapine in patients with bipolar mania [abstract no. NR4-092]. 161st Annual Meeting of the American Psychiatric Association; 2008 May 3–8; Washington, DCGoogle Scholar
  31. 31.
    Potkin SG, Cohen M, Panagides J. Efficacy and tolerability of asenapine in acute schizophrenia: a placebo- and risperidone-controlled trial. J Clin Psychiatry 2007 Oct; 68(10): 1492–500PubMedCrossRefGoogle Scholar
  32. 32.
    Kane JM, Zhao J, Cohen M, et al. Efficacy and safety of asenapine in patients with acute schizophrenia [abstract no. NR4-051]. 161st Annual Meeting of the American Psychiatric Association; 2008 May 3–8; Washington, DCGoogle Scholar
  33. 33.
    Cazorla P, Panagides J, Alphs L, et al. Asenapine versus olanzapine in patients with predominant, persistent negative symptoms of schizophrenia [abstract no. NR4-082]. 161st Annual Meeting of the American Psychiatric Association; 2008 May 3–8; Washington, DCGoogle Scholar
  34. 34.
    Cazorla P, Phiri P, den Hollander W, et al. Long-term treatment with asenapine versus olanzapine in subjects with predominant, persistent negative symptoms of schizophrenia [abstract no. 088]. 47th Annual Meeting of the American College of Neuropsychopharmacology; 2008 Dec7–11;Scottsdale(AZ)Google Scholar
  35. 35.
    Panagides J, McIntyre RS, Alphs L, et al. Asenapine versus olanzapine in acute mania: a double-blind extension study (ARES 7501006) [abstract no. 721]. Biol Psychiatry 2007 Apr 15; 61 Suppl. 8: 223SGoogle Scholar
  36. 36.
    van Willigenburg A, Zhao J, Panagides J. Asenapine effects on individual young mania rating scale items in bipolar disorder patients: a pooled analysis [abstract no. NR4-007]. 161st Annual Meeting of the American Psychiatric Association; 2008 May 3–8; Washington, DCGoogle Scholar
  37. 37.
    Cazorla P, Panagides J, Alphs L, et al. Asenapine versus olanzapine in patients with predominant persistent negative symptoms of schizophrenia [abstract no. P-02.26]. Int J Neuropsychopharmacol 2008 Jul; 11 Suppl. 1: 138–9Google Scholar
  38. 38.
    Alphs L, Panagides J, Lancaster S. Asenapine in the treatment of negative symptoms of schizophrenia: clinical trial design and rationale. Psychopharmacol Bull 2007; 40(2): 41–53PubMedGoogle Scholar
  39. 39.
    ClinicalTrials.gov. 6-Month extension trial of asenapine with olanzapine in negative symptom patients who completed the first 6-month trial (A7501014) (completed) [online]. Available from URL: http://clinicaltrials.gov/ct2/show/NCT00174265?term=asenapine+olanzapine+schizophrenia&rank=3 [Accessed 2009 Aug 2]
  40. 40.
    Emsley RA, Schoemaker JH, Vrijland P, et al. Long-term safety of asenapine versus olanzapine in patients with schizophrenia or schizoaffective disorder [abstract no. 323]. 21st Annual US Psychiatric and Mental Health Congress; 2008 Oct 30–Nov 1; San Diego (CA)Google Scholar
  41. 41.
    Preskorn S, Chapel S, Panagides J. Effect of asenapine versus quetiapine and placebo on QTc interval in patients with schizophrenia [abstract no. P.3.c.050]. Eur Neuropsychopharmacol 2007 Oct; 17Suppl. 4: S453CrossRefGoogle Scholar
  42. 42.
    Potkin SG, Kane JM, Emsley RA, et al. Asenapine in schizophrenia: an overview of clinical trials in the Olympia program [abstract no. 78]. 161st Annual Meeting of the American Psychiatric Association; 2008 May 3–8; Washington, DCGoogle Scholar
  43. 43.
    McIntyre R, Panagides J, Alphs L, et al. Treatment of mania in bipolar I disorder: a placebo- and olanzapine-controlled trial of asenapine (ARES 7501005) [abstract no. P.2.e.012]. Eur Neuropsychopharmacol 2007 Oct; 17Suppl. 4: S383CrossRefGoogle Scholar
  44. 44.
    Schering-Plough Corporation. Schering-Plough announces European filing of Sycrest® (asenapine) for the treatment of schizophrenia and bipolar I disorder [media release]. 2009 Jun 2Google Scholar

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Wolters Kluwer Health ∣ AdisMairangi Bay, North Shore 0754, AucklandNew Zealand

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