Asenapine: A Clinical Review of a Second-Generation Antipsychotic



      Schizophrenia and bipolar disorder are both prevalent types of psychiatric illness in the United States. As second-generation antipsychotics have become a more viable first-line treatment option, their use has been associated with a new era of adverse events (AEs), most notably metabolic and cardiovascular concerns. Although treatment options for schizophrenia and bipolar disorder have arguably improved, there continues to be a need for medications that achieve and maintain desired efficacy with minimal AEs.


      This article serves as a comprehensive review of the pharmacologic profile of the second-generation antipsychotic asenapine, as well as a review of its efficacy and safety profiles based on the findings from clinical trials in schizophrenia and bipolar disorder.


      Searches of Ovid MEDLINE, EMBASE, and IDIS were conducted (January 1996 to November 2011) to identify clinical studies and other primary literature sources with the following search terms: asenapine, bipolar disorder, antipsychotic, psychosis, dopamine, and schizophrenia. Only studies of asenapine and placebo and/or active-comparator arms were included.


      The literature search yielded 67 unique articles, including review articles, which were excluded. The efficacy of asenapine was reported in 3 clinical studies in patients with schizophrenia, 1 each in acute and long-term settings, measured as significant changes in Positive and Negative Syndrome Scale scores over 6 and 52 weeks. Asenapine also had reported efficacy in the prevention of relapse in schizophrenia during a 26-week extension study. In addition, efficacy of asenapine was reported in 2 studies in acute mania as well as extension phases of both 9 and 40 weeks, as determined by significant changes in Young Mania Rating Scale scores. The most commonly reported AEs in these studies were somnolence (13%–24%), extrapyramidal symptoms (EPS) (7%–12%), and dizziness (11%).


      The findings from multiple studies have suggested that asenapine is efficacious in the acute treatment of schizophrenia. Asenapine has reported long-term efficacy for this indication and the potential to reduce the incidence of relapse. Asenapine efficacy was also reported in the treatment of acute manic or mixed states associated with bipolar I disorder. Asenapine had an acceptable safety profile across the different disease states studied, although it was not devoid of metabolic and EPS-related AEs.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Therapeutics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Buckley P.F.
        Treatment of schizophrenia: let's talk dollars and sense [published correction appears in Am J Manag Care. 1998;4:611].
        Am J Manag Care. 1998; 4: 369-383
        • Csernansky J.G.
        • Mahmoud R.
        • Brenner R.
        A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia.
        N Engl J Med. 2002; 346: 16-22
        • Rosenheck R.
        • Perlick D.
        • Bingham S.
        • Liu-Mares W.
        • et al.
        Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia.
        JAMA. 2003; 290: 2693-2702
        • American Psychiatric Association, Workgroup on Schizophrenia
        Practice guideline for the treatment of patients with schizophrenia, second edition.
        Am J Psychiatry. 2004; 161: 1-47
        • Faglioni A.
        • Chengappa R.
        • Soreca I.
        • Chang J.
        Bipolar disorder and the metabolic syndrome: causal factors, psychiatric outcomes and economic burden.
        CNS Drugs. 2008; 22: 655-669
        • Kessler R.C.
        • Berglund P.
        • Demler O.
        • et al.
        Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication.
        Arch Gen Psychiatry. 2005; 62: 593-602
        • Hirschfeld R.M.
        • Calabrese J.R.
        • Weissman M.M.
        • et al.
        Screening for bipolar disorder in the community.
        J Clin Psychiatry. 2003; 64: 53-59
        • Merikangas K.R.
        • Akiskal H.S.
        • Angst J.
        • et al.
        Lifetime and 12-month prevalence of bipolar spectrum disorder in the national comorbidity survey replication.
        Arch Gen Psychiatry. 2007; 64: 543-552
        • American Psychiatric Association, Workgroup on Bipolar Disorder
        Practice guideline for the treatment of patients with bipolar disorder (revision).
        Am J Psychiatry. 2002; 159: 1-39
        • Lieberman J.A.
        • Stroup T.S.
        • McEvoy J.P.
        • et al.
        Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.
        N Engl J Med. 2005; 353: 1209-1223
        • Jones P.B.
        • Barnes T.R.E.
        • Davies L.
        • et al.
        Randomized controlled trial of the effect on quality of life of second vs. first generation antipsychotic drugs in schizophrenia.
        Arch Gen Psychiatry. 2006; 63: 1079-1087
      1. Clozaril (colazapine) [package insert].
        Novartis Pharmaceutical Corp, East Hanover, NJ2010
      2. Risperdal (risperidone) [package insert].
        Ortho-McNeil-Janssen Pharmaceuticals, Titusville, NJ2011
      3. Zyprexa (olanzapine) [package insert].
        Eli Lilly and Co, Indianapolis, Ind.2010
      4. Seroquel and Seroquel XR (quetiapine) [package insert].
        AstraZeneca Pharmaceuticals, Wilmington, Del.2011
      5. Geodon (ziprasidone) [package insert].
        Pfizer Inc, New York, NY2010
      6. Abilify (aripiprazole) [package insert].
        Otsuka Pharmaceuticals, Tokyo, Japan2010
      7. Risperdal Consta (risperidone) [package insert].
        Ortho-McNeil-Janssen Pharmaceuticals, Titusville, NJ2010
      8. Invega and Invega Sustenna (paliperidone) [package insert].
        Ortho-McNeil-Janssen Pharmaceuticals, Titusville, NJ2010
      9. Saphris (asenapine) [package insert].
        Merck & Co Inc, Whitehouse Station, NJJanuary 2011
      10. Fanapt (Iloperidone) [package insert].
        Vanda Pharmaceuticals, Rockville, Md.2010
        • US Food and Drug Administration
        Saphris (Asenapine) Sublingual Tablets.
        (Accessed March 2010)
        • Schering-Plough Research Institute
        Saphris (Asenapine) Sublingual Tablets.
        (Accessed March 2010)
        • 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: 1762-1784
        • McIntyre R.S.
        • Cohen M.
        • Zhao J.
        • et al.
        A 3-week, randomized, placebo-controlled trial of asenapine in the treatment of acute mania in bipolar mania and mixed states.
        Bipolar Disorders. 2009; 11: 673-686
        • McIntyre R.S.
        • Cohen M.
        • Zhao J.
        • et al.
        Asenapine in the treatment of acute mania in bipolar I disorder: a randomized, double-blind, placebo-controlled trial.
        J Affect Disord. 2010; 122: 27-38
        • McIntyre R.S.
        • Cohen M.
        • Zhao J.
        • et al.
        Asenapine versus olanzapine in acute mania: a double-bind extended treatment of bipolar mania.
        Bipolar Disorders. 2009; 11: 815-826
        • McIntyre R.S.
        • Cohen M.
        • Zhao J.
        • et al.
        Asenapine for long-term treatment of bipolar disorder: a double-blind 40-week extension study.
        J Affect Disord. 2010; 126: 358-365
        • Potkin S.G.
        • Cohen M.
        • Panagides J.
        Efficacy and tolerability of asenapine in acute schizophrenia: a placebo- and risperidone-controlled trial.
        J Clin Psychiatry. 2007; 68: 1492-1500
        • Schoemaker J.
        • Naber D.
        • Vrijland P.
        • et al.
        Long-term assessment of asenapine vs. olanzapine in patients with schizophrenia or schizoaffective disorder.
        Pharmacopsychiatry. 2010; 43: 138-146
        • Kane J.M.
        • 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: 349-355
        • Hussar D.
        • Abbas C.
        New drugs: asenapine, iloperidone, and bepotastine besilate.
        J Am Pharm Assoc. 2010; 50: 107-110
        • Shahid M.
        • Walker G.B.
        • Zorn S.H.
        • et al.
        Asenapine: a novel psychopharmacologic agent with a unique human receptor signature.
        J Psychopharmacol. 2009; 2391: 65-73
        • Franberg O.
        • Marcus M.M.
        • Ivanov V.
        • et al.
        Asenapine elevates cortical dopamine, noradrenaline, and serotonin release.
        Psychopharmacology. 2009; 204: 251-264
        • Ghanbari R.
        • El Mansari M.
        • Shahid M.
        • Blier P.
        Electrophysiological characterization of the effects of asenapine at 5-HT1A, 5-HT2A, alpha-2 adrenergic and D2 receptors in the rat brain.
        European Neuropsychopharmacology. 2009; 19: 177-187
        • Tarazi F.I.
        • Moran-Gates T.
        • Wong E.H.F.
        • Shahid M.
        Differential regional and dose-related effects of asenapine on dopamine receptor subtypes.
        Psychopharmacology. 2008; 198: 103-111
        • Franberg O.
        • Wiker C.
        • Marcus M.M.
        • et al.
        Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia.
        Psychopharmacology. 2008; 196: 417-429
        • van de Wetering-Krebbers S.F.M.
        • Jacobs P.L.
        • Kemperman G.J.
        • et al.
        Metabolism and excretion of asenapine in healthy male subjects.
        Drug Metab Disposition. 2011; 39: 580-590
        • Weber J.
        • McCormack P.L.
        CNS Drugs. 2009; 23: 781-792
        • Shahid M.
        • Walker G.B.
        • Zorn S.H.
        • et al.
        Asenapine: a novel psychopharmacologic agent with a unique human receptor signature.
        J Psychopharmacol. 2009; 23: 65-73
        • Tarazi F.I.
        • Kee Choi Y.
        • Gardner M.
        • et al.
        Asenapine exerts distinctive regional effects on inotropic glutamate receptor subtypes in rat brain.
        Synapse. 2009; 63: 413-420
        • Den Boer J.
        • Korf J.
        Dopamine receptor subtypes and schizophrenia: a clinical perspective.
        in: Ellenbroek B.A. Cools A.R. Atypical Antipsychotics. Birkhäuser Verlag, Basel, Switzerland2000: 163-190
        • Dogterom P.
        • Hulskotte E.
        • Gerrits M.
        • et al.
        Asenapine pharmacokinetics: influence of cytochrome P450 modulators and UDP-glucuronyltransferase inhibition.
        Eur Neuropsychopharmacol. 2008; 18 (Abstract P.3.d008): S4452-S4453
        • Peeters P.
        • Bockbrader H.
        • Spaans E.
        • et al.
        Asenapine pharmacokinetics in hepatic and renal impairment.
        Clin Pharmacokinet. 2011; 50: 471-481