OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Asenapine – Saphris®, Secuado®

DRUG CLASS

Antipsychotic Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

View in own window

DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Asenapine	65576-45-6	C17-H16-Cl-N-O

ANNOTATED BIBLIOGRAPHY

References updated: 05 June 2023

• Meyer JM. Pharmacotherapy of psychosis and mania. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 279-302.

  (Textbook of pharmacology and therapeutics).
• Larry D. Hepatotoxicity of psychotropic drugs and drugs of abuse. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 2nd ed. New York: Informa Healthcare USA, 2007, pp. 507-26.

  (Review of hepatotoxicity of psychiatric agents, does not discuss asenapine).
• Potkin SG, Cohen M, Panagides J. Efficacy and tolerability of asenapine in acute schizophrenia: a placebo- and risperidone-controlled trial. J Clin Psychiatry. 2007;68:1492–500. [PubMed: 17960962]

  (Among 174 patients with acute schizophrenia treated with sublingual asenapine [5 mg] or risperidone [3 mg] or placebo twice daily for 6 weeks, symptom scores improved more with asenapine and risperidone than with placebo, although adverse event rates were similar; no mention of ALT elevations or hepatotoxicity).
• Parsons B, Allison DB, Loebel A, Williams K, Giller E, Romano S, Siu C. Weight effects associated with antipsychotics: a comprehensive database analysis. Schizophr Res. 2009;110:103–10. [PubMed: 19321312]

  (Analysis of weight gain in 21 placebo controlled trials [~3300 patients]; average monthly weight gain in pounds was +0.1 with placebo, +0.8 olanzapine, 0.6 risperidone, -0.3 ziprasidone; a 5% increase in weight occurred after one year in 13% of placebo, 39% haloperidol, 20% ziprasidone, 45% risperidone and 60% olanzapine treated subjects; no mention of asenapine).
• McIntyre RS, Cohen M, Zhao J, Alphs L, Macek TA, Panagides J. A 3-week, randomized, placebo-controlled trial of asenapine in the treatment of acute mania in bipolar mania and mixed states. Bipolar Disord. 2009;11:673–86. [PubMed: 19839993]

  (Among 480 adults with an acute manic or mixed episode in a prospective controlled trial for 3 weeks, there was rapid improvement in symptoms with sublingual asenapine [5 mg] and oral olanzapine [3 mg] compared to placebo twice daily; ALT levels increase by 12 U/L on average with asenapine, 33 U/L with olanzapine, but decrease by 7 U/L with placebo, although none of the changes were considered “clinically relevant”).
• McIntyre RS, Cohen M, Zhao J, Alphs L, Macek TA, Panagides J. Asenapine in the treatment of acute mania in bipolar I disorder: a randomized, double-blind, placebo-controlled trial. J Affect Disord. 2010;122(1-2):27–38. [PubMed: 20096936]

  (Among 488 adults with acute mania and bipolar 1 disorder treated with asenapine, olanzapine or placebo for 3 weeks, symptoms score improved more in the asenapine than placebo recipients and “mean changes from baseline in laboratory values…were not clinically significant”).
• Asenapine (Saphris) sublingual tablets for schizophrenia and bipolar disorder. Med Lett Drugs Ther. 2010;52:9–10. [PubMed: 20216523]

  (Concise review of the mechanism of action, pharmacology, efficacy, safety and costs of asenapine as therapy of schizophrenia and bipolar disorder shortly after its approval for use in the US, mentions side effects of akathisia, oral hypoesthesia, somnolence, dizziness and weight gain; no mention of ALT elevations or hepatotoxicity).
• Potkin SG. Asenapine: a clinical overview. J Clin Psychiatry. 2011;72 Suppl 1:14–8. [PubMed: 22217438]

  (Review and overview of the pharmacology, clinical efficacy and safety of sublingual asenapine for treatment of schizophrenia and acute mania mentions occasional hypersensitivity reactions and problems of weight gain with long term therapy; no mention of ALT elevations or hepatotoxicity).
• Asenapine: a less effective, yet more dangerous neuroleptic! Prescrire Int. 2012;21:229–32. [PubMed: 23185842]

  (Short commentary on use of asenapine in bipolar disorders mentions that asenapine has more adverse side effects than other neuroleptics, and these include oral hypoesthesia and hypersensitivity reactions that can be severe).
• Cazorla P, Mackle M, Zhao J, Ha X, Szegedi A. 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. [PMC free article: PMC3383320] [PubMed: 22745558]

  (Among 949 adults with schizophrenia who were switched from standard antipsychotic agents to asenapine or olanzapine in two 26-week controlled trials, common side effects in the first month included somnolence [10% vs 13%], insomnia [17% vs 12%], and headache [14% vs 10%], while serious adverse events occurred in 12% on asenapine and 6% on olanzapine, although no specifics given or mention made of ALT elevations).
• Schoemaker J, Stet L, Vrijland P, Naber D, Panagides J, Emsley R. Long-term efficacy and safety of asenapine or olanzapine in patients with schizophrenia or schizoaffective disorder: an extension study. Pharmacopsychiatry. 2012;45:196–203. [PubMed: 22454251]

  (Among 440 patients with schizophrenia or schizoaffective disorder who were continued on asenapine or olanzapine after a 52 week controlled trial, adverse events were common, but less frequent than during the initial year of treatment, and there were “no major changes in laboratory variables including … liver enzymes”).
• Potkin SG, Phiri P, Szegedi A, Zhao J, Alphs L, Cazorla P. Long-term effects of asenapine or olanzapine in patients with persistent negative symptoms of schizophrenia: a pooled analysis. Schizophr Res. 2013;150:442–9. [PubMed: 24075603]

  (Among 502 patients with schizophrenia treated with asenapine or olanzapine in two clinical trials for 26 weeks with another 26 week extension study, adverse events were not discussed in detail and no mention made of ALT elevations or hepatotoxicity).
• Drugs for psychiatric disorders. Treat Guidel Med Lett. 2013;11(130):53–64. [PubMed: 23715100]

  (Concise review of safety, efficacy and role of drugs for psychiatric disorders mentions that asenapine is a second generation antipsychotic agent whose adverse side effects include insomnia, somnolence, nausea, vomiting and weight gain; no mention of ALT elevations or hepatotoxicity).
• Kemp DE, Zhao J, Cazorla P, Landbloom RP, Mackle M, Snow-Adami L, Szegedi A. Weight change and metabolic effects of asenapine in patients with schizophrenia and bipolar disorder. J Clin Psychiatry. 2014;75:238–45. [PubMed: 24499969]

  (Among 1748 patients with schizophrenia or bipolar illness treated in 17 clinical trials, post hoc analyses of weight change showed greater gain with asenapine than placebo during the initial 4 week period [1.2 vs 0.4 kg], but less than with olanzapine [0.9 vs 3.0 kg]; no mention of changes of ALT levels with weight gain).
• Musil R, Obermeier M, Russ P, Hamerle M. Weight gain and antipsychotics: a drug safety review. Expert Opin Drug Saf. 2015;14:73–96. [PubMed: 25400109]

  (Extensive systematic review of the literature on the problem of weight gain during therapy with antipsychotic agents mentions that asenapine has been linked to weight gain and increase in body weight of 7% or more occurs in 3.7-39.2% of patients).
• Landbloom RL, Mackle M, Wu X, Kelly L, Snow-Adami L, McIntyre RS, Mathews M, et al. Asenapine: Efficacy and safety of 5 and 10 mg bid in a 3-week, randomized, double-blind, placebo-controlled trial in adults with a manic or mixed episode associated with bipolar I disorder. J Affect Disord. 2016;190:103–10. [PubMed: 26496015]

  (Among 367 patients with a manic or mixed episode associated with bipolar 1 disorder treated with asenapine [5 or 10 mg] or placebo twice daily for 3 weeks, symptoms were somewhat more improved with asenapine than placebo, while adverse events were more frequent, particularly somnolence [20% and 26% vs 4%] and oral hypoesthesia [16% and 29% vs 2%], although “no patients had elevated liver enzymes that met criteria for potential drug-induced liver injury”).
• Findling RL, Landbloom RP, Mackle M, Pallozzi W, Braat S, Hundt C, Wamboldt MZ, et al. Safety and efficacy from an 8 week double-blind trial and a 26 week open-label extension of asenapine in adolescents with schizophrenia. J Child Adolesc Psychopharmacol. 2015;25:384–96. [PMC free article: PMC4491161] [PubMed: 26091193]

  (Among 306 adolescents with schizophrenia treated with asenapine [2.5 or 5 mg] or placebo twice daily for 8 weeks, some symptom scores improved with the higher dose of asenapine compared to placebo, but adverse events were also more common including akathisia, dizziness, oral hypoesthesia, insomnia and weight gain; no mention of ALT elevations or hepatotoxicity).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterology. 2015;148:1340–52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 patients with drug induced liver injury seen over a ten year period at 8 US medical centers, one case was attributed to olanzapine, but none to asenapine or other atypical antipsychotic medications).
• Schultz K, Wang L, Barr A, Vila Rodriguez F. A case of pseudo-Stauffer's syndrome related to asenapine use. Schizophr Res. 2015;169:500–1. [PubMed: 26549631]

  (50 year old man developed abnormal liver tests 24 days after starting asenapine [bilirubin and ALT not given; Alk P 508 U/L, GGT 904 U/L], which persisted despite stopping valproate and then resolved within a month of stopping asenapine).
• Findling RL, Landbloom RL, Mackle M, Wu X, Snow-Adami L, Chang K, Durgam S. Long-term safety of asenapine in pediatric patients diagnosed with bipolar I disorder: A 50-week open-label, flexible-dose trial. Paediatr Drugs. 2016;18:367–78. [PMC free article: PMC5018262] [PubMed: 27461426]

  (Among 321 pediatric patients [ages 10 to 17 years] with bipolar disorder were treated with sublingual asenapine for up to one year, side effects were generally mild but led to early discontinuation in 15% of patients; no mention of ALT elevations or hepatotoxicity).
• Ketter TA, Durgam S, Landbloom R, Mackle M, Wu X, Mathews M. Long-term safety and tolerability of asenapine: A double-blind, uncontrolled, long-term extension trial in adults with an acute manic or mixed episode associated with bipolar I disorder. J Affect Disord. 2017;207:384–92. [PubMed: 27755982]

  (Among 164 adults with bilar disorder enrolled in a 26 week extension study after a placebo controlled 3 week trial of asenapine, adverse events were mostly neuropsychiatric and weight gain; no mention of ALT elevations or hepatotoxicity).
• Szegedi A, Durgam S, Mackle M, Yu SY, Wu X, Mathews M, Landbloom RP. Randomized, double-blind, placebo-controlled trial of asenapine maintenance therapy in adults with an acute manic or mixed episode associated with bipolar I disorder. Am J Psychiatry. 2018;175:71–79. [PubMed: 28946761]

  (Among 253 patients with acute manic or mixed episodes treated with asenapine [10 mg twice daily] for 12-16 weeks and if they responded were then continued therapy or were switched to placebo, recurrence of manic, mixed, or depressive episodes were less frequent with continuing sublingual asenapine than switching to placebo, and adverse event rates were similar; no mention of ALT elevations or hepatotoxicity).
• Citrome L, Walling DP, Zeni CM, Starling BR, Terahara T, Kuriki M, Park AS, et al. Efficacy and safety of HP-3070, an asenapine transdermal system, in patients with schizophrenia: a phase 3, randomized, placebo-controlled study. J Clin Psychiatry. 2020;82:20m13602. [PubMed: 33326711]

  (Among 614 patients with an acute exacerbation of schizophrenia treated with transdermal asenapine [3.8 or 7.6 mg/24 hours] or placebo for 6 weeks, symptom scores improved more with both doses of asenapine compared with placebo and adverse event rates were similar with no serious adverse events; no mention of ALT elevations or hepatotoxicity).
• In brief: An asenapine patch (Secuado) for schizophrenia. Med Lett Drugs Ther. 2021;63(1615):7–8. [PubMed: 33647000]

  (Concise review of the mechanism of action, clinical efficacy, toxicity and cost of transdermal asenapine shortly after its approval as therapy of schizophrenia in the US; no mention of ALT elevations or hepatotoxicity).
• Zeiss R, Hafner S, Schönfeldt-Lecuona C, Connemann BJ, Gahr M. Drug-associated liver injury related to antipsychotics: exploratory analysis of pharmacovigilance data. J Clin Psychopharmacol. 2022;42:440–444. [PubMed: 35730552]

  (Review of the VigiBase data base of individual case safety reports on antipsychotics and liver injury found positive hepatic safety signals for olanzapine and clozapine but none for risperidone, quetiapine, ziprasidone, asenapine, aripiprazole, brexpiprazole, and cariprazine).