Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-22T08:24:23.177Z Has data issue: false hasContentIssue false
  • English
  • Français

Oral Antipsychotic Update: A Brief Review of New and Investigational Agents for the Treatment of Schizophrenia

Published online by Cambridge University Press:  10 December 2012

Leslie Citrome
Leslie Citrome*
Affiliation:
Clinical Professor of Psychiatry & Behavioral Sciences, New York Medical College, Valhalla, NY
*
Address correspondence to: Leslie Citrome, 11 Medical Park Drive, Suite 106, Pomona, NY 10970, USA. (Email [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

This narrative review provides an overview of the three new oral second-generation antipsychotics that have become available in the US: iloperidone, asenapine and lurasidone. Although they are associated with less weight gain and fewer metabolic abnormalities than some of the older second-generation antipsychotics, iloperidone, asenapine and lurasidone have differences that make them unique from each other. Examples of these differences include dosing frequency, specific instructions on dosing with food, titration requirements, and potential association with sedation, extrapyramidal side effects, akathisia, and prolongation of the ECG QT interval. Additional information is provided regarding agents in late stage clinical development for the treatment of schizophrenia: cariprazine and brexpiprazole (both are dopamine D2 receptor partial agonists) and bitopertin (a glycine transport inhibitor that may have antipsychotic effects).

Keywords

antipsychoticasenapinebitopertinbrexpiprazolecariprazineiloperidonelurasidoneschizophrenia
Type
CME Article
Information
CNS Spectrums , Volume 17 , Issue s1: CME SUPPLEMENT: Optimizing Care for Patients with Schizophrenia , November 2012 , pp. 1 - 9
Copyright
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Volavka, J, Citrome, L. Oral antipsychotics for the treatment of schizophrenia: heterogeneity in efficacy and tolerability should drive decision-making. Expert Opin Pharmacother. 2009; 10(12): 1917–1928.CrossRefGoogle ScholarPubMed
2.Ballaz, SJ, Akil, H, Watson, SJ. The 5-HT7 receptor: role in novel object discrimination and relation to novelty-seeking behavior. Neuroscience. 2007; 149(1): 192–202.CrossRefGoogle Scholar
3.Shayegan, DK, Stahl, SM. Atypical antipsychotics: matching receptor profile to individual patient's clinical profile. CNS Spectr. 2004; 9(Suppl. 11): 6–14.CrossRefGoogle ScholarPubMed
4.Potkin, SG, Litman, RE, Torres, R, Wolfgang, CD. Efficacy of iloperidone in the treatment of schizophrenia: initial phase 3 studies. J Clin Psychopharmacol. 2008; 28(2 Suppl 1): S4–S11.CrossRefGoogle ScholarPubMed
5.Cutler, AJ, Kalali, AH, Weiden, PJ, Hamilton, J, Wolfgang, CD. Four-week, double-blind, placebo- and ziprasidone-controlled trial of iloperidone in patients with acute exacerbations of schizophrenia. J Clin Psychopharmacol. 2008; 28(2 Suppl 1): S20–S28.CrossRefGoogle ScholarPubMed
6.Citrome, L. Iloperidone for schizophrenia: a review of the efficacy and safety profile for this newly commercialised second-generation antipsychotic. Int J Clin Pract. 2009; 63(8): 1237–1248.CrossRefGoogle ScholarPubMed
7.Citrome, L. Iloperidone redux: a dissection of the Drug Approval Package for this newly commercialised second-generation antipsychotic. Int J Clin Pract. 2010; 64(6): 707–718.CrossRefGoogle ScholarPubMed
8.Citrome, L, Meng, X, Hochfeld, M, Stahl, SM. Efficacy of iloperidone in the short-term treatment of schizophrenia: a post hoc analysis of pooled patient data from four phase III, placebo- and active-controlled trials. Hum Psychopharmacol. 2012; 27(1): 24–32.CrossRefGoogle ScholarPubMed
9.Citrome, L, Meng, X, Hochfeld, M. Efficacy of iloperidone in schizophrenia: a PANSS five-factor analysis. Schizophr Res. 2011; 131(1–3): 75–81.CrossRefGoogle ScholarPubMed
10.Kane, JM, Lauriello, J, Laska, E, Di Marino, M, Wolfgang, CD. Long-term efficacy and safety of iloperidone: results from 3 clinical trials for the treatment of schizophrenia. J Clin Psychopharmacol. 2008; 28(2 Suppl 1): S29–S35.CrossRefGoogle ScholarPubMed
11. Novartis. Fanapt (iloperidone) tablets. Product label, revised January 2012. http://www.pharma.us.novartis.com/product/pi/pdf/fanapt.pdf (accessed 19 July 2012).Google Scholar
12. AstraZeneca. Seroquel XR (quetiapine fumarate extended release). Product label, revised December 2011. http://www1.astrazeneca-us.com/pi/seroquelxr.pdf (accessed 19 July 2012).Google Scholar
13. AstraZeneca. Seroquel (quetiapine fumarate). Product label, revised December 2011. http://www1.astrazeneca-us.com/pi/seroquel.pdf (accessed 19 July 2012).Google Scholar
14.Marek, GJ, Aghajanian, GK. 5-HT2A receptor or alpha1-adrenoceptor activation induces excitatory postsynaptic currents in layer V pyramidal cells of the medial prefrontal cortex. Eur J Pharmacol. 1999; 367(2–3): 197–206.CrossRefGoogle ScholarPubMed
15.Stahl, SM. Stahl's Essential Psychopharmacology, 4th Edition, Cambridge University Press, Cambridge UK, February 2013 (in press).Google Scholar
16. Merck. Saphris (asenapine). Product label, revised May 2012. http://www.spfiles.com/pisaphrisv1.pdf (accessed 19 July 2012).Google Scholar
17.Kane, JM, Cohen, M, Zhao, J, Alphs, L, Panagides, J. 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): 106–115.CrossRefGoogle Scholar
18.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): 1492–1500.CrossRefGoogle ScholarPubMed
19.Kane, JM, Mackle, M, Snow-Adami, L, Zhao, J, Szegedi, A, Panagides, J. A randomized placebo-controlled trial of asenapine for the prevention of relapse of schizophrenia after long-term treatment. J Clin Psychiatry. 2011; 72(3): 349–355.CrossRefGoogle ScholarPubMed
20.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): 1762–1784.CrossRefGoogle ScholarPubMed
21.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(7): 673–686.CrossRefGoogle ScholarPubMed
22.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.CrossRefGoogle ScholarPubMed
23.Szegedi, A, Calabrese, JR, Stet, L, Mackle, M, Zhao, J, Panagides, J, Apollo Study Group. Asenapine as adjunctive treatment for acute mania associated with bipolar disorder: results of a 12-week core study and 40-week extension. J Clin Psychopharmacol. 2012; 32(1): 46–55.CrossRefGoogle ScholarPubMed
24.Schoemaker, J, Naber, D, Vrijland, P, Panagides, J, Emsley, R. Long-term assessment of asenapine vs. olanzapine in patients with schizophrenia or schizoaffective disorder. Pharmacopsychiatry. 2010; 43(4): 138–146.CrossRefGoogle ScholarPubMed
25.Buchanan, RW, Panagides, J, Zhao, J, etal. Asenapine versus olanzapine in people with persistent negative symptoms of schizophrenia. J Clin Psychopharmacol. 2012; 32(1): 36–45.CrossRefGoogle ScholarPubMed
26.McIntyre, RS, Cohen, M, Zhao, J, Alphs, L, Macek, TA, Panagides, J. Asenapine versus olanzapine in acute mania: a double-blind extension study. Bipolar Disord. 2009; 11(8): 815–826.CrossRefGoogle Scholar
27.McIntyre, RS, Cohen, M, Zhao, J, Alphs, L, Macek, TA, Panagides, J. Asenapine for long-term treatment of bipolar disorder: a double-blind 40-week extension study. J Affect Disord. 2010; 126(3): 358–365.CrossRefGoogle ScholarPubMed
28.Citrome, L. Role of sublingual asenapine in treatment of schizophrenia. Neuropsychiatr Dis Treat. 2011; 7: 325–339.Google ScholarPubMed
29.Nakamura, M, Ogasa, M, Guarino, J, etal.Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-controlled trial. J Clin Psychiatry. 2009; 70(6): 829–836.CrossRefGoogle ScholarPubMed
30.Meltzer, HY, Cucchiaro, J, Silva, R, etal. Lurasidone in the treatment of schizophrenia: a randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry. 2011; 168(9): 957–967.CrossRefGoogle ScholarPubMed
31.Ogasa, M, Kimura, T, Nakamura, M, Guarino, J. Lurasidone in the treatment of schizophrenia: a 6-week, placebo-controlled study. Psychopharmacology (Berl). 2012 Aug 19. [Epub ahead of print].CrossRefGoogle Scholar
32.Citrome, L. Lurasidone for schizophrenia: a review of the efficacy and safety profile for this newly approved second-generation antipsychotic. Int J Clin Pract. 2011; 65(2): 189–210.CrossRefGoogle ScholarPubMed
33. Sunovion. Latuda (lurasidone HCl). Product label, revised April 2012. http://latudahcp.com/LatudaPrescribingInformation.pdf (accessed 19 July 2012).Google Scholar
34.Citrome, L. Lurasidone for the acute treatment of adults with schizophrenia: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? Clin Schizophr Relat Psychoses. 2012; 6(2): 76–85.CrossRefGoogle ScholarPubMed
35.Citrome, L, Cucchiaro, J, Sarma, K, etal. Long-term safety and tolerability of lurasidone in schizophrenia: a 12-month, double-blind, active-controlled study. Int Clin Psychopharmacol. 2012; 27(3): 165–176.CrossRefGoogle ScholarPubMed
36.Loebel, A, Cucchiaro, J, Xu, J, Sarma, K, Pikalov, A, Kane, JM. Effectiveness of lurasidone vs. quetiapine XR for relapse prevention in schizophrenia: a 12-month, double-blind study. Poster Presentation NR6-36, American Psychiatric Association 165th Annual Meeting, May 5–9, 2012, Philadelphia, Pennsylvania.CrossRefGoogle Scholar
37.Citrome, L. Lurasidone in schizophrenia: new information about dosage and place in therapy. Adv Therapy. 2012 Sep 20. [Epub ahead of print].CrossRefGoogle Scholar
38.Loebel, A, Cucchiaro, J, Silva, R, etal. Lurasidone monotherapy for the treatment of bipolar I depression: results of a 6-week, double-blind, placebo-controlled study. Poster Presentation NR4-58, American Psychiatric Association 165th Annual Meeting, May 5–9, 2012, Philadelphia, Pennsylvania.Google Scholar
39.Loebel, A, Cucchiaro, J, Silva, R, etal. Lurasidone adjunctive to lithium or valproate for the treatment of bipolar I depression: results of a 6-week, double-blind, placebo-controlled study. Poster Presentation NR4-29, American Psychiatric Association 165th Annual Meeting, May 5–9, 2012, Philadelphia, Pennsylvania.Google Scholar
40.Citrome, L, Nasrallah, HA. On-label on the table: what the package insert informs us about the tolerability profile of oral atypical antipsychotics, and what it does not. Expert Opin Pharmacother. 2012; 13(11): 1599–1613.CrossRefGoogle ScholarPubMed
41.Citrome, L. Drug safety evaluation of ziprasidone. Expert Opin Drug Saf. 2011; 10(3): 437–448.CrossRefGoogle ScholarPubMed
42.Bose, A, Li, D, Migliore, R, etal. The efficacy and safety of the novel antipsychotic cariprazine in acute exacerbation of schizophrenia. Poster Presentation I-73, NCDEU 50th Annual Meeting, June 14–17, 2010, Boca Raton, Florida.Google Scholar
43.Cutler, A, Bose, A, Durgam, S, etal. Safety and tolerability of cariprazine in the long-term treatment of schizophrenia: results from a 48-week extension study. Poster Presentation NR6-50, American Psychiatric Association 165th Annual Meeting, May 5–9, 2012, Philadelphia, Pennsylvania.Google Scholar
44.Knesevich, MA, Papadakis, K, Bose, A, etal. The efficacy and tolerability of cariprazine in acute mania associated with bipolar disorder: a phase II trial. Poster Presentation NR1-49, American Psychiatric Association 162nd Annual Meeting, May 16–21, 2009, San Francisco, California.Google Scholar
45.Starace, A, Bose, A, Wang, Q, etal. Cariprazine in the treatment of acute mania in bipolar disorder: a double-blind, placebo-controlled, Phase III trial. Poster Presentation NR9-42, American Psychiatric Association 165th Annual Meeting, May 5–9, 2012, Philadelphia, Pennsylvania.Google Scholar
46.McQuade, R, Hobart, M, Forbes, RA, etal. A Phase II trial assessing the efficacy and safety of OPC-34712 in the acute treatment of adult schizophrenia (Study 331-07-203). Poster Presentation 140, 2011 US Psychiatric Congress, November 7–10, 2011.Google Scholar
47.Thase, M, Fava, M, Hobart, M, etal. Efficacy and safety of adjunctive OPC-34712 in major depressive disorder: a Phase II, randomized, placebo-controlled study. Poster Presentation NR4-65, American Psychiatric Association 164th Annual Meeting, May 14–18, 2011, Honolulu, Hawaii.Google Scholar
48.Kantrowitz, J, Javitt, DC. Glutamatergic transmission in schizophrenia: from basic research to clinical practice. Curr Opin Psychiatry. 2012; 25(2): 96–102.CrossRefGoogle ScholarPubMed
49.Umbricht, D, Yoo, K, Youssef, E, etal. Investigational glycine transporter type 1 (GlyT1) inhibitor RG1678: results of the proof-of-concept study for the treatment of negative symptoms in schizophrenia. Poster Presentation 49, ACNP 49th Annual Meeting, December 5–9, 2010, Miami Beach, Florida.Google Scholar
50.Kinon, BJ, Gómez, JC. Clinical development of pomaglumetad methionil: A non-dopaminergic treatment for schizophrenia. Neuropharmacology. 2012 Jun 18. [Epub ahead of print]Google ScholarPubMed
51.Patil, ST, Zhang, L, Martenyi, F, etal. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nat Med. 2007; 13(9): 1102–1107.CrossRefGoogle ScholarPubMed
52.Kinon, BJ, Zhang, L, Millen, BA, etal. A multicenter, inpatient, phase 2, double-blind, placebo-controlled dose-ranging study of LY2140023 monohydrate in patients with DSM-IV schizophrenia. J Clin Psychopharmacol. 2011; 31(3): 349–355.CrossRefGoogle ScholarPubMed
53.Eli, Lilly. Lilly Announces Pomaglumetad Methionil Did Not Meet Primary Endpoint of Clinical Study (press release). July 11, 2012. http://newsroom.lilly.com/releasedetail.cfm?ReleaseID=690836 (accessed 19 July 2012).Google Scholar
54.Eli, Lilly. Lilly Stops Phase III Development of Pomaglumetad Methionil for the Treatment of Schizophrenia Based on Efficacy Results (press release). August 29, 2012. http://newsroom.lilly.com/releasedetail.cfm?ReleaseID=703018 (accessed 29 August 2012).Google Scholar