Risperidone Oral and Long-Acting Injectable; Paliperidone Oral and Long-Acting Injectable

Jonathan M. Meyer; Stephen M. Stahl

doi:10.1017/9781009002103.017

14 - Risperidone Oral and Long-Acting Injectable; Paliperidone Oral and Long-Acting Injectable

Published online by Cambridge University Press: 19 October 2021

Jonathan M. Meyer and

Stephen M. Stahl

Show author details

Jonathan M. Meyer: Affiliation:
University of California, San Diego
Stephen M. Stahl: Affiliation:
University of California, Riverside and San Diego

Book contents

Get access

Summary

Zotepine was approved in Japan in 1982, and is the first antipsychotic modeled on clozapine with relatively high serotonin 5HT2A affinity, lower dopamine D2 affinity, and a corresponding Positron Emission Tomography (PET) imaging profile that demonstrates wide separation between the 5HT2A and D2 occupancy curves in a manner unlike first-generation antipsychotics (FGAs) such as loxapine (see Chapter 11) [12–14]. Zotepine was never approved in the United States (US), Canada, the United Kingdom, Australia, or most European countries, leaving risperidone (US approval December 29, 1993) as the first commercially successful second-generation antipsychotic [15].

Information

Type: Chapter
Information: The Clinical Use of Antipsychotic Plasma Levels
Stahl's Handbooks
, pp. 267 - 295

DOI: https://doi.org/10.1017/9781009002103.017 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2021

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.)

Subscription

Individual access

Subscriptions are only available for individuals and not institutional access. Subscribe now

References

de Leon, J., Wynn, G., and Sandson, N. B. (2010). The pharmacokinetics of paliperidone versus risperidone. Psychosomatics, 51, 80–88.Google Scholar

Remington, G., Mamo, D., Labelle, A., et al. (2006). A PET study evaluating dopamine D2 receptor occupancy for long-acting injectable risperidone. Am J Psychiatry, 163, 396–401.Google Scholar

Uchida, H., Takeuchi, H., Graff-Guerrero, A., et al. (2011). Predicting dopamine D2 receptor occupancy from plasma levels of antipsychotic drugs: a systematic review and pooled analysis. J Clin Psychopharmacol, 31, 318–325.Google Scholar

Leucht, S., Samara, M., Heres, S., et al. (2014). Dose equivalents for second-generation antipsychotics: the minimum effective dose method. Schizophr Bull, 40, 314–326.Google Scholar

Schoretsanitis, G., Spina, E., Hiemke, C., et al. (2017). A systematic review and combined analysis of therapeutic drug monitoring studies for long-acting risperidone. Expert Rev Clin Pharmacol, 10, 965–981.Google Scholar

Schoretsanitis, G., Kane, J. M., Correll, C. U., et al. (2020). Blood levels to optimize antipsychotic treatment in clinical practice; a joint consensus statement of the American Society of Clinical Psychopharmacology (ASCP) and the Therapeutic Drug Monitoring (TDM) Task Force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP). J Clin Psychiatry, 81, https://doi.org/10.4088/JCP.4019cs13169.Google Scholar

Ezewuzie, N. and Taylor, D. (2006). Establishing a dose-response relationship for oral risperidone in relapsed schizophrenia. J Psychopharmacol, 20, 86–90.Google Scholar

Ikai, S., Remington, G., Suzuki, T., et al. (2012). A cross-sectional study of plasma risperidone levels with risperidone long-acting injectable: implications for dopamine D2 receptor occupancy during maintenance treatment in schizophrenia. J Clin Psychiatry, 73, 1147–1152.Google Scholar

Meyer, J. M. (2014). A rational approach to employing high plasma levels of antipsychotics for violence associated with schizophrenia: case vignettes. CNS Spectr, 19, 432–438.Google Scholar

Schoretsanitis, G., Spina, E., Hiemke, C., et al. (2018). A systematic review and combined analysis of therapeutic drug monitoring studies for oral paliperidone. Expert Rev Clin Pharmacol, 11, 625–639.Google Scholar

Arakawa, R., Ito, H., Takano, A., et al. (2008). Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia. Psychopharmacology, 197, 229–235.Google Scholar

Kapur, S., Zipursky, R., Remington, G., et al. (1997). PET evidence that loxapine is an equipotent blocker of 5-HT2 and D2 receptors: implications for the therapeutics of schizophrenia. Am J Psychiatry, 154, 1525–1529.Google Scholar

Barnas, C., Quiner, S., Tauscher, J., et al. (2001). In vivo (123)I IBZM SPECT imaging of striatal dopamine 2 receptor occupancy in schizophrenic patients. Psychopharmacology (Berl), 157, 236–242.Google Scholar

Tauscher, J., Kufferle, B., Asenbaum, S., et al. (2002). Striatal dopamine-2 receptor occupancy as measured with [123I]iodobenzamide and SPECT predicted the occurrence of EPS in patients treated with atypical antipsychotics and haloperidol. Psychopharmacology, 162, 42–49.Google Scholar

Nyberg, S., Farde, L., Eriksson, L., et al. (1993). 5-HT2 and D2 dopamine receptor occupancy in the living human brain: a PET study with risperidone. Psychopharmacology, 110, 265–272.Google Scholar

Ereshefsky, L. and Mascarenas, C. A. (2003). Comparison of the effects of different routes of antipsychotic administration on pharmacokinetics and pharmacodynamics. J Clin Psychiatry, 64, 18–23.Google Scholar

Samtani, M. N., Vermeulen, A., and Stuyckens, K. (2009). Population pharmacokinetics of intramuscular paliperidone palmitate in patients with schizophrenia: a novel once-monthly, long-acting formulation of an atypical antipsychotic. Clin Pharmacokinet, 48, 585–600.Google Scholar

Gomeni, R., Heidbreder, C., Fudala, P. J., et al. (2013). A model-based approach to characterize the population pharmacokinetics and the relationship between the pharmacokinetic and safety profiles of RBP-7000, a new, long-acting, sustained-released formulation of risperidone. J Clin Pharmacol, 53, 1010–1019.Google Scholar

Kapur, S., Zipursky, R. B., and Remington, G. (1999). Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia. Am J Psychiatry, 156, 286–293.Google Scholar

Huhn, M., Nikolakopoulou, A., Schneider-Thoma, J., et al. (2019). Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet, 394, 939–951.Google Scholar

Gaebel, W., Riesbeck, M., von Wilmsdorff, M., et al. (2010). Drug attitude as predictor for effectiveness in first-episode schizophrenia: results of an open randomized trial (EUFEST). Eur Neuropsychopharmacol, 20, 310–316.Google Scholar

Boulton, D. W., DeVane, C. L., Liston, H. L., et al. (2002). In vitro P-glycoprotein affinity for atypical and conventional antipsychotics. Life Sciences, 71, 163–169.Google Scholar

Nakagami, T., Yasui-Furukori, N., Saito, M., et al. (2005). Effect of verapamil on pharmacokinetics and pharmacodynamics of risperidone: in vivo evidence of involvement of P-glycoprotein in risperidone disposition. Clin Pharmacol Ther, 78, 43–51.Google Scholar

Wang, R., Sun, X., Deng, Y. S., et al. (2018). ABCB1 1199G > A polymorphism impacts transport ability of P-gp-mediated antipsychotics. DNA Cell Biol, 37, 325–329.+A+polymorphism+impacts+transport+ability+of+P-gp-mediated+antipsychotics.+DNA+Cell+Biol,+37,+325–329.>Google Scholar

Linnet, K. and Ejsing, T. B. (2008). A review on the impact of P-glycoprotein on the penetration of drugs into the brain: focus on psychotropic drugs. Eur Neuropsychopharmacol, 18, 157–169.Google Scholar

Hartter, S., Huwel, S., Lohmann, T., et al. (2003). How does the benzamide antipsychotic amisulpride get into the brain? – An in vitro approach comparing amisulpride with clozapine. Neuropsychopharmacology, 28, 1916–1922.Google Scholar

Janssen Pharmaceuticals Inc. (2019). Invega package insert. Titusville, NJ.Google Scholar

Janssen Pharmaceuticals Inc. (2020). Risperdal package insert. Titusville, NJ.Google Scholar

O’Brien, F. E., Dinan, T. G., Griffin, B. T., et al. (2012). Interactions between antidepressants and P-glycoprotein at the blood-brain barrier: clinical significance of in vitro and in vivo findings. Br J Pharmacol, 165, 289–312.Google Scholar

Zanger, U. M. and Schwab, M. (2013). Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther, 138, 103–141.Google Scholar

de Leon, J., Sandson, N. B., and Cozza, K. L. (2008). A preliminary attempt to personalize risperidone dosing using drug–drug interactions and genetics, Part II. Psychosomatics, 48, 347–361.Google Scholar

Verbeeck, R. K. (2008). Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction. Eur J Clin Pharmacol, 64, 1147–1161.Google Scholar

Meyer, J. M. (2018). Pharmacotherapy of psychosis and mania. In Brunton, L. L., Hilal-Dandan, R. and Knollmann, B. C., eds., Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 13th edn. Chicago, IL: McGraw-Hill, pp. 279–302.Google Scholar

Selmin, F., Blasi, P., and DeLuca, P. P. (2012). Accelerated polymer biodegradation of risperidone poly(D, L-lactide-co-glycolide) microspheres. AAPS PharmSciTech, 13, 1465–1472.Google Scholar

Fleischhacker, W. W., Eerdekens, M., Karcher, K., et al. (2003). Treatment of schizophrenia with long-acting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic. J Clin Psychiatry, 64, 1250–1257.Google Scholar

Wilson, W. H. (2004). A visual guide to expected blood levels of long-acting injectable risperidone in clinical practice. J Psychiatr Pract, 10, 393–401.Google Scholar

Kane, J. M., Eerdekens, M., Lindenmayer, J. P., et al. (2003). Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am J Psychiatry, 160, 1125–1132.Google Scholar

Meltzer, H. Y., Lindenmayer, J. P., Kwentus, J., et al. (2014). A six month randomized controlled trial of long acting injectable risperidone 50 and 100mg in treatment resistant schizophrenia. Schizophr Res, 154, 14–22, https://doi.org/10.1016/j.schres.2014.1002.1015.Google Scholar

Schoretsanitis, G., Spina, E., Hiemke, C., et al. (2018). A systematic review and combined analysis of therapeutic drug monitoring studies for long-acting paliperidone. Expert Rev Clin Pharmacol, 11, 1237–1253.Google Scholar

Janssen Pharmaceuticals Inc. (2020). Risperdal Consta package insert. Titusville, NJ.Google Scholar

Gefvert, O., Eriksson, B., Persson, P., et al. (2005). Pharmacokinetics and D2 receptor occupancy of long-acting injectable risperidone (Risperdal Consta) in patients with schizophrenia. Int J Neuropsychopharmacol, 8, 27–36.Google Scholar

Janssen Pharmaceuticals Inc. (2019). Invega Trinza package insert. Titusville, NJ.Google Scholar

Haddad, P., Lambert, T., and Lauriello, J., eds. (2016). Antipsychotic Long-Acting Injections, 2nd edn. New York: Oxford University Press.Google Scholar

Nasser, A. F., Henderson, D. C., Fava, M., et al. (2016). Efficacy, safety, and tolerability of RBP-7000 once-monthly risperidone for the treatment of acute schizophrenia: an 8-week, randomized, double-blind, placebo-controlled, multicenter phase 3 study. J Clin Psychopharmacol, 36, 130–140.Google Scholar

Ivaturi, V., Gopalakrishnan, M., Gobburu, J. V. S., et al. (2017). Exposure-response analysis after subcutaneous administration of RBP-7000, a once-a-month long-acting Atrigel formulation of risperidone. Br J Clin Pharmacol, 83, 1476–1498.Google Scholar

Southard, G. L., Dunn, R. L., and Garrett, S. (1998). The drug delivery and biomaterial attributes of the ATRIGEL technology in the treatment of periodontal disease. Expert Opin Investig Drugs, 7, 1483–1491.Google Scholar

Meyer, J. M. (2018). Risperidone extended-release injectable suspension. Curr Psychiatr, 17, 23–33.Google Scholar

Laffont, C. M., Gomeni, R., Zheng, B., et al. (2014). Population pharmacokinetics and prediction of dopamine D2 receptor occupancy after multiple doses of RBP-7000, a new sustained-release formulation of risperidone, in schizophrenia patients on stable oral risperidone treatment. Clin Pharmacokinet, 53, 533–543.Google Scholar

Laffont, C. M., Gomeni, R., Zheng, B., et al. (2015). Population pharmacokinetic modeling and simulation to guide dose selection for RBP-7000, a new sustained-release formulation of risperidone. J Clin Pharmacol, 55, 93–103.Google Scholar

Indivior Inc. (2019). Perseris package insert. North Chesterfield, VA 23235.Google Scholar

Janssen Pharmaceuticals Inc. (2019). Invega Sustenna package insert. Titusville, NJ.Google Scholar

Pandina, G. J., Lindenmayer, J. P., Lull, J., et al. (2010). A randomized, placebo-controlled study to assess the efficacy and safety of 3 doses of paliperidone palmitate in adults with acutely exacerbated schizophrenia. J Clin Psychopharmacol, 30, 235–244, https://doi.org/210.1097/JCP.1090b1013e3181dd3103.Google Scholar

Chouinard, G., Jones, B., Remington, G., et al. (1993). A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psychopharmacol, 13, 25–40.Google Scholar

Marder, S. R. and Meibach, R. C. (1994). Risperidone in the treatment of schizophrenia. Am J Psychiatry, 151, 825–835.Google Scholar

Peuskens, J. (1995). Risperidone in the treatment of patients with chronic schizophrenia: a multi-national, multi-centre, double-blind, parallel-group study versus haloperidol. Risperidone Study Group. Br J Psychiatry, 166, 712–726; discussion 727–733.Google Scholar

Merlo, M. C., Hofer, H., Gekle, W., et al. (2002). Risperidone, 2 mg/day vs. 4 mg/day, in first-episode, acutely psychotic patients: treatment efficacy and effects on fine motor functioning. J Clin Psychiatry, 63, 885–891.Google Scholar

Li, C., Xia, J., and Wang, J. (2009). Risperidone dose for schizophrenia. Cochrane Database Syst Rev, CD007474.Google Scholar

Kapur, S., Zipursky, R., Jones, C., et al. (2000). Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry, 157, 514–520.Google Scholar

Remington, G., Kapur, S., and Zipursky, R. (1998). The relationship between risperidone plasma levels and dopamine D2 occupancy: a positron emission tomographic study. J Clin Psychopharmacol, 18, 82–83.Google Scholar

Karlsson, P., Hargarter, L., Dencker, E., et al. (2007). Pharmacokinetics and dopamine D2 and serotonin 5-HT2a receptor occupancy of paliperidone in healthy subjects: two open-label, single-dose studies (PAL-115). Pharmacopsychiatry, 40, A106.Google Scholar

Leucht, S., Crippa, A., Siafis, S., et al. (2020). Dose-response meta-analysis of antipsychotic drugs for acute schizophrenia. Am J Psychiatry, 177, 342–353.Google Scholar

Samtani, M. N., Gopal, S., Gassmann-Mayer, C., et al. (2011). Dosing and switching strategies for paliperidone palmitate: based on population pharmacokinetic modelling and clinical trial data. CNS Drugs, 25, 829–845.Google Scholar

Accessibility standard: Unknown

Why this information is here

This section outlines the accessibility features of this content - including support for screen readers, full keyboard navigation and high-contrast display options. This may not be relevant for you.

Accessibility Information

Accessibility compliance for the HTML of this chapter is currently unknown and may be updated in the future.