Hostname: page-component-848d4c4894-wzw2p Total loading time: 0 Render date: 2024-06-12T08:23:53.965Z Has data issue: false hasContentIssue false
  • English
  • Français

How to classify antipsychotics: time to ditch dichotomies?

Published online by Cambridge University Press:  14 November 2023

Robert A. McCutcheon Open the ORCID record for Robert A. McCutcheon [Opens in a new window] ,
Alistair Cannon Open the ORCID record for Alistair Cannon [Opens in a new window] ,
Sita Parmer  and
Oliver D. Howes Open the ORCID record for Oliver D. Howes [Opens in a new window]
Robert A. McCutcheon*
Affiliation:
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK; Oxford Health NHS Foundation Trust, Oxford, UK; and Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
Alistair Cannon
Affiliation:
South London and Maudsley NHS Foundation Trust, London, UK
Sita Parmer
Affiliation:
South London and Maudsley NHS Foundation Trust, London, UK
Oliver D. Howes
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; South London and Maudsley NHS Foundation Trust, London, UK; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK; and H. Lundbeck A/S, Copenhagen, Denmark
*
Correspondence: Robert A. McCutcheon. Email: robert.mccutcheon@psych.ox.ac.uk
Get access Rights & Permissions [Opens in a new window]

Summary

The dichotomies of ‘typical/atypical’ or ‘first/second generation’ have been employed for several decades to classify antipsychotics, but justification for their use is not clear. In the current analysis we argue that this classification is flawed from both clinical and pharmacological perspectives. We then consider what approach should ideally be employed in both clinical and research settings.

Keywords

Schizophreniapharmacologynomenclaturepsychosismedication
Type
Discussion
Information
The British Journal of Psychiatry , Volume 224 , Issue 1 , January 2024 , pp. 20 - 25
Check for updates
Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press on behalf of the Royal College of Psychiatrists

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

Zohar, J, Nutt, DJ, Kupfer, DJ, Moller, H-J, Yamawaki, S, Spedding, M, et al. A proposal for an updated neuropsychopharmacological nomenclature. Eur Neuropsychopharmacol 2014; 24: 1005–14.CrossRefGoogle ScholarPubMed
Taylor, D. The Maudsley Prescribing Guidelines in Psychiatry (14th edn). Wiley-Blackwell, 2021.CrossRefGoogle Scholar
Seeman, P. Antipsychotic drugs, dopamine receptors, and schizophrenia. Clin Neurosci Res 2001; 1: 53–60.Google Scholar
Huhn, M, Nikolakopoulou, A, Schneider-Thoma, J, Krause, M, Samara, M, Peter, N, et al. 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 2019; 394: 939–51.Google Scholar
McCutcheon, RA, Harrison, PJ, Howes, OD, McGuire, PK, Taylor, D, Pillinger, T. Data driven taxonomy for antipsychotic medication: a New classification system. Biol Psychiatry 2023; 94: 561–8.Google Scholar
Costall, B, Naylor, RJ. Detection of the neuroleptic properties of clozapine, sulpiride and thioridazine. Psychopharmacologia 1975; 43: 69–74.Google Scholar
Kinon, BJ, Lieberman, JA. Mechanisms of action of atypical antipsychotic drugs: a critical analysis. Psychopharmacology (Berl) 1996; 124: 2–34.CrossRefGoogle ScholarPubMed
Mizuno, Y, McCutcheon, RA, Brugger, SP, Howes, OD. Heterogeneity and efficacy of antipsychotic treatment for schizophrenia with or without treatment resistance: a meta-analysis. Neuropsychopharmacology 2020; 45: 622–31.CrossRefGoogle ScholarPubMed
Kaar, SJ, Natesan, S, McCutcheon, R, Howes, OD. Antipsychotics: mechanisms underlying clinical response and side-effects and novel treatment approaches based on pathophysiology. Neuropharmacology 2020; 172: 107704.CrossRefGoogle ScholarPubMed
Kapur, S, Zipursky, R, Jones, C, Remington, G, Houle, S. Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry 2000; 157: 514–20.CrossRefGoogle ScholarPubMed
Farde, L, Nordström, AL, Wiesel, FA, Pauli, S, Halldin, C, Sedvall, G. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. Arch Gen Psychiatry 1992; 49: 538–44.CrossRefGoogle ScholarPubMed
Seeman, P. Atypical antipsychotics: mechanism of action. Can J Psychiatry 2002; 47: 27–38.Google Scholar
Leucht, S, Leucht, C, Huhn, M, Chaimani, A, Mavridis, D, Helfer, B, et al. Sixty years of placebo-controlled antipsychotic drug trials in acute schizophrenia: systematic review, Bayesian meta-analysis, and meta-regression of efficacy predictors. Am J Psychiatry 2017; 174: 927–42.Google Scholar
Beasley, CM Jr, Tollefson, G, Tran, P, Satterlee, W, Sanger, T, Hamilton, S. Olanzapine versus placebo and haloperidol: acute phase results of the north American double-blind olanzapine trial. Neuropsychopharmacology 1996; 14: 111–23.CrossRefGoogle ScholarPubMed
Kapur, S, Zipursky, RB, Remington, G, Jones, C, DaSilva, J, Wilson, AA, et al. 5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation. Am J Psychiatry 1998; 155: 921–8.Google Scholar
Kapur, S, Zipursky, R, Roy, P, Jones, C, Remington, G, Reed, K, et al. The relationship between D2 receptor occupancy and plasma levels on low dose oral haloperidol: a PET study. Psychopharmacology 1997; 131: 148–52.CrossRefGoogle ScholarPubMed
Leucht, S, Wahlbeck, K, Hamann, J, Kissling, W. New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet 2003; 361: 1581–9.Google Scholar
Rochon, PA, Stukel, TA, Sykora, K, Gill, S, Garfinkel, S, Anderson, GM, et al. Atypical antipsychotics and parkinsonism. Arch Intern Med 2005; 165: 1882–8.Google Scholar
Lobo, MC, Whitehurst, TS, Kaar, SJ, Howes, OD. New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics. Neurosci Biobehav Rev 2022; 132: 324–61.Google Scholar
Kapur, S, Langlois, X, Vinken, P, Megens, AAHP, De Coster, R, Andrews, JS. The differential effects of atypical antipsychotics on prolactin elevation are explained by their differential blood-brain disposition: a pharmacological analysis in rats. J Pharmacol Exp Ther 2002; 302: 1129–34.Google Scholar
Loryan, I, Melander, E, Svensson, M, Payan, M, König, F, Jansson, B, et al. In-depth neuropharmacokinetic analysis of antipsychotics based on a novel approach to estimate unbound target-site concentration in CNS regions: link to spatial receptor occupancy. Mol Psychiatry 2016; 21: 1527–36.Google Scholar
Carbon, M, Kane, JM, Leucht, S, Correll, CU. Tardive dyskinesia risk with first- and second-generation antipsychotics in comparative randomized controlled trials: a meta-analysis. World Psychiatry 2018; 17: 330–40.CrossRefGoogle ScholarPubMed
Tenback, DE, van Harten, PN. Epidemiology and risk factors for (tardive) dyskinesia. Int Rev Neurobiol 2011; 98: 211–30.CrossRefGoogle ScholarPubMed
Leucht, S, Corves, C, Arbter, D, Engel, RR, Li, C, Davis, JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 2009; 373: 31–41.Google Scholar
Tollefson, GD, Beasley, CM Jr, Tran, PV, Street, JS, Krueger, JA, Tamura, RN, et al. Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. Am J Psychiatry 1997; 154: 457–65.Google Scholar
Lieberman, JA, Stroup, TS, McEvoy, JP, Swartz, MS, Rosenheck, RA, Perkins, DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353: 1209–23.Google Scholar
Jones, PB, Barnes, TRE, Davies, L, Dunn, G, Lloyd, H, Hayhurst, KP, et al. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: cost utility of the latest antipsychotic drugs in schizophrenia study (CUtLASS 1). Arch Gen Psychiatry 2006; 63: 1079–87.Google Scholar
Kahn, RS, Fleischhacker, WW, Boter, H, Davidson, M, Vergouwe, Y, Keet, IPM, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 2008; 371: 1085–97.Google Scholar
McCutcheon, RA, Keefe, RSE, McGuire, PK. Cognitive impairment in schizophrenia: aetiology, pathophysiology, and treatment. Mol Psychiatry 2023: 1–17.Google Scholar
Keefe, RSE. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE trial. Arch Gen Psychiatry 2007; 64: 633.Google Scholar
Baldez, DP, Biazus, TB, Rabelo-da-Ponte, FD, Nogaro, GP, Martins, DS, Kunz, M, et al. The effect of antipsychotics on the cognitive performance of individuals with psychotic disorders: network meta-analyses of randomized controlled trials. Neurosci Biobehav Rev 2021; 126: 265–75.Google Scholar
Duncan, GE, Zorn, S, Lieberman, JA. Mechanisms of typical and atypical antipsychotic drug action in relation to dopamine and NMDA receptor hypofunction hypotheses of schizophrenia. Mol Psychiatry 1999; 4: 418–28.CrossRefGoogle ScholarPubMed
Meltzer, HY. What's atypical about atypical antipsychotic drugs? Curr Opin Pharmacol 2004; 4: 53–7.CrossRefGoogle ScholarPubMed
Kroeze, WK, Hufeisen, SJ, Popadak, BA, Renock, SM, Steinberg, S, Ernsberger, P, et al. H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology 2003; 28: 519–26.Google Scholar
Kapur, S, Seeman, P. Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action. J Psychiatry Neurosci 2000; 25: 161–6.Google ScholarPubMed
Zhu, Y, Zhang, C, Siafis, S, Zhuo, K, Zhu, D, Wu, H, et al. Prolactin levels influenced by antipsychotic drugs in schizophrenia: a systematic review and network meta-analysis. Schizophr Res 2021; 237: 20–5.Google Scholar
Sparshatt, A, Taylor, D, Patel, MX, Kapur, S. A systematic review of aripiprazole – dose, plasma concentration, receptor occupancy, and response: implications for therapeutic drug monitoring. J Clin Psychiatry 2010; 71: 1447–56.CrossRefGoogle ScholarPubMed
Brannan, SK, Sawchak, S, Miller, AC, Lieberman, JA, Paul, SM, Breier, A. Muscarinic cholinergic receptor agonist and peripheral antagonist for schizophrenia. N Engl J Med 2021; 384: 717–26.CrossRefGoogle ScholarPubMed
Koblan, KS, Kent, J, Hopkins, SC, Krystal, JH, Cheng, H, Goldman, R, et al. A Non-D2-receptor-binding drug for the treatment of schizophrenia. N Engl J Med 2020; 382: 1497–506.Google Scholar
Pillinger, T, Howes, OD, Correll, CU, Leucht, S, Huhn, M, Schneider-Thoma, J, et al. Antidepressant and antipsychotic side-effects and personalised prescribing: a systematic review and digital tool development. The Lancet Psychiatry 2023; 10: 860–76.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.