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12 - Important Concepts about Second-Generation Antipsychotics

Published online by Cambridge University Press:  19 October 2021

Jonathan M. Meyer
University of California, San Diego
Stephen M. Stahl
University of California, Riverside and San Diego
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While FGAs share the common mechanism of action (MOA) of D2 antagonism, SGAs are a heterogeneous group that includes agents with limited D2 occupancy and the dopamine partial agonists [3]. Among SGAs whose principal MOA is D2 blockade, positron imaging tomography (PET) studies indicate that the ‘sweet spot’ for receptor occupancy is the same as for FGAs, 65%–80%, with decreased response rates below this threshold, and greater risk for neurological adverse effects above 80% [18].

The Clinical Use of Antipsychotic Plasma Levels
Stahl's Handbooks
, pp. 241 - 248
Publisher: Cambridge University Press
Print publication year: 2021

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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, 939951.
Pillinger, T., McCutcheon, R. A., Vano, L., et al. (2020). Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry, 7, 6477.
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. 279302.
Poyurovsky, M. and Weizman, A. (2018). Very low-dose mirtazapine (7.5 mg) in treatment of acute antipsychotic-associated akathisia. J Clin Psychopharmacol, 38, 609611.
Kahn, R. S., Winter van Rossum, I., Leucht, S., et al. (2018). Amisulpride and olanzapine followed by open-label treatment with clozapine in first-episode schizophrenia and schizophreniform disorder (OPTiMiSE): a three-phase switching study. Lancet Psychiatry, 5, 797807.
Meyer, J. M. and Stahl, S. M. (2019). The Clozapine Handbook. Cambridge: Cambridge University Press.
Xiong, G. L., Pinkhasov, A., Mangal, J. P., et al. (2020). QTc monitoring in adults with medical and psychiatric comorbidities: expert consensus from the Association of Medicine and Psychiatry. J Psychosom Res, 135, 110138.
Indik, J. H., Pearson, E. C., Fried, K., et al. (2006). Bazett and Fridericia QT correction formulas interfere with measurement of drug-induced changes in QT interval. Heart Rhythm, 3, 10031007.
Nielsen, J., Graff, C., Kanters, J. K., et al. (2011). Assessing QT prolongation of antipsychotic drugs. CNS Drugs, 25, 473490.
Vandenberk, B., Vandael, E., Robyns, T., et al. (2016). Which QT correction formulae to use for QT monitoring? J Am Heart Assoc, 5, e003264.
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,
Leucht, S., Samara, M., Heres, S., et al. (2016). Dose equivalents for antipsychotic drugs: the DDD method. Schizophr Bull, 42 Suppl 1, S9094.
Leucht, S., Crippa, A., Siafis, S., et al. (2020). Dose-response meta-analysis of antipsychotic drugs for acute schizophrenia. Am J Psychiatry, 177, 342353.
Asmal, L., Flegar, S. J., Wang, J., et al. (2013). Quetiapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev, CD006625.
Vanasse, A., Blais, L., Courteau, J., et al. (2016). Comparative effectiveness and safety of antipsychotic drugs in schizophrenia treatment: a real-world observational study. Acta Psychiatr Scand, 134, 374384.
Meyer, J. M., Davis, V. G., Goff, D. C., et al. (2008). Change in metabolic syndrome parameters with antipsychotic treatment in the CATIE Schizophrenia Trial: prospective data from phase 1. Schizophr Res, 101, 273286.
Meyer, J. M. (2010). Antipsychotics and metabolics in the post-CATIE era. Curr Top Behav Neurosci, 4, 2342.
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, 514520.
Kelly, D. L., Richardson, C. M., Yang, Y., et al. (2006). Plasma concentrations of high-dose olanzapine in a double-blind crossover study. Hum Psychopharmacol, 21, 393398.
Schwieler, L., Linderholm, K. R., Nilsson-Todd, L. K., et al. (2008). Clozapine interacts with the glycine site of the NMDA receptor: electrophysiological studies of dopamine neurons in the rat ventral tegmental area. Life Sci, 83, 170175.
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, 318325.
McKinzie, D. L. and Bymaster, F. P. (2012). Muscarinic mechanisms in psychotic disorders. Handb Exp Pharmacol, 213, 233265.
Pei, Y., Asif-Malik, A., and Canales, J. J. (2016). Trace amines and the trace amine-associated receptor 1: pharmacology, neurochemistry, and clinical implications. Front Neurosci, 10, 148.
Dedic, N., Jones, P. G., Hopkins, S. C., et al. (2019). SEP-363856, a novel psychotropic agent with a unique, non-D2 receptor mechanism of action. J Pharmacol Exp Ther, 371, 114.
Meyer, J. M. (2020). Monitoring and improving antipsychotic adherence in outpatient forensic diversion programs. CNS Spectr, 25, 136144.
Devinsky, O., Honigfeld, G., and Patin, J. (1991). Clozapine-related seizures. Neurology, 41, 369371.
Pacia, S. V. and Devinsky, O. (1994). Clozapine-related seizures: experience with 5,629 patients. Neurology, 44, 22472249.
Vyas, P., Hwang, B. J., and Brasic, J. R. (2019). An evaluation of lumateperone tosylate for the treatment of schizophrenia. Expert Opin Pharmacother, 30, 17.
Meyer, J. M. (2020). Lumateperone for schizophrenia. Curr Psychiatr, 19, 3339.
Mamo, D., Graff, A., Mizrahi, R., et al. (2007). Differential effects of aripiprazole on D(2), 5-HT(2), and 5-HT(1A) receptor occupancy in patients with schizophrenia: a triple tracer PET study. Am J Psychiatry, 164, 14111417.
Sparshatt, A., Taylor, D., Patel, M. X., et al. (2010). A systematic review of aripiprazole – dose, plasma concentration, receptor occupancy, and response: implications for therapeutic drug monitoring. J Clin Psychiatry, 71, 14471556.
Girgis, R. R., Slifstein, M., D’Souza, D., et al. (2016). Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [(11)C]-(+)-PHNO. Psychopharmacology (Berl), 233, 35033512.

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