Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-25T16:53:36.911Z Has data issue: false hasContentIssue false
  • English
  • Français

Eficacia de los antipsicóticos: relación con la ocupación óptima de los receptores D2

Published online by Cambridge University Press:  12 May 2020

Luca Pani ,
Luigi Pira  and
Giorgio Marchese
Luca Pani
Affiliation:
PharmaNess S.c.a.r.l., Parque Tecnológico-Investigación Sardegna, Pula (CA), Italia CNR, Instituto de Tecnología Biomédica. Cagliari, Parque Tecnológico - Investigación Sardegna, Pula (CA), Italia
Luigi Pira
Affiliation:
PharmaNess S.c.a.r.l., Parque Tecnológico-Investigación Sardegna, Pula (CA), Italia
Giorgio Marchese
Affiliation:
PharmaNess S.c.a.r.l., Parque Tecnológico-Investigación Sardegna, Pula (CA), Italia
Get access

Resumen

Hay diferencias clínicamente importantes en la seguridad y tolerabilidad de los antipsicóticos dependiendo de los distintos tipos y de sus formulaciones. Las características de la interacción bioquímica entre el antipsicótico y el receptor D2 pueden ser la base de estas diferencias. Este artículo revisa la información actual sobre la relación entre la ocupación del antipsicótico por el receptor y la respuesta clínica. Se hizo una búsqueda en la literatura introduciendo las palabras clave “antipsicótico o neuroléptico”, “receptor”, “ocupación”, “dopamina” y “D2” y se complementó con búsquedas manuales en la literatura. Los datos de las pruebas de neuroimagen y clínicas, generalmente, confirmaron que la ocupación óptima de los receptores D2 del núcleo estriado se sitúa en “una ventana térapeutica” entre ∼ 65% y ∼ 80%; sin embargo, las propiedades farmacocinéticas y farmacodinámicas del fármaco también deberían tenerse en cuenta para evaluar totalmente sus efectos terapéuticos. Deberían realizarse nuevas investigaciones, quizá, en modelos preclínicos, para deetrminar la ocupación de los receptores D2 en varias regiones cerebrales y la duración óptima del bloqueo de los receptores D2 para maximizar los perfiles de eficacia y tolerabilidad de los antipsicóticos atípicos y mejorar los resultados del tratamiento de los pacientes con esquizofrenia.

Keywords

AntipsicóticoAtípicoDopaminaReceptorOcupaciónSíntomas extrapiramidales
Type
Revisión
Information
European Psychiatry (Ed. Española) , Volume 14 , Issue 7 , October 2007 , pp. 325 - 334
Copyright
Copyright © European Psychiatric Association 2007

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

Bibliografía

ADA. Consensus development conference on antipsychotic drugs and obesity and diabetes. J Clin Psychiatry 2004;65(2):267–72.CrossRefGoogle Scholar
Adams, CE, Fenton, MK, Quraishi, S, David, AS. Systematic metareview of depot antipsychotic drus for people with schizophrenia. Br J Psychiatry 2001;179:290–9.CrossRefGoogle Scholar
Bai, YM, Chen, TT, Wu, B, Hung, CH, Lin, WK, Hu, TM, et al. A comparative efficacy and safety study of long-acting risperidone injection and risperidone oral tablets among hospitalized patients: 12-week randomized, single-blind study. Pharmacopsychiatry 2006;39(4): 135–41.Google ScholarPubMed
Balijepalli, S, Boyd, MR, Ravindranath, V. Inhibition of mitochondrial complex I by haloperidol: the role of thiol oxidation. Neuropharmacology 1999;38(4):567–77.CrossRefGoogle ScholarPubMed
Bressan, RA, Erlandsson, K, Spencer, EP, Eli, PJ, Pilowsky, LS. Prolactinemia is uncoupled from central D2/D3 dopamine receptor occupancy in amisulpride treated patients. Psychopharmacology (Berl) 2004;175(3):367–73.CrossRefGoogle ScholarPubMed
Broich, K, Grunwald, F, Kasper, S, Klemm, E, Biersack, HJ, Moller, HJ. D2-dopamine receptor occupancy measured by IBZM-SPECT in relation to extrapyramidal side effects. Pharmacopsychiatry 1998;31(5):159–62.CrossRefGoogle ScholarPubMed
Brook, S, Walden, J, Benattia, I, Siu, CO, Romano, SJ. Ziprasidone and haloperidol in the treatment of acute exacerbation of schizophrenia and schizoaffective disorder: comparison of intramuscular and oral formulations in a 6-week, randomized, blinded-assessment study. Psychopharmacology (Berl) 2005;178(4):514–23.CrossRefGoogle Scholar
Casey, DE. Pathophysiology of antipsychotic drug-induced movement disorders. J Clin Psychiatry 2004;65(Suppl. 9):25–8.Google ScholarPubMed
Compton, MT, Miller, AH. Antipsychotic-induced hyperprolactinemia and sexual dysfunction. Psychopharmacol Bull 2002;36(1):143–64.Google ScholarPubMed
Conley, R, Gupta, S, Sathyan, G. Clinical spectrum of the osmoticcontrolled ralease oral delivery system (OROS), an advanced oral delivery form. Curr Med Res Opin 2006;22(l):1879–92.CrossRefGoogle Scholar
Conley, RR, Kelly, DL. Second-generation antipsychotics for schizophrenia: a review of clinical pharmacology and medication-associated side effects. Isr J Psychiatry Relat Sci 2005;42(1):51–60.Google ScholarPubMed
Crocker, AD, Hemsley, KM. An animal model of extrapyramidal side effects induced by antipsychotic drugs: relationship with D2 dopamine receptor occupancy. Prog Neuropsychopharmacol Biol Psychiatry 2001;25(3):573–90.CrossRefGoogle ScholarPubMed
Davidson, M, Emsley, R, Kramer, M, Ford, L, Gassmann-Mayer, C, Lim, P, et al. Efficacy, safety and effect on functioning of paliperidone extended release tablets in the treatment of acute schizophrenia: an international 6-week placebo-controlled study. Schizophr Res 2006;81(Suppl 1):43.Google Scholar
Davis, JM, Matalon, L, Watanabe, MD, Blake, L, Metalon, L. Depot antipsychotic drugs. Place in therapy. Drugs 1994;47(5):741–73.CrossRefGoogle ScholarPubMed
de Haan, L, van Bruggen, M, Lavalaye, J, Booij, J, Dingemans, PM, Linszen, D. Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study. Am J Psychiatry 2003; 160(2):303–9.CrossRefGoogle ScholarPubMed
Edwards, NC, Rupnow, MF, Pashos, CL, Botteman, MF, Diamond, RJ. Cost-effectiveness model of long-acting risperidone in schizophrenia in the US. Pharmacoeconomics 2005;23(3):299–314.CrossRefGoogle ScholarPubMed
Eerdekens, M, Van Hove, I, Remmerie, B, Mannaert, E. Pharmacokinetics and tolerability of long-acting risperidone in schizophrenia. Schizophr Res 2004;70(1):91–100.CrossRefGoogle Scholar
Ereshefsky, L, Mannaert, E. Pharmacokinetic profile and clinical efficacy of long-acting risperidone: potential benefits of combining an atypical antipsychotic and a new delivery system. Drugs R D 2005;6(3):129–37.CrossRefGoogle Scholar
Ereshefsky, L, Mascarenas, CA. Comparison of the effects of different routes of antipsychotic administration on pharmacokinetics and pharmacodynamics. J Clin Psychiatry 2003;64(Suppl. 16): 18–23.Google ScholarPubMed
Ereshefsky, L, Saklad, SR, Tran-Johnson, T, Toney, G, Lyman, RC, Davis, CM. Kinetics and clinical evaluation of haloperidol decanoate loading dose regimen. Psychopharmacol Bull 1990;26(1): 108–14.Google ScholarPubMed
Farde, L. Brain imaging of schizophrenia—the dopamine hypothesis. Schizophr Res 1997;28(2-3): 157–62.CrossRefGoogle ScholarPubMed
Farde, L, Nordstrom, AL, Wiesel, FA, Pauli, S, Halldin, C, Sedvall, G. Positron emission tomographic analysis of central DI and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. Arch Gen Psychiatry 1992;49(7):538–44.CrossRefGoogle Scholar
Fleischhacker, WW, Eerdekens, M, Karcher, K, Remington, G, Llorca, PM, Chrzanowski, W, et al. Treatment of schizophrenia with longacting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic. J Clin Psychiatry 2003;64(10):1250–7.CrossRefGoogle Scholar
Frankle, W, Narendan, R, Gil, R, Hwang, D, Scher, E, Cangiano, C, et al. Occupancy of dopamine D2 receptors by aripiprazole at steady State dosing in schizophrenia measured with [18F]fallypride PET. American College of Neuropsychopharmacology annual meeting Abstract 2004;135.Google Scholar
Gastpar, M, Masiak, M, Latif, MA, Frazzingaro, S, Medori, R, Lombertie, ER. Sustained improvement of clinical outcome with risperidone long-acting injectable in psychotic patients previously treated with olanzapine. J Psychopharmacol 2005;19(5 Suppl):32–8.CrossRefGoogle ScholarPubMed
Gefvert, O, Eriksson, B, Persson, P, Helldin, L, Bjorner, A, Mannaert, E, et al. Pharmacokinetics and D2 receptor occupancy of longacting injectable risperidone (Risperdal Consta) in patients with schizophrenia. Int J Neuropsychopharmacol 2005;8(1): 27–36.CrossRefGoogle Scholar
Gharabawi, GM, Bossie, CA, Zhu, Y, Mao, L, Lasser, RA. An assessment of emergent tardive dyskinesia and existing dyskinesia in patients receiving long-acting, injectable risperidone: results from a long-term study. Schizophr Res 2005;77(2–3):129–39.CrossRefGoogle ScholarPubMed
Glick, I, Davis, J, Chen, N. A meta-analysis of the efficacy of secondgeneration antipsychotics. Schizophr Res 2003;60(1 Suppl):285.CrossRefGoogle Scholar
Grunder, G, Carlsson, A, Wong, DF. Mechanism of new antipsychotic medications: occupancy is not just antagonism. Arch Gen Psychiatry 2003;60(10):974–7.CrossRefGoogle Scholar
Hiemke, C, Dragicevic, A, Grunder, G, Hatter, S, Sachse, J, Vemaleken, I, et al. Therapeutic monitoring of new antipsychotic drugs. Ther Drug Monit 2004;26(2): 156–60.CrossRefGoogle ScholarPubMed
Hirsch, SR, Kissling, W, Bauml, J, Power, A, O'Counor, R. A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia. J Clin Psychiatry 2002;63(6):516–23.Google ScholarPubMed
Hogarty, GE, Schooler, NR, Ulrich, R, Mussare, F, Ferro, P, Herron, E. Fluphenazine and social therapy in the aftercare of schizophrenic patients. Relapse anaiyses of a two-year controlled study of fluphenazine decanoate and fluphenazine hydrochloride. Arch Gen Psychiatry 1979;36(12): 1283–94.CrossRefGoogle ScholarPubMed
Kane, J, Kramer, M, Ford, L, Gassmann-Mayer, C, Lim, P, Eerdekens, M. Patients with acute schizophrenia: treatment with three fixed dosages of oral paliperidone extended-release tablets in a 6-week placebo controlled study. Schizophr Res 2007;90:147–61.CrossRefGoogle Scholar
Kane, JM, Carson, WH, Saha, AR, McQuade, RD, Ingenito, GG, Zimbroff, DL, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2002;63(9):763–71.CrossRefGoogle ScholarPubMed
Kane, JM, Eerdekens, M, Lindenmayer, JP, Keith, SJ, Lesem, M, Karcher, K. Long-acting injectable risperidone: efficacy and safety of the first long acting atypical antipsychotic. Am J Psychiatry 2003;160(6):1125–32.CrossRefGoogle ScholarPubMed
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(2): 161–6.Google 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(4):514–20.CrossRefGoogle ScholarPubMed
Kapor, S, Zipursky, R, Jones, C, Shammi, CS, Remington, G, Seeman, P. A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy. Arch Gen Psychiatry 2000;57(6):553–9.CrossRefGoogle Scholar
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(7):921–8.Google ScholarPubMed
Karlsson, P, Dencker, E, Nyberg, S, Mannaert, E, Boom, S, Talluri, K, et al. Pharmacokinetics, dopamine D2 and serotonin 5-HT2A receptor occupancy and safety profile of paliperidone extended-ralease in healthy subjects. Schizophr Res 2006;81(l):85–6.Google Scholar
Kasper, S, Lerman, MN, McQuade, RD, Saha, A, Carson, WH, Ali, M, et al. Efficacy and safety of aripiprazole vs. haloperidol for longterm maintenance treatment following acute relapse of schizophrenia. Int J Neuropsychopharmacol 2003;6(4):325–37.CrossRefGoogle Scholar
Lasser, R, Bossie, C, Gharabawi, G, Baldessarini, R. Clinical improvement in 336 stable chronically psychotic patients changed from oral to long-acting risperidone: a 12-month open trial. Int J Neuropsychopharmacol 2005;8:1–12.CrossRefGoogle ScholarPubMed
Lasser, RA, Bossie, CA, Gharabawi, GM, Kane, JM. Remission in schizophrenia: results from a 1-year study of long-acting risperidone injection. Schizophr Res 2005;77(2–3):215–27.CrossRefGoogle ScholarPubMed
Laux, G, Heeg, B, van Hout, BA, Mehnert, A. Costs and effects of long acting risperidone compared with oral atypical and conventional depot formulations in Germany. Pharmacoeconomics 2005;23 (Suppl 1):49–61.Google ScholarPubMed
Li, Z, Ichikawa, J, Dai, J, Meltzer, HY. Aripiprazole a novel antipsychotic drug, preferentially increases dopamine release in the prefrontal cortex and hippocampus in rat brain. Eur J Pharmacol 2004;493(l–3):75–83.Google ScholarPubMed
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(12): 1209–23.CrossRefGoogle ScholarPubMed
Marder, S, Kramer, M, Ford, L, Eerdekens, E, Lim, P, Eerdekens, M. A 6 week, US-based, placebo-controlled study on the efficacy and tolerability of two fixed dosages of oral paliperidone extended-release tablets in the treatment of acute schizophrenia. Schizophr Res 2006;8(Suppl 1):56.Google Scholar
Marder, SR, Glynn, SM, Wirshing, WC, Wirshing, DA, Ross, D, Widmark, C, et al. Maintenance treatment of schizophrenia with risperidone or haloperidol: 2-year outcomes. Am J Psychiatry 2003;160(8):1405–12.CrossRefGoogle ScholarPubMed
Meltzer, HY. The mechanism of action of novel antipsychotic drugs. Schizophr Bull 1991; 17(2):263–87.CrossRefGoogle ScholarPubMed
Meltzer, HY, Lee, MA, Ranjan, R, Mason, EA, Cola, PA. Relapse following clozapine withdrawal: effect of neuroleptic drugs and cyproheptadine. Psychopharmacology (Berl) 1996; 124(1–2):176–87.CrossRefGoogle ScholarPubMed
Meltzer, HY, Li, Z, Kaneda, Y, Ichikawa, J. Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2003;27(7):1159–72.CrossRefGoogle ScholarPubMed
Moller, HJ, Llorca, PM, Sacchetti, E, Martin, SD, Medori, R, Parellada, E. Efficacy and safety of direct transition to risperidone longacting injectable in patients treated with various antipsychotic therapies. Int Clin Psychopharmacol 2005;20(3): 121–30.CrossRefGoogle Scholar
Moore, H, West, AR, Grace, AA. The regulation of forebrain dopamine transmission: relevance to the pathophysiology and psychopathology of schizophrenia. Biol Psychiatry 1999;46(1):40–55.CrossRefGoogle ScholarPubMed
Nordstrom, AL, Farde, L. Plasma prolactin and central D2 receptor occupancy in antipsychotic drug-treated patients. J Clin Psychopharmacol 1998;18(4):305–10.CrossRefGoogle ScholarPubMed
Nyberg, S, Farde, L, Halldin, C, Dahl, ML, Bertilsson, L. D2 dopamine receptor occupancy during low-dose treatment with haloperidol decanoate. Am J Psychiatry 1995;152(2):173–8.Google ScholarPubMed
Pierre, JM. Extrapyramidal symptoms with atypical antipsychotics: incidence, prevention and management. Drug Saf 2005;28(3):191–208.CrossRefGoogle ScholarPubMed
Remington, G, Mamo, D, Labelle, A. A PET study evaluating dopamine D2 receptor occupancy for long-acting risperidone. Am J Psychiatry 2006;163(3):396–401.CrossRefGoogle Scholar
Scherer, J, Tatsch, K, Schwarz, J, Oertel, WH, Konjarczyk, M, Albas, M. D2-dopamine receptor occupancy differs between patients with and without extrapyramidal side effects. Acta Psychiatr Scand 1994;90(4):266–8.CrossRefGoogle ScholarPubMed
Schooler, NR. Relapse and rehospitalization: comparing oral and depot antipsychotics. J Clin Psychiatry 2003;64(Suppl. 16): 14–7.Google ScholarPubMed
Schotte, A, Janssen, PF, Gommeren, W, Luyten, WH, Van, Gompel P, Lesage, AS, et al. Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl) 1996;124(l–2):57–73.CrossRefGoogle ScholarPubMed
Sedvall, G, Farde, L, Nyback, H, Pauli, S, Persson, A, Savic, I, et al. Recent advances in psychiatric brain imaging. Acta Radiol Suppl 1990;374:113–5.Google ScholarPubMed
Seeman, P. Atypical antipsychotics: mechanism of action. Can J Psychiatry 2002;47(l):27–38.CrossRefGoogle ScholarPubMed
Seeman, P. An update of fast-off dopamine D2 atypical antipsychotics. Am J Psychiatry 2005;162(10):1984–5.CrossRefGoogle ScholarPubMed
Seeman, P, Chau-Wong, M, Tedesco, J, Wong, K. Brain receptors for antipsychotic drugs and dopamine: direct binding assays. Proc Natl Acad Sci U S A 1975;72(ll):4376–80.CrossRefGoogle ScholarPubMed
Seeman, P, Corbett, R, Van Tol, HH. Atypical neuroleptics have low affinity for dopamine D2 receptors or are selective for D4 receptors. Neuropsychopharmacology 1997;16(2):93–110. discussion 1-35.CrossRefGoogle ScholarPubMed
Seeman, P, Tallerico, T. Rapid ralease of antipsychotic drugs from dopamine D2 receptors: an explanation for low receptor occupancy and early clinical relapse upon withdrawal of clozapine or quetiapine. Am J Psychiatry 1999; 156(6):876–84.CrossRefGoogle ScholarPubMed
Silvestri, S, Seeman, MV, Negrete, JC, Houle, S.-Shammi CM, Remington, GJ, et al. Increased dopamine D2 receptor binding after long-term treatment with antipsychotics in humans: a clinical PET study. Psychopharmacology (Berl) 2000;152(2):174–80.CrossRefGoogle ScholarPubMed
Snyder, S, Greenberg, D, Yamamura, HI. Antischizophrenic drugs and brain cholinergic receptors. Affinity for muscarinic sites predicts extrapyramidal effects. Arch Gen Psychiatry 1974;31(1):58–61.CrossRefGoogle ScholarPubMed
Strange, PG. Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects. Pharmacol Rev 2001 ;53(1): 119–33.Google ScholarPubMed
Takano, A, Sahara, T, Ikoma, Y, Yasuno, F, Maeda, J, Ichimiya, T, et al. Estimation of the time-course of dopamine D2 receptor occupancy in living human brain from plasma pharmacokinetics of antipsychotics. Int J Neuropsychopharmacol 2004;7(1): 19–26.CrossRefGoogle ScholarPubMed
Tamminga, CA, Carlsson, A. Partial dopamine agonists and dopaminergic stabilizers, in the treatment of psychosis. Curr Drug Targets CNS Neurol Disord 2002; 1 (2): 141–7.CrossRefGoogle ScholarPubMed
Tauscher, J, Jones, C, Remington, G, Zipursky, RB, Kapur, S. Significant dissociation of brain and plasma kinetics with antipsychotics. Mol Psychiatry 2002;7(3):317–21.CrossRefGoogle ScholarPubMed
Tauscher, J, Kufferle, B, Asenbaum, S, Tauscher-Wisniewski, S, Kasper, S. 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 (Berl) 2002; 162(1):42–9.CrossRefGoogle ScholarPubMed
Tauscher-Wisniewski, S, Kapur, S, Tauscher, J, Jones, C, Daskalakis, ZJ, Papatheodorou, G, et al. Quetiapine: an effective antipsychotic in first episode schizophrenia despite only transiently high dopamine-2 receptor blockade. J Clin Psychiatry 2002;63(ll):992–7.Google ScholarPubMed
Tollefson, G, Beasley, C, Tran, P, Street, J, Krueger, J, Tamura, R, 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(4):457–65.Google ScholarPubMed
Wirtstafter, D. Clozapine antagonizes the induction of striatal Fos expression by typical neuroleptics. Eur J Pharmacol 1998;358(3):Rl–3.Google Scholar
Xiberas, X, Martinot, JL, Mallet, L, Artiges, E, Loe, HC, Maziere, B, et al. Extrastriatal and striatal D(2) dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia. Br J Psychiatry 2001;179:503–8.CrossRefGoogle ScholarPubMed
Yokoi, F, Grunder, G, Biziere, K, Stephane, M, Dogan, AS, Dannals, RF, et al. Dopamine D2 and D3 receptor occupancy in normal humans treated with the antipsychotic drug aripiprazole (OPC 14597): a study using positron emission tomography and [llC]raclopride. Neuropsychopharmacology 2002;27(2):248–59.CrossRefGoogle Scholar
Young, CD, Bubser, M, Meltzer, HY, Deutch, AY. Clozapine pretreatment modifies haloperidol-elicited forebrain Fos induction: a regionally-specific double dissociation. Psychopharmacology (Berl) 1999; 144(3):255–63.CrossRefGoogle ScholarPubMed
Young, CL, Taylor, DM. Health resource utilization associated with switching to risperidone long-acting injection. Acta Psychiatr Scand 2006;114(1):14–20.CrossRefGoogle ScholarPubMed