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Psychopharmacology of olanzapine

A review

Published online by Cambridge University Press:  06 August 2018

C. M. E. Stephenson*
Affiliation:
Institute of Psychiatry, London
L. S. Pilowsky
Affiliation:
Institute of Psychiatry, London
*
Correspondence: Dr C. M. E. Stephenson, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SES 8AF

Extract

The development of atypical antipsychotics has revolutionised the treatment of schizophrenia, as well as providing new insights into its cause. The archetypal atypical antipsychotic is clozapine, which has therapeutic advantages over traditional antipsychotics, as well as a low potential for producing extrapyramidal side-effects (EPS) (Kane et al, 1988). However, clozapine causes agranulocytosis in 1% of patients, and there has consequently been a search for novel atypical antipsychotics, as efficacious as clozapine, but without the need for intensive blood monitoring. There has been much discussion of the definition and characteristics of an atypical antipsychotic drug, and an operational understanding seems to have been agreed upon, that atypical drugs have therapeutic efficacy in treating schizophrenia, without producing EPS (Deutch et al, 1991; Kerwin, 1994).

Type
Research Article
Copyright
Copyright © 1999 The Royal College of Psychiatrists 

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References

Andreasen, N. C. (1981) Scale for the Assessment of Negative Symptoms (SANS). Iowa City, IA: University of Iowa.Google Scholar
Bakshi, V. P. & Geyer, M. A. (1995) Antagonism of phencyclidine-induced deficits in prepulse inhibition by the putative atypical antipsychotic olanzapine. Psychopharmacology, 122, 198201.CrossRefGoogle ScholarPubMed
Baldacchino, A. M., Stubbs, J. H. & Nevison-Andrews, D. (1997) The use of olanzapine in non-compliant or treatment-resistant clozapine population in hospital. Pharmaceutical Journal, 260, 207209.Google Scholar
Baldwin, D. S. & Montgomery, S. A. (1995) First clinical experience with olanzapine (LY 170053): results of an open-label safety and dose-ranging study in patients with schizophrenia. International Clinical Psychopharmacology, 10, 239244.CrossRefGoogle ScholarPubMed
Beasley, C. M. Jr., Sanger, T., Saterlee, W., et al (1996a) Olanzapine vs placebo: results of a double-blind fixed dose olanzapine trial. Psychopharmacology (Berlin), 124, 159167.CrossRefGoogle Scholar
Beasley, C. M., Tollefson, G., Tran, P., et al (1996b) Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology, 14, 111123.CrossRefGoogle ScholarPubMed
Beasley, C. M., Tollefson, G., Tran, P. (1997a) Efficacy of olanzapine: an overview of pivotal clinical trials. Journal of Clinical Psychiatry, 58 (suppl. 10), 712.Google ScholarPubMed
Beasley, C. M., Tollefson, G., Tran, P. (1997b) Safety of olanzapine. Journal of Clinical Psychiatry, 58 (suppl. 10), 1317.Google ScholarPubMed
Beasley, C. M., Hamilton, S. Y., Crawford, A. M., et al (1997c) and the Olanzapine E003 Study Group Olanzapine versus haloperidol: acute phase results of the international double-blind olanzapine trial. European Neuropsychopharmacology, 7, 125137.CrossRefGoogle Scholar
Bergstrom, R. F., Callaghan, J. T., Cerimele, B. J., et al (1995) Pharmacokinetics of olanzapine in elderly and young (abstract). Pharmaceutical Research, 12 (suppl.), S358.Google Scholar
Boyd, D., Obermeyer, B. D., Nyhart, E. H. Jr., et al (1993) The disposition of olanzapine in healthy volunteers (abstract no. 120). Pharmacologist, 35, 176.Google Scholar
Bymaster, F. P., Calligaro, D. O., Falcone, J. F., et al (1996a) Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology, 14, 8796.CrossRefGoogle ScholarPubMed
Bymaster, F. P., Hemrick-Luecke, S. K., Perry, K. W., et al (1996b) Neurochemical evidence for antagonism by olanzapine of dopamine, serotonin, α1-adrenergic and muscarinic receptors in vivo in rats. Psychopharmacology, 124, 8794.CrossRefGoogle Scholar
Bymaster, F. P., Rasmussen, K., Calligaro, D. O., et al (1997) In vitro and in vivo biochemistry of olanzapine: a novel, atypical antipsychotic drug. Journal of Clinical Psychiatry, 58 (suppl. 10), 2836.Google ScholarPubMed
Chiodo, L. A. & Bunney, B. S. (1983) Typical and atypical neuroleptics: differential effects of chronic administration on the activity of A9 and A10 midbrain dopaminergic neurons. Journal of Neuroscience, 3, 16071619.CrossRefGoogle ScholarPubMed
Cools, A. R., Prinssen, E. P. M. & Ellenbroek, B. A. (1995) The olfactory tubercle as a site of action of neuroleptics with an atypical profile in the paw test: effect of risperidone, prothiphendyl, ORG 5222, sertindole, olanzapine. Psychopharmacology, 119, 428439.CrossRefGoogle ScholarPubMed
Corbett, R., Camacho, F., Woods, A. T., et al (1995) Antipsychotic agents antagonize non-competitive N-methyl-D-aspartate antagonist-induced behaviours. Psychopharmacology, 120. 6774.CrossRefGoogle Scholar
Deutch, A. Y., Moghaddam, B., Innis, R. B., et al (1991) Mechanisms of action of atypical antipsychotic drugs. Schizophrenia Research, 4, 121156.CrossRefGoogle ScholarPubMed
Deutch, A. Y., Lee, M. C. & ladarola, M. J. (1992) Regionally specific effects of atypical antipsychotic drugs on striatal fos expression: the nucleus accumbens shell as a locus of antipsychotic action. Molecular and Cellular Neuroscience, 3, 32341.CrossRefGoogle ScholarPubMed
Dragunow, M., Robertson, G. S., Faull, R. L. M., et al (1992) D2 dopamine receptor antagonists induce fos and related proteins in rat striatal neurons. Proceedings of the National Academy of Sciences of the United States of America, 89, 42704272.Google Scholar
Endicott, J., Spitzer, R. L., Fleiss, J. L., et al (1976) The Global Assessment Scale: A procedure for measuring overall severity of psychiatric disturbances. Archives of General Psychiatry, 33, 766771.CrossRefGoogle Scholar
Fink-Jensen, A., Ludvigsen, T. S. & Korsgaard, N. (1995) The effect of clozapine on fos protein immunoreactivity in the rat forebrain is not mimicked by the addition of α1-adrenergic or 5-HT2 receptor blockade to haloperidol. Neuroscience Letters, 194, 7780.CrossRefGoogle ScholarPubMed
Fuller, R. W. & Snoddy, H. D. (1992) Neuroendocrine evidence for antagonism of serotonin and dopamine receptors by olanzapine, an antipsychotic drug candidate. Research Communications in Chemical Pathology and Pharmacology, 77, 8793.Google ScholarPubMed
Gleason, S. D. & Shannon, H. E. (1997) Blockade of phencyclidine-induced hyperlocomotion by olanzapine, clozapine, and serotonin receptor subtype selective antagonists in mice. Psychopharmacology, 129, 7984.CrossRefGoogle ScholarPubMed
Guy, W. (1976) ECDEU Assessment Manual for Psychopharmacology (Revised DHEW Pub. (ADM)). Rockville, MD: National Institute for Mental Health.Google Scholar
Kane, J. M., Honigfeld, G., Singer, J., Meltzer, H. & the Clozaril Collaborative Study Group (1988) Clozapine for the treatment resistant schizophrenic. Archives of General Psychiatry, 45, 789796.CrossRefGoogle ScholarPubMed
Kapur, S. & Remington, G. (1996) Serotonin-dopamine interaction and its relevance to schizophrenia. American Journal of Psychiatry, 153, 466476.Google ScholarPubMed
Kassahun, K., Mattiuz, E., Nyhart, E. Jr, et al (1997) Disposition and biotransformation of the antipsychotic agent olanzapine in humans. Drug Metabolism and Disposition, 25, 8193.Google Scholar
Kay, S. R., Fiszbein, A., Opler, L. A. (1987) The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophrenia Bulletin, 13, 261276.CrossRefGoogle ScholarPubMed
Kerwin, R. W. (1994) The new atypical antipsychotics. British Journal of Psychiatry, 164, 141148.CrossRefGoogle ScholarPubMed
Launer, M. A. (1997) High dose olanzapine in treatment resistant schizophrenia. Schizophrenia Research, 29, 150.Google Scholar
Lieberman, J. A. (1996) Atypical antipsychotic drugs as a first-line treatment of schizophrenia: a rationale and hypothesis. Journal of Clinical Pharmacology, 57 (suppl. 11), 6871.Google ScholarPubMed
Martin, J., Gomez, J.-C., Garcia-Bernado, E., et al (1997) Olanzapine in treatment-refractory schizophrenia: results of an open-label study The Spanish Group for the Study of Olanzapine in Treatment-Refractory Schizophrenia. Journal of Clinical Psychiatry, 58, 479483.CrossRefGoogle Scholar
Maurel-Remy, S., Audinot, V., Lejeune, F., et al (1995) Blockade of phencyclidine induced hyperlocomotion in rats by clozapine, MDL 100907 and other antipsychotics correlates with affinity at 5-HT2A receptors. British Journal of Pharmacology, 114, 153P.Google Scholar
Montgomery, S. A. & Asberg, M. (1979) A new depression scale designed to be sensitive to change. British Journal of Psychiatry, 134, 382389.CrossRefGoogle ScholarPubMed
Moore, N. A., Tye, N. C., Axton, M. S., et al (1992) The behavioural pharmacology of olanzapine, a novel “atypical” antipsychotic agent. Journal of Pharmacology and Experimental Therapeutics, 262, 545551.Google Scholar
Moore, N. A., Calligaro, D. O., Wong, D. T., et al (1993) The pharmacology of olanzapine and other new antipsychotic agents. Current Opinion in Investigational Drugs, 2, 281293.Google Scholar
Moore, N. A., Leander, D., Benvenga, M. J., et al (1997) Behavioural pharmacology of olanzapine: a novel antipsychotic drug. Journal of Clinical Psychiatry, 58 (suppl. 10), 3744.Google Scholar
Nyberg, S., Farde, L. & Halldin, C. (1997) A PET study of 5-HT2 and D2 dopamine receptor occupancy induced by olanzapine in healthy subjects. Neuropsychopharmacology, 16, 7884.CrossRefGoogle ScholarPubMed
Overall, J. & Gorman, D. E. (1962) The Brief Psychiatric Rating Scale. Psychological Reports, 10, 799812.CrossRefGoogle Scholar
Patel, B. R., Nyhart, E. L. Jr., Callaghan, J. T., et al (1995) Combined population pharmacokinetic analysis of olanzapine in healthy volunteers (abstract). Pharmaceutical Research, 12 (suppl.), S360.Google Scholar
Pilowsky, L. S., Costa, D. C., Ell, P. J., et al (1992) Clozapine, single photon emission tomography and the D2 dopamine receptor blockade hypothesis of schizophrenia. Lancet, 340, 199202.CrossRefGoogle ScholarPubMed
Pilowsky, L. S., Busatto, G. F., Taylor, M., et al (1996) Dopamine D2 receptor occupancy in vivo by the novel atypical antipsychotic olanzapine – a l23l IBZM single photon emission tomography (SPET) study. Psychopharmacology, 124, 148153.CrossRefGoogle Scholar
Pilowsky, L. S., Mulligan, R. S., Acton, P. D., et al (1997) Limbic selectivity of clozapine. Lancet, 350, 490491.CrossRefGoogle ScholarPubMed
Ratakonda, S., Miller, C. E., Gorman, J. M. & Sharif, Z. A. (1997) Efficacy of a 12 week trial of olanzapine in treatment refractory schizophrenia or schizoaffective disorder. Schizophrenia Research, 29, 150.CrossRefGoogle Scholar
Ring, B. J., Catlow, J., Lindsay, T. J., et al (1996a) Identification of the human cytochromes P450 responsible for the in vitro formation of the major oxidative metabolites of the antipsychotic agent olanzapine. Journal of Pharmacology and Experimental Therapeutics, 276, 658666.Google ScholarPubMed
Ring, B. J., Binkley, S. N., Vanderbranden, M., et al (1996b) In vitro interaction of the antipsychotic agent olanzapine with human cytochromes P450 CYP2C9, CYP2CI9, CYP2D6 and CYP3A. British Journal of Clinical Pharmacology, 41, 181186.CrossRefGoogle Scholar
Robertson, G. S. & Fibiger, H. C. (1992) Neuroleptics increase c-fos expression in the forebrain: contrasting effects of haloperidol and clozapine. Neuroscience, 46, 315328.CrossRefGoogle ScholarPubMed
Robertson, G., Matsamura, H. & Fibiger, H. C. (1994) Induction patterns of fos-like immunoreactivity in the forebrain as predictors of atypical antipsychotic activity. Journal of Pharmacology & Experimental Therapeutics, 271, 10581066.Google ScholarPubMed
Robertson, G. & Fibiger, H. C. (1996) Effects of olanzapine on regional c-fos expression in rat forebrain. Neuropsychopharmacology, 14, 105110.CrossRefGoogle ScholarPubMed
Schlicker, E. & Marr, I. (1996) The moderate affinity of clozapine at H3 receptors is not shared by its two major metabolites and by structurally related and unrelated atypical neuroleptics. Naunyn Schmiedebergs Archives of Pharmacology (Berlin), 353, 290294.CrossRefGoogle Scholar
Sheitman, B. B., Lindgren, J. C., Early, R. R H., et al (1997) High-dose olanzapine for treatment-refractory schizophrenia. American Journal of Psychiatry, 154, 1626.CrossRefGoogle ScholarPubMed
Stockton, M. E. & Rasmussen, K. et al (1996) Electrophysiological effects of olanzapine, a novel atypical antipsychotic, on A9 and AIO dopamine neurons. Neuropsychopharmacology, 14, 97104.CrossRefGoogle Scholar
Tollefson, G., Beasley, C. M. Jr, Tamura, R. N., et al (1997a) Blind, controlled, long-term study of the comparative incidence of treatment-emergent tardive dyskinesia with olanzapine or haloperidol. American Journal of Psychiatry, 154, 12481254.Google ScholarPubMed
Tollefson, G., Beasley, C. M. Jr, & Tran, P. (1997b) Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. American Journal of Psychiatry, 154, 457465.Google ScholarPubMed
Tran, P. V., Dellva, M. A. & Tollefson, G. D. (1998) Oral olanzapine versus oral haloperidol in the maintenance treatment of schizophrenia and related psychoses. British Journal of Psychiatry, 172, 499505.CrossRefGoogle ScholarPubMed
Tollefson, G., Beasley, C. M. Jr, Tamura, R. N. et al (1997a) Extrapyramidal symptoms and tolerability of olanzapine versus haloperidol in the acute treatment of schizophrenia. Journal of Clinical Psychiatry, 58, 205211.Google Scholar
Tollefson, G., Hamilton, S. H., Kuntz, A. J., et al (1997b) Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders. Journal of Clinical Psychopharmacology, 17, 407418.Google Scholar
Travis, M. J., Busatto, G. F., Pilowsky, L. S., et al (1997) Serotonin 5-HT2a occupancy in vivo and response to the new atypical antipsychotics olanzapine and sertindole (letter). British Journal of Psychiatry, 171, 290291.CrossRefGoogle Scholar
Weaver, M. G. (1997) Olanzapine – pharmacology and clinical evaluation of a new atypical antipsychotic. Journal of Serotonin Research, 4, 145157.Google Scholar
White, F. J. & Wang, R. Y. (1983) Differential effects of classical and atypical antipsychotic drugs on A9 and A10 dopamine neurons. Science, 221, 10541057.CrossRefGoogle ScholarPubMed
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