Clozapine in schizophrenia

Masellis, M., Basile, V. S., Meltzer, H. Y. etal. (2001). Lack of association between theT->C 267 serotonin 5-HT 6 receptor gene (HTR6) polymorphism andprediction of response to clozapine in schizophrenia. Schizophr. Res., 15, 49-58. 

Masellis M, Basile V, Meltzer HY, Lieberman JA, Sevy S, Macciardi FM et al. Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenia patients. Neuropsychopharmacology 1998 19(2) 123—132. 

Masellis, M., Basile, V., Meltzer, H.Y., Lieberman, J.A., Sevy, S., Macciardi, EM., Cola, P., Howard, A., Badri, E, Nothen, M.M., Kalow, W., and Kennedy, J.L. (1998) Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenia patients. Neuropsychopharmacology 19 123-132. 

Evins AE, Fitzgerald SM, Wine L, Rosselli R, Goff DC. 2000. Placebo-controlled trial of glycine added to clozapine in schizophrenia. Am J Psychiatry 157 826-828. 

Goff DC, Leahy L, Berman I, Posever T, Herz L, et al. 2001. A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia. J Clin Psychopharmacol 21 484-487. 

Woodward ND, Jayathilake K, Meltzer HY (2007) COMT vaill08/158met genotype, cognitive function, and cognitive improvement with clozapine in schizophrenia. Schizophr Res 90 86-96... 

M. Masellis, V. Basile, H. Y. Meltzer, L. A. Lieberman, S. Sevy, F. M. Macciardi, P. Cola, A. Howard, F. Badri, M. M. Nothen, W. Kalow, and J. L. Kennedy, Serotonin subtype 2 receptor genes and chnical response to clozapine in schizophrenia patients. Neuropsychopharmacology 19 123-132 (1998). 

Your patient is prescribed clozapine for schizophrenia that has not responded to other drugs. You must discuss this new therapy with the family. Discuss what points to include in this family teaching session. 

Ginsberg G, Shani S, Lev B (1998). Cost-benefit analysis of risperidone and clozapine in the treatment of schizophrenia in Israel. Pharmacoeconomics 13,231—41. 

Meltzer FiY, Cola P, Way L, et al (1995). Cost effectiveness of clozapine in neuroleptic-resistant schizophrenia. Am J Psychiatry 150, 1630-8. 

Wahlbeck K, Cheine M, Essali A, Adams C (1999). Evidence of clozapine s effectiveness in schizophrenia a systematic review and metaanalysis of randomised trials. Am J Psychiatry 156, 990-9. 

Reference has been made already to the shortcomings of the term neuroleptic . We now have a situation in which the drugs that are most useful in schizophrenia are regarded as atypical. While the term was introduced to cover those neuroleptics that do not cause EPSs, it has become synonymous with clozapine which has additional advantages over other neuroleptics (e.g. reduces negative symptoms, see text). Thus it is not always clear what is meant or covered by atypical. Hopefully this distinction between the neuroleptics will become unnecessary as better compounds are developed and the older ones become obsolete. 

Certainly clozapine can avoid EPSs by only blocking a fraction of D2 receptors but that seems insufficient on its own to make clozapine so effective in schizophrenia. That is probably achieved by a unique combination of other blocking actions, at Di, D4, 5-HT2, o 2 and possibly other receptors (see Fig. 17.8). It may simply be that clozapine is so effective because it is so dirty , a view held for many years about the first neuroleptic chlorpromazine. Indeed it is unlikely that the varied symptoms of such a complicated disorder could be rectified by manipulating just one NT. 

Kohn, Y., Ebstein, R.P., Heresco-Levy, U., Shapira, B., Nemanov, L., Gritenko, I., Avnon, M., and Lerer, B. (1997) Dopamine D4 receptor gene polymorphisms relation to ethnicity., no association with schizophrenia and response to clozapine in Israeli subjects. Eur Neuropsychopharmacol, 7 39-43. 

Efficacy in short-term treatment. From studies in adult schizophrenia, it is evident that clozapine treatment has at least the same or superior antipsychotic effect, compared to typical antipsychotics. In some studies, clozapine was superior with regard to symptom reduction in severe and acute schizophrenic patients. As the guidelines do not allow the use of clozapine as a first-choice drug, most patients have been treated before with at least two atypical or typical antipsychotics. Only one controlled trial has assessed the efficacy of clozapine in child and adolescent psychiatry. In this study (Kumra et ah, 1996), clozapine was found to be superior to haloperidol in all measures of psychosis, and showed a striking superiority for both positive and negative symptoms. 

Frazier, J.A., Gordon, C.T., McKenna, K., Lenane, M.C., Jlh, D., and Rapoport, J.L. (1994) An open trial of clozapine In 11 adolescents with childhood-onset schizophrenia./ Am Acad Child Adolesc Psychiatry 33 658-663. 

Remschmidt, H., Schulz, E., and Mattin, M. (1994) An open trial of clozapine in thirty-six adolescents with schizophrenia. / Child Adolesc Psychopharmacol 4 31-41. 

Turetz, M., Mozes, T, Toren, P., Chernauzan, N., Yoran-Hegesh, R., Mester, R., Wittenberg, N., Tyano, S., and Weizman, A. (1997) An open trial of clozapine in neuroleptic-resistant childhood-onset schizophrenia. Br J Psychiatry 170 507-510. 

McElroy SL, Keck PE Jr, Pope EIG Jr, et al Valproate in primary psychiatric disorders literature review and clinical experience in a private psychiatric hospital, in Use of Anticonvulsants in Psychiatry Recent Advances. Edited by McElroy SL, Pope HG Jr. Clifton, NJ, Oxford Health Care, 1988b McElroy SL, Keck PE Jr, Pope HG Jr, et al Valproate in the treatment of rapid-cycling bipolar disorder. J Clin Psychopharmacol 8 275-279, 1988c McElroy SL, Sessain EC, Pope HG Jr, et al Clozapine in the treatment of psychotic mood disorders, schizoaffective disorder and schizophrenia. J Clin Psychiatry 52 411-414, 1991a... 

DasGupta K, Young A Clozapine-induced neuroleptic malignant syndrome. J Clin Psychiatry 52 105-107, 1991 Davis KL, Kahn RS, Ko G, et al Dopamine in schizophrenia a review and reconceptualization. Am J Psychiatry 148 1474-1486, 1991 Devinsky O, Honigfeld G, Patin J Clozapine-related seizures. Neurology 41 369-371, 1991... 

Meltzer, H.Y., Alphs, L., Green, A.I., et al. Clozapine treatment for suicidality in schizophrenia International Suicide Prevention Trial flhterSePT). Arch. Gen. Psychiatry 60(1), 82-91, 2003. 

Rosenheck, R, Cramer, J., Xu, W., et al.. A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia Department of Veterans Affairs Co-operative Study Group on clozapine in refractory schizophrenia. N. Engl. J. Med. 337, 809-815. 1997. 

Kapur S, Zipursky RB, Remington G. Clinical and theoretical implications of 5-HT 2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia. Am J Psychiatry 1999 156 286-293. 

Rosenheck R, Dunn L, Peszke M, et al. Impact of clozapine on negative symptoms and on the deficit syndrome in refractory schizophrenia. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia. Am J Psychiatry 1999 156 88-93. 

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