Human leukocyte antigen typing, response to neuroleptics, and clozapine-induced agranulocytosis in Jewish Israeli schizophrenic patients

Citation
S. Meged et al., Human leukocyte antigen typing, response to neuroleptics, and clozapine-induced agranulocytosis in Jewish Israeli schizophrenic patients, INT CLIN PS, 14(5), 1999, pp. 305-312
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology,"Neurosciences & Behavoir
Journal title
INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY
ISSN journal
0268-1315 → ACNP
Volume
14
Issue
5
Year of publication
1999
Pages
305 - 312
Database
ISI
SICI code
0268-1315(199909)14:5<305:HLATRT>2.0.ZU;2-K
Abstract
The atypical antipsychotic agent clozapine is known to be effective in schi zophrenic patients refractory to other medications; however, it induces agr anulocytosis in approximately 1-2%. In Jews, this complication is associate d with the haplotype HLA B38, DR4, DQ3. The aim of the present study was to determine which human leukocyte antigen (HLA) antigens are involved in clo zapine-induced agranulocytosis. We performed HLA typing in 88 Jewish Israel i schizophrenic patients and in 127 ethnically matched healthy individuals. Thirty eight patients responsive to standard antipsychotic medications wer e treated with haloperidol, and 50 refractory patients received clozapine. A trend was noted for elevated rates of HLA B38 among control individuals a nd clozapine-treated patients of Ashkenazi origin compared to individuals o f non-Ashkenazi origin, but the findings failed to reach statistical signif icance. No association was found between HLA class I antigens and the respo nse to haloperidol or clozapine. Neutropenia developed in two clozapine-tre ated patients and agranulocytosis in one. Two of these three patients were of Ashkenazi origin, and both demonstrated the HLA B38 phenotype. Although the findings did not reach a statistical significance because of the small number of patients, they may support an association between clozapine-induc ed neutropenia/agranulocytosis and Ashkenazi origin and the HLA B38 phenoty pe. The rate of agranulocytosis in our sample (2%) is similar to the usual cumulative risk of agranulocytosis but in contrast to its high frequency am ong Jewish American patients. One possible explanation for this difference is the high rate of Ashkenazi patients in the American sample and the prepo nderance of non-Ashkenazi patients in our population. Int Clin Psychopharma col 14:305-312 (C) 1999 Lippincott Williams & Wilkins.