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Fatal neutropenia and thrombocytopenia asso- ciated with ticlopidine. Ann Pharmacother 1994;28:1236-8. 12. Nand S. Bayer R. Prinz RA. Felten W. Godwin JE. Granulocyte- macrophage colony stimulating factor for the treatment of drug induced agranulocytosis. AmJ Hernatoll99I;37:267-9. 13. Ruiz-IrastorzaG, AJonso JJ. Iglesias JJ. Aguirre C. Granulocyte colony- stimulating factor for neutropenia secondary to ticlopidine. Acta Haema- toll994;91:106-7. 14. Elis A, Lishner M. Lang R. Ravid M. Agranulocytosis associated with enalapril. DICP Ann Pharmacother 1991;25:461-2. SUSPECTED NEUROLEPTIC MALIGNANT SYNDROME IN A PATIENT RECEIVING CLOZAPINE Luba Ganelin, Pesach S Lichtenberg, Esther-Lee Marcus, and R Gabriel Munter OBJECTIVE: To report a case of suspected neuroleptic malignant syndrome (NMS) associated with clozapine therapy. CASE SUMMARY: A 42-year-old schizophrenic man treated with clozapine developed a temperature of 39.5 ·C, diaphoresis, tachycardia, rigidity, and leukocytosis. His serum creatine kinase concentration was 25 000 UIL. A diagnosis of NMS was made. He was treated with bromocriptine and supportive therapy, and recovered within a week. DISCUSSION: Despite earlier expectations that c1ozapine, with a pharmacologic profile differing from that of other antipsychotic medications, might not cause NMS, NMS remains the most likely diagnosis in this case. CONCLUSIONS: NMS may be a possible complication of clozapine therapy. Ann Pharmacother 1996;30:248-50. TYPICAL ANTIPSYCHOTIC MEDICATIONexerts its effect through blockade of the dopamine type 2 (Dz)-receptor. The same mechanism underlies the high incidence of extrapyramidal adverse effects seen with these medications. I A potentially life-threatening complication of antipsychotic medication is neuroleptic malignant syndrome (NMS). NMS is char- acterized by hyperthermia, autonomic disturbances, neuro- Luba Ganelin MD. Senior Physician. Department of Psychiatry. Herzog Hospital. Jerusalem. Israel Pesach S Lichtenberg MD. Lecturer in Psychiatry. Hadassah Hospital-Hebrew Uni- versity. Chief of Psychiatry Department A. Herzog Hospital. POB 35300. Jerusalem 91351. Israel. FAX 972-2-536075 Esther-Lee Marcus MD. Senior Physician. Department of Geriatrics. Herzog Hos- pital R Gabriel Munter MD. Resident. Department of Internal Medicine. Shaare-Zedek Medical Center. Jerusalem, Israel Reprints: Pesach S Lichtenberg MD muscular rigidity, changes in mental status, and elevated concentrations of serum creatine kinase (CK).2-S This syn- drome has been attributed to dopamine blockade, especial- ly of the Dj-receptors." The introduction of clozapine, an atypical antipsychotic agent virtually devoid of classical extrapyramidal adverse effects.v raised hopes that NMS could be avoided. Cloza- pine has a unique pharmacologic profile, demonstrating a higher affinity for the D I receptor and a higher DiDz-re- ceptor binding ratio than is the case for typical antipsychot- ic agents." The drug has a high affinity to serotonergic, muscarinic, and adrenergic receptors." Early case reports describing NMS with clozapine thera- py involved the concomitant administration of other drugs." More recently, however, seven cases of NMS associated with clozapine monotherapy have been reported.P'? Nev- ertheless, questions remain for each of those cases con- cerning the accuracy of the diagnosis and whether clozap- ine was the causative agent." We describe another suspect- ed case of NMS in a patient treated with clozapine. CASE REPORT A 42-year-old Israeli-born man of Iraqi Jewish origin was diag- nosed with paranoid schizophrenia at age 14 years. His paranoid ideation and consequent violent behavior led over the years to 37 hospitalizations, during which he received adequate trials of a wide variety of antipsychotic medications, including haloperidol, perphenazine, chlorpromazine, trifluoperazine, and thioridazine, at what are considered therapeutic dosages. The effect of these treatments on his psychosis was limited at best. During one of his earlier hospitalizations, 6 years before the current episode, he developed NMS while receiving oral haloper- idol 60 mg/d and methotrimeprazine 300 mg/d. The NMS was characterized by a temperature of 40.5 ·C, rigidity, autonomic 248 • The Annals of Pharmacotherapy • 1996 March. Volume 30