Neutropenia olanzapine

The potential of lithium to prevent or treat clozapine-induced granulocytopenia has been reviewed (39). In a study of 38 patients on clozapine for schizophrenia or schizoaffective disorder, the addition of lithium increased the leukocyte count (42). A 20-year-old man with olanzapine-induced neutropenia 5 mg/day was able to tolerate 20 mg/day while taking lithium (43). 

Of 39 patients taking lithium, 18% had neutrophilia and 15% had raised activity of polymorphonuclear elas-tase (a marker of granulocyte activation) (345). In keeping with these observations, a chart review of 38 patients taking clozapine showed an increase in leukocyte count when lithium was added (42). A man with olanzapine-induced neutropenia (with a prior history of risperidone-induced neutropenia), which normalized with drug withdrawal, had no difficulty when the drug was reintroduced after the patient had been treated with lithium (43). 

Gajwani P, Tesar GE. Olanzapine-induced neutropenia. Psychosomatics 2000 41(2) 150-1. 

A 45-year-old woman developed neutropenia after taking clozapine 500 mg/day for 6 years combined with other agents (olanzapine 10 mg/day, benzopril hydrochloride 20 mg/day, and haloperidol 150 mg/ day) (154). Clozapine was withdrawn immediately and the granulocytes recovered within a few days. However, 10 weeks later clozapine was restarted and there was no recurrence over more than 3 years. 

Although hemotoxicity was not observed during premarketing studies of olanzapine (202), cases of neutropenia (neutrophil count below 1.5 x 109/1) (203) or agranulocytosis (neutrophil count below 0.5 x 109/1) (204) have been published. 

Neutropenia occurred in a 21-year-old man taking olanzapine 20 mg/day, haloperidol 10 mg/day, and lor-azepam 2 mg/day (208). The white cell count was 2.6 x 109/1, with a 22% differential neutrophil count. 

In three cases of leukopenia with olanzapine, a reduction in dose was followed by normalization of the leukocyte count and allowed continued treatment (210). Two of the patients had a previous history of neutropenia and agranulocytosis associated with typical neuroleptic drugs and the third developed neutropenia for the first time while taking olanzapine. 

Of two cases of olanzapine-induced neutropenia, one occurred 17 days after the first dose of olanzapine and the other more than 5 months after the first dose (203) in the second patient, re-exposure to olanzapine caused the neutrophil count to fall again. In neither case was there evidence of infection, and the white blood cell counts increased immediately to the reference ranges after withdrawal of olanzapine, no special treatment being necessary. In addition, two cases of reversible leukopenia during treatment with olanzapine have also been reported (211). 

In a 46-year-old man taking olanzapine 10 mg/day, leukopenia and neutropenia were associated with HLA types A1 24, B7, B35, DRB1 15, DRB1 11, DRB3 01-03, DRB5 01-02, a haplotype distinct from that previously observed in clozapine-induced hemo-toxicity (213). 

In a 31-year-old woman clozapine monotherapy 75 mg/day caused neutropenia (neutrophil count 1.1 x 109/1) 5 days after clozapine withdrawal the neutrophil count normalized (2.6 x 109/1). Olanzapine was then introduced at 5 mg/day and the next day increased to 10 mg/day. After a week the neutrophil count fell to 0.9 x 109/1 and olanzapine was withdrawn. The neutrophil count was normal 4 weeks after olanzapine withdrawal. 

Prolonged granulocytopenia due to olanzapine occurred in a 39-year-old woman after clozapine withdrawal (217). In contrast, two patients with severe clozapine-induced granulocytopenia and agranulocytosis were successfully treated with olanzapine in a dose greater than 25 mg/ day (218). Furthermore, a 65-year-old man who had previously developed leukopenia and neutropenia, first with clozapine and then also with risperidone, took olanzapine (20 mg/day for 2 years with only a transient reduction in leukocyte and neutrophil (but not erythrocyte or platelet) counts) during a flu-like illness (219). 

Steinwachs A, Grohmann R, Pedrosa F, Ruther E, Schwerdtner I. Two cases of olanzapine-induced reversible neutropenia. Pharmacopsychiatry 1999 32(4) 154-6. 

Duggal HS, Gates C, Pathak PC. Olanzapine-induced neutropenia mechanism and treatment. J Clin... 

Abdullah N, Voronovitch L, Taylor S, Lippmann S. Olanzapine and haloperidol potential for neutropenia Psychosomatics 2003 44 83-4. 

Benedetti F, Cavallaro R, Smeraldi E. Olanzapine-induced neutropenia after clozapine-induced neutropenia. Lancet 1999 354(9178) 567. 

Haematologic A case report of valproic add-related anticonvulsant hypersensitivity syndrome and subsequent olanzapine-related neutropenia and thrombocytopenia is described [177 ]. A case of a 23-year-old male who developed olanzapine-associated leucopenia and thrombocytopenia after a previous history of leucopenia with clozapine is reported [178 ]. 

A 27-year-old woman taking VPA and olanzapine developed a hypersensitivity syndrome consisting of diffuse rash with elevated liver enzymes, which resolved after VPA was discontinued. She subsequently developed neutropenia and thrombocytopenia. The authors suggested that both the hypersensitivity and the neutropenia/ thrombocytopenia may be due to drug interaction between VPA and olanzapine [197 ]. 

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