Leukopenia clozapine

Discontinuation - In the event of planned termination of clozapine therapy, gradual reduction in dose is recommended over a 1- to 2-week period. However, should a patient s medical condition require abrupt discontinuation (eg, leukopenia), carefully observe for the recurrence of psychotic symptoms and symptoms related to cholinergic rebound (eg, headache, nausea, vomiting, diarrhea). After the discontinuation of clozapine, continue weekly WBC counts for an additional 4 weeks. 

Clozapine was the first atypical antipsychotic released in the United States. However, clozapine is associated with the risk of leukopenia and, potentially, lethal agranulocytosis. Because of these concerns, hematological monitoring during clozapine pharmacotherapy is required (Alphs and Anand, 1999). Due to these hematological risks, clozapine is indicated only for patients with treatment-resistant schizophrenia. The other atypical antipsychotics, risperidone, olanzapine, quetiapine, and ziprasidone, that are marketed in the United States can be used as first-line treatments for adults with schizophrenia. 

Hematological Agranulocytosis, leukopenia, neutropenia N/A Complete blood count with differential at baseline and if symptoms of infection, pallor, or bruising develop shortly after treatment initiation White blood counts weekly for 6 months, then every other week thereafter if treated with clozapine... 

Clozapine also has been shown to benefit schizoaffective and bipolar patients with treatment-refractory mania ( 54) patients with Parkinson s disease and those with other neurological disorders with psychoses, such as Huntington s disease. Although clozapine has been shown to be an effective agent in the elderly, its usefulness in this population is limited because of its anticholinergic, sedative, cardiovascular, and potentially toxic effects on the bone marrow ( 55). In a study of 12 elderly female psychotic patients on clozapine (maximal daily dose, 300 mg), for example, five were taken off clozapine because of postural hypotension, one had a nonfatal episode of agranulocytosis, and one had leukopenia ( 56). 

George TP, Innamorato L, Sernyak MJ, Baldessarini RJ, Centorrino F. Leukopenia associated with addition of paroxetine to clozapine. J Clin Psychiatry 1998 59(1) 31. 

Seizures and other neurological effects have been described in a few cases when lithium was added to clozapine (626), but in other instances the combination was beneficial in overcoming treatment resistance or attenuating clozapine-induced leukopenia. Five treatment-resistant patients were treated successfully with a combination of clozapine and lithium with no clinically significant adverse events (627). However, a 59-year-old woman developed neurotoxic symptoms 3 days after lithium was added to clozapine the symptoms resolved when both drugs were stopped and recurred with rechallenge (628). 

Patients with aggressive schizophrenia (n = 29) improved when treated with clozapine one was withdrawn after the development of leukopenia. In 10 mentally retarded patients taking clozapine for 15 days to 46 months improvement was observed. Half of the patients developed sedation and hypersalivation, and one discontinued the drug after 2 weeks because of neutropenia. The putative neurotoxicity of clozapine in moderately to... 

Clozapine has been used to treat psychosis related to Parkinson s disease (SEDA-22,57) (78). In a randomized, double-blind, placebo-controlled trial of low doses of clozapine (6.25-50 mg/day) in 60 patients (mean age 72 years) with idiopathic Parkinson s disease and drug-induced psychosis, the patients in the clozapine group had significantly more improvement after 14 months than those in the placebo group in all measures used to determine the severity of psychosis (80). Clozapine improved tremor and had no deleterious effect on the severity of parkinsonism, but in one patient it was withdrawn because of leukopenia. 

Leukopenia has been reported after combination treatment with two leukopenic agents, clozapine and topiramate (307). 

Behar D, Schaller JL. Topiramate leukopenia on clozapine. Eur Child Adolesc Psychiatry 2004 13 51-2. 

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). 

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). 

Seizures and other neurological effects have been described in a few cases when lithium was added to clozapine (204), but in other instances the combination was beneficial in overcoming treatment resistance or attenuating clozapine-induced leukopenia. 

Blood Dyscrasias Mild leukocytosis, leukopenia, and eosinophilia occasionally occur with antipsychotic treatment, particularly with clozapine and less often with phenothiazines of low potency. It is difficult to determine whether leukopenia that develops during the administration of such agents is a forewarning of impending agranulocytosis. This serious comphcation occurs in not more than 1 in 10,000 patients receiving chlorpromazine or other low-potency agents (other than clozapine) it usually appears within the first 8-12 weeks of treatment. 

Hematologic Agranulocytosis, leukopenia, and neutropenia associated with clozapine have been extensively studied and discussed [SED-15, 829 SEDA-32, 97]. 

Immunologic Leukocytosis. A case is described of a 23-year-old man with paranoid schizophrenia who had previously developed clozapine-induced leukopenia, and who presented with olanzapine-associated leukopenia and thrombocytopenia, in which treatment with lithium at 600mg/day, allowed olanzapine to be restarted without recurrence of hematologic abnormalities [115 ]. 

Grover S, Hegde A, Agarwal M, Sachdeva MS. Olanzapine-associated leukopenia and thrombocytopenia managed with liihium in a patient who developed leukopenia with clozapine in the past a case report. Prim Care Companion CNS Disord 2012 14(6). pii PCC.12101367. 

Akpitiar A, Salis O. Evaluation of the incidence of leukopenia and agranulocytosis in patients receiving combined clozapine and other anti-psychotics. BCP 2012 22(4) 313-9. 

---