Continuing clozapine treatment with lithium in patients with neutropenia or leukopenia

Clozapine (CLZ) is a second-line antipsychotic drug that is used for treatment-resistant schizophrenia. Despite its effectiveness, CLZ has some serious side effects. Agranulocytosis and neutropenia are life-threatening side effects of CLZ. There are an incidence of agranulocytosis of around 1% and neutropenia of about 3%, with the highest risk within the first 6–18 weeks of treatment. Lithium increases the neutrophil count and total White Blood Cell (WBC) as a side effect. The mechanism is not completely understood: direct stem cell stimulation and stimulation of granulocytemacrophage colony-stimulating factor have all been suggested. There isn’t a defined serum level for neutrophils but a minimum lithium serum level of 0.4 mmol/l may be required. We present a series of three hospitalized patients with schizophrenia. While they had demonstrated poor response to multiple antipsychotic trials, CLZ was started. Case 1, E.Y was 24-year-old female with a history of schizophrenia for 6 years and has had suicide attempts. Leukopenia occurred (WBC: 3.60 K/uL) 3 weeks after starting CLZ treatment (400 mg daily). CLZ treatment continued with lithium. The leukocyte counts became normal after administration of lithium (300 mg daily). Time without blood dyscrasia after lithium administration was 6 months. The patient had a normal WBC count of 4.630 K/uL in last examination. Case 2, A.A was a 50-year-old female diagnosed as schizophrenia for 25 years. Neutropenia (neutrophil: 1.450 K/uL, WBC: 2.950 K/uL) occurred 4 weeks after starting CLZ treatment. Treatment with CLZ (300 mg daily) continued with lower dosages of CLZ (100 mg daily) and lithium after hematology consultation. The neutrophil counts became normal after administration of lithium (600 mg daily). Lithium treatment continued at a dose of 300 mg daily. Time without blood dyscrasia after lithium administration was 30 months. During the 30 months of treatment, the patient’s WBC and neutrophil counts remained in the range of 4.170 K/uL to 8.340 K/uL for WBC and 1.90 K/uL to 4.250 K/uL for neutrophil. Case 3 A.I was 43-year-old female diagnosed as schizophrenia and Obsessive compulsive disorder for 27 years. 8 weeks after initiation of treatment with CLZ neutropenia (neutrophil: 0.950K/uL, WBC: 1.80K/uL) occurred. CLZ (400 mg daily) was discontinued after hematology consultation. Schizophrenia symptoms severely worsened after CLZ withdrawal. Symptom control after CLZ re-challenge with lithium(600 mg daily) was good. The neutrophil counts became normal after administration of lithium. Time without blood dyscrasia after CLZ re-challenge was 8 months. Lithium treatment continued at a dose of 300 mg daily. The patient had a normal WBC count of 6.650/uL and neutrophil count of 3.40 K/uL in last examination. In our own experience the patients responded well to CLZ treatment, in terms of clinical improvements in psychotic symptoms and reduction in suicide. Lithium may be useful in increasing the WBC in patients in those, who develop neutropenia or leukopenia while treated with CLZ as in our cases. If the WBC continues to fall despite lithium treatment, consideration should be given to discontinuing CLZ. Patients who are unresponsive to other antipsychotics and remain significantly distressed with poor quality of life and psychotic symptoms should be considered for CLZ usage in combination with lithium when neutropenia or leukopenia occurred.