Treatment of clozapine-induced granulocytopenia with lithium (two observations)

Despite the availability of new treatments, the antipsychotic effectiveness of clozapine has not been matched yet Unfortunately, its regulation is limitated by the side effects. The most detrimental is the hematologic toxicity (neutropenia and agranulocytosis) which requires a regular biological monitoring. Treatment with clozapine must be stopped in those cases of secondary granulocytopenia for about 3 % of the patients. The current psychiatric drug lithium carbonate has an opposite effect: it can induce leukocytosis. Thus, lithium carbonate is administered in leukopenia, as well as in many hematologic and imunological diseases. However, few teams have used lithium in order to alleviate clozapine-induced granulocytopenia. We report here 2 patients who developed severe neutropenia (neutrophil count < 1.5 x 10 (9)/L) and for whom the use of lithium enabled us to continue the treatment by clozapine. The first patient had a granulocyte rate constitutionaly low which rapidly decreased with clozapine. Thanks to the administration of lithium, he recovered quickly a normal blood cell count, which in fact was much higher than his normal rate. According to our research, it's the first time that lithium is reported to be so efficacious in a patient with such a low rate of granulocytes before treatment. It maybe that clozapine is not used for those kinds of patients. The second patient developed granulocytopenia after one year of treatment with clozapine. The use of lithium increased so much the number of granulocytes that we continued the treatment with clozapine alone. After 4 months, there is no reappearance of granulocytopenia. We must take into account the partial and contradictory reports in the literature. However, if this result is confirmed, it could be of a high interest to extend the prescription of clozapine, the most effective current antipsychotic drug.