Comment on "lithium and clozapine rechallenge: a retrospective case analysis".

Sir: We refer to the interesting article from Drs. Kanaan and Kerwin 1 concerning the adjunctive use of lithium to treat clozapine-induced neutropenia. Immediate discontinuation of clozapine treatment has always been the first therapeutic step in cases of severe to moderate neutropenia and impending agranulocytosis. However, some physicians are reluctant to terminate or even to interrupt cloza-pine treatment in patients with neutropenia, as the drug is often a last resort for those with complex symptomatologies. The retrospective study by Drs. Kanaan and Kerwin suggests that lithium coadministration is an effective and safe strategy that may allow continuation of clozapine treatment despite the occurrence of neutropenia. This result is of considerable clinical relevance because it potentially provides an alternative to the interruption of clozapine treatment in severe cases in which other antipsychotic drugs are ineffective. However, some clozapine-associated neutropenia may be transient and harmless, and therefore may not require discon-tinuation of the drug treatment nor lithium adjunction. Transient neutropenia (defined as a return of the neutrophil count to normal values without changing the clozapine dosage) has been shown to occur in 22% of 68 patients treated with clozapine for the first time. 2 Neutropenia of short duration (2–5 days) and weekly benign variations of the neutrophil count have been reported. Marked circadian variations in the number of circulating neutrophils, i.e., morning pseudoneutropenia, have also been described in several clozapine-treated patients. It seems therefore essential, before interrupting clozapine treatment, to determine whether drug-induced neutropenia is transient or malignant. Laboratory screening tests, including the use of a hydrocortisone test, are being devised to make such a distinction. 5 Until these tests become available for routine use, it is necessary to increase the frequency with which neutrophil counts are determined. As first suggested by Ahokas and Elonen, 3 when the absolute neutrophil count is below the normal range in the morning, the test should be repeated the same day in the afternoon before a decision to stop clozapine treatment or to consider lithium coadministration is made. Dr. Esposito reports no financial affiliation or other relationship relevant to the subject matter of this letter. REFERENCES 1. Kanaan RA, Kerwin RW. Lithium and clozapine rechallenge: a retrospective case analysis. Two-year follow-up of a patient with successful continuation of clozapine treatment despite morning pseudoneutropenia [letter]. Is it possible to distinguish between benign and malignant neutropenia in clozapine-treated patients by means of a Sir: We are grateful to …