Clozapine treatment following blood dyscrasia

Dunk et al (2006) investigated 53 patients who were rechallenged with clozapine following leucopenia or neutropenia during previous therapy and found that 33 did not experience a second episode of blood dyscrasia and were able to continue drug treatment. This result is of considerable clinical relevance because it suggests that some patients with leucopenia or neutropenia may unnecessarily be denied effective clozapine treatment.

We agree that there may be two types of clozapine-associated neutropenia: an early sign of incipient agranulocytosis and a more common transient and harmless phenomenon, not necessitating the discontinuation of drug treatment. Transient neutropenia (defined as a return of the neutrophil count to normal values without changing the clozapine dosage) was found in 22% of 68 patients treated with clozapine for the first time (Hummer et al, 1994). 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 (morning pseudoneutropenia) have also been described in several clozapine-treated patients (Ahokas & Elonen, 1999; Esposito et al, 2004).

The actual issue might therefore not be which patients could be rechallenged with clozapine following drug-associated neutropenia but which could be maintained on clozapine despite this side-effect. Laboratory screening tests, including the use of a hydrocortisone test, are being devised to determine whether clozapine-associated neutropenia is transient or malignant (Murry & Laurent, 2001). Until these tests become available for routine use, it is necessary to increase the frequency with which white blood cell counts are determined. As first suggested by Ahokas & Elonen (1999), when the absolute neutrophil count is below the normal range in the morning, the test should be repeated in the afternoon of the same day before a decision to stop clozapine treatment is made. This might be the basis for further clarification of the significance of transient neutropenia.