Clozapine Response in Schizophrenia and Hematological Changes

Abstract

Background: Clozapine is the only effective medication for treatment-resistant schizophrenia; however, its mechanism of action remains unclear. The present study explored whether its effectiveness is related to changes in hematological measures after clozapine initiation.

Methods: Patients with treatment-resistant schizophrenia commenced on clozapine between January 2007 and December 2014 by the United Kingdom's largest mental health trust were identified from electronic patient records. Hematological data from these patients were obtained from a monitoring registry. White blood cell, neutrophil, and platelet count were assessed at baseline and during the early phase of clozapine treatment. Clozapine response at 3 months was defined as "much," or "very much" improved on the seven-point Clinical Global Impression-Improvement (CGI-I) subscale.

Results: In the total sample (n = 188), clozapine initiation was associated with a significant transient increase (peaking in weeks 3 to 4) in white blood cell, neutrophil, and platelet count (P < 0.001). There were 112 (59.6%) patients that responded to treatment; however, none of the hematological factors assessed at baseline, nor changes in these factors, were directly associated with treatment response.

Implications: Clozapine treatment is associated with transient hematological changes during the first month of treatment; however, there was no evidence that these were related to the therapeutic response.

FIGURE 1

Temporal profile of WBC, neutrophil (left y axis), and platelet (right y axis) counts for all patients initiated on clozapine displayed as change from baseline. Error bars represent ± 1 standard error.

FIGURE 2

Temporal profile of WBC (top panel), neutrophil (middle panel), and platelet (lower panel) counts by treatment response as change from baseline. Error bars represent ± 1 standard error.