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ADVERSE DRUG REACTIONS

Evaluating the Incidence of Leukopenia and Neutropenia with Valproate, Quetiapine, or the Combination in Children and Adolescents

Child & Adolescent Psychiatrist, Dallas Metrocare Services, Dallas, TX

Lisa M Mican, PharmD

Assistant Pharmacy Director, Austin State Hospital; Clinical Assistant Professor, College of Pharmacy, The University of Texas at Austin

Charles Fischer, MD

Senior Child and Adolescent Psychiatrist, Austin State Hospital

Angela H Campbell, PharmD MS

Clinical Pharmacist, Austin State Hospital; Clinical Assistant Professor, College of Pharmacy, The University of Texas at Austin

Reprints: Dr. Mican, Austin State Hospital, Pharmacy Department, 4110 Guadalupe St., Austin, TX 78751, fax 512/419-2788, lisa.mican{at}dshs.state.tx.us

BACKGROUND: At the Austin State Hospital, Austin, TX, a number of cases of neutropenia and leukopenia have been observed in children and adolescents who were treated with the combination of valproate and quetiapine. Use of this combination has raised concerns regarding an increased risk of hematologic toxicity.

OBJECTIVE: To evaluate the incidence of leukopenia and neutropenia associated with the use of valproate, quetiapine, or the combination in the child and adolescent population.

METHODS: This study was a retrospective evaluation of patients from the child and adolescent psychiatric service of the Austin State Hospital who were treated with valproate, quetiapine, or the combination. Subjects were selected from patients discharged between August 1, 2004, and August 31, 2007. Laboratory data were evaluated to determine the incidence and severity of leukopenia and neutropenia associated with valproate, quetiapine, and a combination of the 2.

RESULTS: A total of 131 patients were included in the study. Analysis of the laboratory data revealed a combined incidence of neutropenia and/or leukopenia of 44%, 26%, and 6% in the combination group, valproate monotherapy group, and quetiapine monotherapy group, respectively. Differences in the incidence of neutropenia and/or leukopenia between the quetiapine monotherapy group and valproate monotherapy group, as well as the quetiapine monotherapy group and the combination group reached statistical significance. A significant difference was found among groups based on absolute neutrophil count Common Toxicity Criteria severity (p < 0.001). The combination group differed significantly in incidence of moderate-to-severe neutropenia (14 cases) from both the valproate (5 cases) and quetiapine (0 cases) monotherapy groups. A significantly greater number (44%) of African American patients experienced neutropenia and/or leukopenia than white (not Hispanic or Latino; 29%) or Hispanic or Latino (11%) patients.

CONCLUSIONS: Patients treated with valproate or the combination of valproate and quetiapine should be monitored for the occurrence of leukopenia and neutropenia. Controlled studies are warranted to examine possible pharmacokinetic and pharmacodynamic interactions with the combination of valproate and quetiapine to further evaluate the hematologic findings of this study.

Key Words: adolescents, children, divalproex, granulocytopenia, leukopenia, neutropenia, quetiapine, valproate, valproic acid

Published Online, April 28, 2009. www.theannals.com, DOI 10.1345/aph.1L617