Letters to the Editor
Quetiapine-Induced Leucopenia: Possible Dosage-Related Phenomenon
Dear Editor:
Quetiapine is as effective as haloperidol and chlorpromazine in relieving both the positive and negative symptoms of schizophrenia at dosages ranging from 150 to 750 mg daily (1–3).
In premarketing placebo-controlled trials, quetiapine use has been associated with a dosage-related decrease in total and free thyroxin (T4), with transient leukopenia, and with an elevation from baseline in cholesterol, triglyceride, and hepatic transaminases (4).
Case Report
MM is a 41-year-old woman diagnosed with schizophrenia at age 22 years. While taking chlorpromazine 600 mg daily, she was well (that is, her schizophrenia was episodic, with no interepisode residual symptoms) and functioned independently in the community for over 18 years.
Nonadherence to treatment preceded the recurrence of positive symptoms, social withdrawal, and poor personal hygiene, which led to her readmission to a psychiatric hospital for over 7 months in 2001. Pharmacotherapy with optimal dosages of olanzapine and risperidone did not appreciably improve her target symptoms. After haloperidol 10 mg daily was commenced, improvement in the target symptoms was evident, and she was discharged home. She was readmitted 7 weeks later because she had not adhered to follow-up plans and had discontinued her medication without medical advice. After she developed extrapyramidal side effects (EPSEs), haloperidol was replaced by quetiapine at 150 mg daily, titrated to 600 mg daily over 4 weeks, and the EPSEs resolved. Her pre-quetiapine white blood cell count (WBC) was 6.6, and her absolute neutrophil count was 4.0. Four weeks later, a repeat complete blood count revealed leukopenia of 1.7 and absolute neutropenia of 0.3. The following day, the leukocyte and absolute neutrophils counts were 2.0 and 0.2, respectively. MM agreed to the substitution of chlorpromazine for quetiapine. She had no clinical evidence of infection, her vital signs were normal, and she had no known prior or contemporanious medical history that might explain the laboratory findings. At quetiapine 450 mg daily, 300 mg daily, 150 mg daily, and 1 week after discontinuation, the respective WBC and absolute neutrophil counts were 2.4 and 0.4, 4.8 and 2.8, 6.2 and 4.6, 6.4 and 4.7 (within normal limits). MM refused a rechallenge with quetiapine.
This patient experienced a quetiapine-associated, dosage-related, reversible leucopenia. Hematological abnormalities have been reported with the use of atypical antipsychotic (AP) drugs, especially clozapine-induced agranulocytosis (5). The mechanism by which these drugs induce these abnormalities remains uncertain, but they could be immunologically mediated or caused by direct bone-marrow toxicity (6). Unlike clozapine, other atypical APs do not require adherence to a rigorous laboratory monitoring protocol. We consider it essential that physicians inform patients about the potential hematological abnormalities and educate patients about the signs and symptoms of reduced blood cell counts. Prudent clinical management also warrants routine WBC monitoring, at least during initiation of quetiapine and, possibly, other atypical APs. The possible absence of physical symptoms to alert both clinician and patient to immunological compromise jeopardizes timely identification of potentially marked neutropenia. We also think an efficient and effective strategy is needed to identify hematologically compromised patients who are at high risk of developing medical complications associated with neutropenia, before they receive atypical antipsychotics.
References
1. Arvanitis LA, Miller BG. Multiple fixed doses of “seroquel” (quetiapine) inpatients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. Biol Psychiatry 1997;42:233–46.
2. Small JG, Hirsch SR, Arvanitis LA, Miller BG, Link CGG, the Seroquel Study Group. Quetiapine inpatients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Arch Gen Psychiatry 1997;54:549–57.
3. Peuskens J, Link CG. A comparison of quetiapine and chlorpromazine in the treatment of schizophrenia. Acta Psychiatr Scand 1997;96:265–73.
4. AstraZeneca. Seroquel Product Monograph 2001. Compendium of pharmaceuticals and specialities (CPS). 36th ed. Ottawa: Canadian Pharmacists Association; 2001. p 1424.
5. Anderman B, Griffith RW. Clozapine-induced agranulocytosis: a situation report up to August 1976. Eur J Clin Pharmacol 1977;11:199–201.
6. Krupp P, Barnes P. Clozapine-associated agranulocytosis: risk and aetiology. Br J Psychiatry 1992;160 (Suppl 17):38–40.
Oloruntoba Oluboka, MBBS, FRCPC
David Haslam, MD, MSc, FRCPC
Treena Lam, MD, CCFP
Diane Bown-Demarco, RN
North Bay, Ontario
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