Abstract
Antipsychotics are known to be associated with a risk of neutropenia [1], the best known association being with clozapine. Newer atypical antipsychotics have been developed with the view of being safer alternatives to clozapine. We present the case of a clozapine-naive patient who developed reversible leucopenia (white blood cell (WBC) count <4 × 109/L) and neutropenia (neutrophil count <1.5 × 109/L) in response to three different atypical antipsychotic medications.
The patient, a Caucasian woman, was first diagnosed with schizophrenia at the age of 50 in 2002. On initial presentation she exhibited bizarre delusions and poor self-care. Exacerbations of psychotic symptoms have led to five further hospital admissions.
Since being first diagnosed, the patient had been managed with quetiapine 600 mg. In a 2005 admission for worsening psychotic symptoms, baseline WBC and neutrophil counts were 4.4 × 109/L and 3.1 × 109/L respectively. Quetiapine was increased to 800 mg, and 10 days later she became leucopenic and neutropenic with a WBC count of 2.7 × 109/L and neutrophil count of 1.1 × 109/L. The quetiapine was subsequently ceased and 2 days later the WBC and neutrophil counts increased to 3.5 × 109/L and 1.8 × 109/L respectively. A trial of aripiprazole 15 mg was immediately prescribed, but 5 days later led to a decline of WBC to 2.9 × 109/L and of neutrophils to 0.9 × 109/L. The medication was continued and bloods were monitored for the next 4 days, however the neutrophil counts remained low (1.2 × 109/L, 1 × 109/L, and 1.3 × 109/L) and the aripiprazole was ceased. Four days later WBC and neutrophil counts normalized at 4 × 109/L and 1.6 × 109/L respectively.
As it had been the only effective and tolerable antipsychotic for the patient, it was decided to recommence quetiapine at a dose of 800 mg with regular blood monitoring. The plan was to cease quetiapine if neutrophils fell below a threshold of 1 × 109/L. Throughout the year neutrophil counts varied between 1.1 × 109/L and 3.6 × 109/L, and quetiapine was continued.
In 2008, the patient was again hospitalized because of worsening psychotic symptoms. On admission her WBC and neutrophil counts were 4.2 × 109/L and 2.5 × 109/L respectively, and a trial of olanzapine 10 mg was commenced. Two days later her WBC count fell to 3.8 × 109/L and neutrophil count fell to 0.5 × 109/L. The olanzapine was ceased and 4 days later the WBC and neutrophil counts normalized at 8.5 × 109/L and 5.4 × 109/L respectively.
In this case no other potentially haematotoxic drugs were taken concurrently, and the patient's blood counts were normal before initiating each different antipsychotic. No other cause of neutropenia was identified. Amisulpride, risperidone, pericyazine, and zuclopenthixol were antipsychotics that were trialled and did not cause neutropenia, however all were ceased due to extrapyramidal side effects.
The mechanism for drug-induced neutropenia has been studied extensively in regard to clozapine. The exact mechanism is unknown but is thought to have a large genetic component involving clozapine metabolites targeting predominantly peripheral blood neutrophils [1]. Olanzapine [2] and quetiapine [3] have previously been reported to cause neutropenia. It may be hypothesized that neutropenia seen in these drugs is due to a shared mechanism with clozapine, given their structural similarities. Aripiprazole, however, has a different chemical structure from clozapine, thus indicating that other factors may be contributing to the neutropenic effect. There is currently only one other report of aripiprazole induced neutropenia [4].
This case provides evidence as to the risk of leucopenia and neutropenia due to atypical antipsychotics other than clozapine. It also adds to a number of reported patients who have become neutropenic due to multiple atypical antipsychotics [4,5], suggesting a possible underlying genetic predisposition. On the basis of our case report it may be important to consider regular blood monitoring with the initiation of any atypical antipsychotic in any patient with a history of antipsychotic induced neutropenia.