Letters to the Editor
Clozapine-Induced Aplastic Anemia in a Patient With Parkinson’s Disease
Dear Editor:
Psychosis is a common complication of the drug treatment of Parkinson’s disease (occurring in approximately 25% of patients) and therefore constitutes a serious public health problem. All patients suffering from idiopathic Parkinson’s disease, and especially elderly patients with dementia, are at risk of developing delusions or hallucinations. The most prominent psychotogenic factors are dopaminomimetic agents, which may induce dopamine hypersensitivity in the frontal and limbic dopamine projection regions and consequently, either directly or indirectly, elicit psychotic signs and symptoms (1). A Parkinson’s disease–related cholinergic deficit combined with an age-related further loss of cholinergic integrity also plays a prominent role (1). Treating this complication is difficult: because of their selective dopamine receptor antagonistic effects, most typical antipsychotic drugs worsen motor symptoms of Parkinson’s disease. As a consequence of a nonselective antagonism at both serotonergic and dopaminergic receptors, atypical antipsychotics such as clozapine or olanzapine are associated with fewer extrapyramidal side effects (2). Clozapine was the first atypical antipsychotic drug to be introduced into clinical use in several European countries, in the late 1960s (3). Clozapine treatment is associated with wide side effects that include the following: blood-cell dyscrasias, benign granulocytopenia, transient granulo- cytosis, and a risk of agranulocytosis as high as 0.5% to 1% (4); transient fever in up to 50% of the patients; sedation; and considerable body-weight gain. The mechanisms underlying these side effects are still unknown, but recent data suggest that the metabolism of clozapine and its immunomodulatory effects may play a role. Aplastic anemia in all its features emerging during clozapine therapy has not been documented in the literature. We present a case of clozapine-induced aplastic anemia.
Case Report
A 53-year-old man with Parkinson’s disease (according to ICD-10 criteria) developed a dopamine-induced psychosis with hallucinations. Because of his persisting psychotic symptoms, he was admitted to a psychiatric hospital, and antipsychotic pharmacotherapy of 50 mg clozapine daily was started. He developed fever after 1 week, and his blood tests revealed abnormalities (neutrophil count < 500/L, platelet count 93 000/L, and reticulocyte count < 20 000/L). Clozapine therapy was discontinued and he was admitted to our clinic. According to the criteria of the International Aplastic Anemia Study Group, we diagnosed a severe form of drug-induced aplastic anemia (neutrophil count < 500/L, platelet count 89 000/L, and reticulocyte count < 20 000/L). He received blood transfusions, and we started therapy with hematopoietic growth factors (r-metHuG-CSF) (5) and antibiotics. The Parkinson’s disease was treated with dopamine and apomorphine. After 14 days, he was responding to the therapy, and the aplastic anemia disappeared. The psychosis with delusions and hallucinations was still evident, and we established a neuroleptic therapy with quetiapine. The therapy with hematopoietic growth factors was discontinued.
We hypothesize that clozapine induced the severe aplastic anemia. The major classes of myelotoxic drugs are known, but the mechanisms by which certain agents cause aplastic anemia are still unclear. We suggest cautious use of clozapine in patients with Parkison’s disease.
References
1. Wolters EC, Berendse HW. Management of psychosis in Parkinson’s disease. Curr Opin Neurol 2001;14:499–504.
2. Van De Vijver DA, Ross RA, Jansen PA, Porsius AJ, De Boer A. Antipsychotics and Parkinson’s disease: association with disease and drug choice during the first 5 years of antiparkinsonian drug treatment. Eur J Clin Pharmacol 2002;58:15761.
3. Angst J, Bente D, Berner P, Heimann H, Helmchen H, Hippius H. Das klinische Wirkungsbild von Clozapin (Untersuchungen mit dem AMP-System). Pharmacopsychiatrie 1971;13:201–11.
4. Alvir JMJ, Liebermann JA, Saffermann AZ, Schwimmer JL, Schaaf JA. Clozapine-induced agranulocytosis. N Engl J Med 1993;329:162–7.
5. Vial T, Gallant C, Choquet-Kastlevsky G, Descotes J. Treatment of drug induced agranulocytosis with hematopoietic growth factors. A review of the clinical experience. Biodrugs 1999;11:185–200.
Marc Ziegenbein, MD; Anja Steinbrecher, MD;
Petra Garlipp, MD
Hannover, Germany
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