Psychosomatics 48:530-531, November-December 2007
doi: 10.1176/appi.psy.48.6.530
© 2007 Academy of Psychosomatic Medicine
Quetiapine-Induced Leucopenia and Thrombocytopenia
B. Ravi Shankar, D.P.M., D.N.B. (Psych)
Received December 15, 2006; revised December 21, 2006; accepted January 7, 2007. From the Krishna Nursing Home, Tamil Nadu, India. Send correspondence and reprint requests to Dr. Shankar, 6AB, Swaranambika Lay Out, Coimbatore 641009, Tamil Nadu, India. e-mail: drravishankarbalu{at}gmail.com
© 2007 The Academy of Psychosomatic Medicine
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ABSTRACT
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Antipsychotic drugs can cause neutropenia, which can progress to life-threatening agranulocytosis if drug therapy is not interrupted. The newer atypical antipsychotics are reputedly without adverse hematological effects. Quetiapine is a recently introduced atypical antipsychotic. It is a dibenzothiazepine derivative and shows similarities with clozapine in that it is characterized by high 5-HT2-relative-to-DA2 receptor affinity. Although adverse effects are usually mild, the author reports here a case of leucocytopenia and thrombocytopenia with quetiapine treatment that required its discontinuation.
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INTRODUCTION
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Antipsychotic drugs can cause neutropenia, which can progress to life-threatening agranulocytosis if drug therapy is not interrupted. The newer atypical antipsychotics are putatively devoid of adverse hematological effects. Quetiapine is a recently introduced atypical antipsychotic. It is a dibenzothiazepine derivative; it shows similarities with clozapine and is characterized by high 5-HT2-relative-to-DA2 receptor affinity and virtually no affinity for muscarinic receptors. Although adverse effects are usually mild, more serious adverse effects, including leucopenia, have been reported infrequently. We report a case of leucocytopenia and thrombocytopenia with quetiapine treatment that required its discontinuation.
Case Report
"Mr. M" is a 45-year-old man with chronic mania. He is dysarthric as a result of lithium neurotoxicity that occurred many years ago. He was brought to the hospital by the police because of socially disruptive behavior, and he was admitted to our medium-security unit. He was agitated and assaultive. He had elevated mood, expansive ideas, and delusions of grandeur and persecution. In the past, he had been treated with various antipsychotics and mood stabilizers; however he had not been on any medications for 2 months before this admission. He was started on sodium valproate 1,500 mg, lorazepam 2 mg bid, and quetiapine 25 mg bid. The dose of quetiapine was gradually increased to 600 mg per day. For extreme agitation, he was also given IM zuclopenthixol acetate. Considering long-term management, 6 days after admission, he was started on zuclopenthixol depot 150 mg every 2 weeks. The lorazepam was tapered and stopped.
Several weeks before the current admission, his white blood-cell (WBC) count was 4.9 x 109/L (reference range: 4.5 x 109/L to 13.0 x 109/L); his neutrophil count was 2.8 x 109/L (reference range: 1.8 x 109/L to 8.0 x 109/L), and other cell counts were within normal ranges. Five weeks after this admission, his WBC and neutrophil counts fell, respectively, to 2.9 x 109/L and 1.4 x 109/L, and his platelet count was 140 x 109/L. The cell counts recovered on the 6th week, however, but fell again on the 7th week. The white-cell and neutrophil counts were 2,700 and 1,100 cells/mm3, respectively, and platelets were 146 x 109/L; the cell counts continued to hover around this level for the next few weeks.
Mr. M’s clinical history, physical examination, and laboratory tests did not show any other relevant medical disorder. He has had zuclopenthixol and valproate in the past without any adverse affect, and quetiapine was the newcomer to his treatment regimen. Therefore, we stopped quetiapine at Week 10. His WBC, neutrophil, and platelet counts continued to hover below normal. Two weeks after quetiapine was stopped, Mr. M again became hypomanic, and he was started on risperidone, which was increased to 5 mg per day. Six weeks after stopping quetiapine, his cell counts reached normal, and, by the 7th week, his WBC was 4.8 x 109/L; the neutrophil count was 3.1 x 109/L, and platelet count was 146 x 109/L. On Week 10, his WBC was 4.7 x 109/L, neutrophils were 2.6 x 109/L, and the platelet count was 152 x 109/L.
Both Mr. M’s antipsychotic medication and his valproate can cause leucopenia, and valproate, by itself, has a high propensity for causing thrombocytopenia. However, in this patient, there is clearly a chronological and causal relationship between quetiapine therapy and the development of leucopoenia and thrombocytopenia, and, after the cessation of quetiapine, there was a rapid return of the patient’s blood count to normal levels. The patient had no history of neuroleptic-induced granulocytopenia or hematological disorder. He did not develop any symptoms of infection, and no special treatment was needed.
A PubMed search yielded very few case reports of quetiapine-induced leucopenia and only one case report of pancytopenia. Leucocytopenia and agranulocytosis can be seen during treatment with all known conventional antipsychotics, with the risk of agranulocytosis estimated at 0.01% to 0.14%.1,2 The risk of leucocytopenia and agranulocytosis with clozapine is approximately 1% to 3% during the first 18 months of treatment, after which the risk is reduced to a level near that of conventional antipsychotics.3,4 Because quetiapine and clozapine are related in chemical structure and pharmacological profile,5,6 the same mechanism of bone marrow depression could be hypothesized.
Although there are no guidelines on monitoring blood counts during administration of quetiapine, this report underlines the importance of checking blood counts. We think that clinicians worldwide should also be aware of this hazardous side effect, and leukocyte counts should be considered. Unexpected and/or frequent, serious, or fatal side effects of new drugs must be watched closely, and, when observed, they must be reported to the authorities and noted in the scientific journals. Moreover, future research needs to address the incidence and risk factors for this rare but potentially fatal side effect.
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REFERENCES
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- Simpson GM, Edmond HP, Scarnak JJ: Neuroleptics and antipsychotics, in Meyler’s Side Effects of Drugs, 13th Edition. Edited by Dukes MNG. Amsterdam, The Netherlands, Elsevier BV, 1996, pp 117-135
- Lamarque V: Clozapine-associated agranulocytosis: a review of international experience. Encephale 1996; 22:35–36[Medline]
- Lieberman JA, Safferman AZ: Clinical profile of clozapine: adverse reactions and agranulocytosis. Psychiatr Q 1992; 62:51–70
- Atkin K, Kendall F, Gould D, et al: Neutropenia and agranulocytosis in patients receiving clozapine in the UK and Ireland. Br J Psychiatry 1996; 169:483-488
- Zeneca Pharma Ltd: Seroquel® (quetiapine). Product monograph, 1998, pp 1-25
- Goldstein JM: Preclinical pharmacology of new atypical antipsychotics in late-stage development. Exp Opin Invest Drugs 1995; 4:291–298
This article has been cited by other articles:
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A. Rahman, L. M Mican, C. Fischer, and A. H Campbell
Evaluating the Incidence of Leukopenia and Neutropenia with Valproate, Quetiapine, or the Combination in Children and Adolescents
Ann. Pharmacother.,
May 1, 2009;
43(5):
822 - 830.
[Abstract]
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ABSTRACT
INTRODUCTION
