Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via HighWire Citing Articles via Google Scholar Articles by Nair, P. Articles by Lippmann, S. Search for Related Content PubMed Citation Articles by Nair, P. Articles by Lippmann, S. Atypical Neuroleptics Schizophrenia Spectrum Disorders Anticonvulsants

Is Leukopenia Associated With Divalproex and/or Quetiapine?

TO THE EDITOR: Leukopenia is defined as a WBC count below 3,000/mm³.¹ It is sometimes caused by a variety of pharmaceuticals, including many mood stabilizer and antipsychotic drugs.² Older and newer generation antipsychotic medicines are included. Clozapine, carbamazepine, olanzapine, oxcarbazepine, quetiapine, risperidone, and valproate products are reported as potential causes of bone marrow suppression.

The vignette documents a case of declining WBC count in a patient given prescriptions for divalproex and quetiapine. The patient’s hemogram returned to normal after these medicines were discontinued.

Case Report

Ms. A, a 33-year-old African American woman with schizophrenia, became psychotic when she was noncompliant with her medicines, and she was then admitted to the hospital. One week before this, she had been taking divalproex, 500 mg/day, and quetiapine, 400 mg/day, while hospitalized with a WBC count of 6,200/mm³ (63.6% granulocytes).

On this admission, her WBC count was 6,300/mm³ with 49.4% granulocytes. Divalproex, 2 g/day, and quetiapine, 800 mg/day, were started. A repeat blood count revealed a WBC count of 3,600/mm³ and 30.6% granulocytes. Because of the decline in WBC count, both medications were discontinued.

Ms. A had no signs of infection or nutritional or immunological dysfunction. An abdominal ultrasound was normal. On the next day, her WBC count remained unchanged (3,600/mm³), but her granulocytes increased to 46.6%. Divalproex and/or quetiapine-induced bone marrow suppression was suspected.

Ms. A’s regimen was then changed to 30 mg/day of aripiprazole. Two days later, her WBC count increased to 3,700/mm³ with granulocytes at 37.4%. Aripiprazole was continued. After 3 more days, her hemogram returned to normal (a WBC count of 5,400/mm³ and 44.2% granulocytes). With mental status improvement, Ms. A was later discharged with no complications.

Discussion

Despite not meeting strict criteria for leukopenia, the decline in WBC count was a concern since doses of both medicines had just recently been increased. The patient’s hemogram returned to normal when divalproex and quetiapine were discontinued.

Leukopenia can result from a variety of mechanisms: decreased marrow production, increased peripheral destruction, or a combination of these.³ Drug-induced leukopenias can occur in a dose-dependent relationship or in an idiosyncratic, dose-independent hypersensitivity reaction.

Leukopenia has been reported in 0.4% of adults treated with divalproex.⁴ Thrombocytopenia is more common, although neutropenia has also been documented. These are usually reversible with dose reduction and/or medication discontinuation.

Leukopenia can also develop in approximately 1% of the subjects treated with quetiapine, and it resolves upon discontinuation.⁵ We are unaware of any cases of persistent neutropenia or agranulocytosis. Risk factors include pre-existing low WBC counts and a history of drug-induced blood dyscrasias. The aripiprazole package insert cites hematological adversities. We are unaware of such documentations in other medical literature.

Although this report does not substantiate an etiological relationship to these pharmaceuticals, no other causes were established. The WBC count dropped during treatment with divalproex and quetiapine and improved with drug discontinuation. Divalproex, quetiapine, or the combination could have caused the decline. Use over time should clarify the true risk potential. When prescribing these medicines, hematological assessment should be considered. If such a complication is suspected, immediate withdrawal of the medication is warranted.

REFERENCES

1. Goforth HW, Raval CR, Sharma G, Rao MS: Clozapine therapy: timing is everything. Current Psychiatry Online 2003; 2(8) (http://www.currentpsychiatry.com)
2. Atkin K, Kendall F, Gould D: The incidence of neutropenia and agranulocytosis with clozapine in the UK and Ireland. Br J Psychiatry 1996; 169: 483–488
3. Kimball JP: R.W. Johnson Pharmaceutical Research Institute: drug induced leukopenia. (http://www.bloodline.net)
4. Nasrallah HA, Kuo I: Side effect in the treatment of bipolar affective disorder. Psychiatry and Mental Health 2003; 8(2) (http://www.medscape.com)
5. Croarkin P, Rayner T: Acute neutropenia in a patient treated with quetiapine. Psychosomatics 2001; 42:368[Free Full Text]

This article has been cited by other articles:

				D. O. Yalcin, E. Goka, M C. Aydemir, and C. Kisa Is aripiprazole the only choice of treatment of the patients who developed anti-psychotic agents-induced leucopenia and neutropenia? A case report J Psychopharmacol, May 1, 2008; 22(3): 333 - 335. [Abstract] [PDF]

Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via HighWire Citing Articles via Google Scholar Articles by Nair, P. Articles by Lippmann, S. Search for Related Content PubMed Citation Articles by Nair, P. Articles by Lippmann, S. Atypical Neuroleptics Schizophrenia Spectrum Disorders Anticonvulsants

Get information about faster international access.

Privacy Policy

Copyright © 2005 Academy of Psychosomatic Medicine. All rights reserved.

Home | Search | Current Issue | Past Issues | Subscribe | All APPI Journals | Help | Contact Us