Hematological Side Effects of Atypical Antipsychotic Drugs

Abstract

Atypical antipsychotics cause less frequently extrapyramidal system symptoms, neuroleptic malignant syndrome and hyperprolactinemia than typical antipsychotics. However hematological side effects such as leukopenia and neutropenia could occur during treatment with atypical antipsychotics. These side effects could lead to life threatening situations and the mortality rate due to drug related agranulocytosis is about 5-10%. There are several hypothesis describing the mechanisms underlying drug induced leukopenia and/or neutropenia such as direct toxic effects of these drugs upon the bone marrow or myeloid precursors, immunologic destruction of the granulocytes or supression of the granulopoiesis. Clozapine is the antipsychotic agent which has been most commonly associated with agranulocytosis. A nitrenium ion which is formed by the bioactivation of clozapine is thought to have an important role in the pathophysiogy of this adverse effect. Aside from clozapine, there are several case reports reporting an association between olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole and leukopenia. We did not find any study or case report presenting amisulpride or sulpride related hematological side effects in our literature search. Patients who had hematological side effects during their previous antipsychotic drug treatments and who had lower baseline blood leukocyte counts, have higher risk to develop leukopenia or neutropenia during their current antipsychotic treatment. Once leukopenia and neutropenia develops, drugs thought to be responsible for this side effect should be discontinued or dosages should be lowered. In some cases iniatition of lithium or G-CSF (granulocyte colony-stimulating factor) therapy may be helpful in normalizing blood cell counts. Clinicans should avoid any combination of drugs known to cause hematological side effects. Besides during antipsychotic treatment, infection symptoms such as fever, cough, sore throat or fatigue should be evaluated closely and routinely. In this review, all up to date studies including case reports presenting or searching for atypical antipsychotic drugs related hematological side effects have been reviewed and possible mechanisms leading to these adverse effects and suggested treatment modalities have been discussed..

Keywords

• Atypical antipsychotics, hematological side effects, leukopenia

Atipik Antipsikotik İlaçların Hematolojik Yan Etkileri

Abstract

Atipik antipsikotikler ekstrapiramidal sistem yan etkilerine, nöroleptik malign sendroma ve hiperprolaktinemiye tipik antipsikotiklere göre daha az sıklıkla yol açmaktadır. Bununla birlikte atipik antipsikotiklerle lökopeni ve nötropeni gibi hematolojik yan etkiler ortaya çıkabilmektedir. Bunlar yaşamı tehdit edici durumlara yol açabilmektedir ve ilaçlara bağlı olarak gelişen agranülositozdan kaynaklanan ölüm oranı %5-10'dur. İlaçlara bağlı lökopeni ve/veya nötropeni gelişiminin altında kemik iliği ya da myeloid öncüllere doğrudan toksik etki, granülositlerin immunolojik yıkımı ya da granülopoezin baskılanması gibi çeşitli mekanizmalar yatmaktadır. Literatürde agranülositozla en çok ilişkilendirilen antipsikotik ilaç klozapindir ve ilacın biyoaktivasyonu ile oluşan bir nitrenyum iyonunun bu yan etki gelişiminde önemli bir role sahip olduğu düşünülmektedir. Klozapinden başka olanzapin, ketiyapin ve risperidonla ilişkili lökopeni olgu bildimleri de bulunmaktadır. Ziprasidon ve aripiprazol lökopeniye nadiren yol açmakta ve literatürde amisülprid ve sülpridle ilişkili hematolojik yan etkilere dair olgu bildirimi bulunmamaktadır. Önceki antipsikotik tedavileri sırasında hematolojik değişiklikler yaşayan ve tedavi başlangıcındaki beyaz küre sayıları normal sınırların altında olan hastalar lökopeni ve nötropeni gelişimine karşı yüksek risk altındadırlar. Lökopeni ve nötropeni ortaya çıktığında kullanılmakta olan ilaç kesilebilmekte ya da doz azaltılabilmektedir. Kimi zaman lityum ve G-CSF tedavileri kan hücrelerinin sayısını normale döndürmede faydalı olabilmektedir. Klinisyenler hematolojik yan etkilere yol açtığı bilinen ilaçları birlikte kullanmaktan kaçınmalı ve antipsikotik tedavisi sırasında vücut ısısında yükselme, öksürük, boğaz ağrısı ve yorgunluk gibi enfeksiyon belirtileri düzenli olarak kontrol edilmelidir. Bu gözden geçirme yazısında klozapin, olanzapin, ketiyapin, risperidon, aripiprazol ve ziprasidonla ilişkili hematolojik yan etkilerle ilgili olgu bildirimleri özetlenecek ve bu hematolojik yan etkilere yol açan olası mekanizmalar ve tedavi yaklaşımları tartışılacaktır.

Keywords

• Atipik antipsikotikler, hematolojik yan etki, lökopeni

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