Blood Dyscrasias Induced by Psychotropic Drugs

Abstract

Drugs can cause a variety of blood dyscrasias, e. g., by interfering with hematopoiesis in the bone marrow or damaging mature blood cells by antibodies. Although numerous reports on the risks of adverse hematological effects associated with psychotropic drugs have led to stringent monitoring requirements for some compounds, particularly neuroleptics, it is still difficult to estimate the true prevalence of such risks. Sixteen episodes of thrombocytopenia, 63 of neutropenia, 22 of agranulocytosis, 4 episodes of severe neutro- and thrombocytopenia, and 2 of pancytopenia were documented by the drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) in a population of 122,562 patients between 1993 and 2000. All cases were related to the epidemiological data provided for this population and systematically analyzed as regards history of medication, co-medication, and the clinical course. Putative risk rates for the main groups of medications and a number of drugs could be estimated with this database. Most changes in the white blood cell counts, which were rated as probably or definitely drug-induced, were attributed to clozapine (0.18 % of patients exposed), carbamazepine (0.14 %) and perazine (0.09 %). In patients on newer atypical neuroleptics, we documented neutropenia assumed to be probably or definitely drug-related in five patients during treatment with olanzapine and in one case with risperidone. In all five olanzapine-related cases, the drugs were the sole cause of the adverse drug reactions. All surveyed patients who received clozapine showed no difference in age and gender distribution from those who developed hematological changes. Incidences of hematological changes for antidepressants were much lower (about 0.01 %). Although the methodological accuracy of these findings has to be critically discussed these data could be of considerable clinical relevance and should be helpful in making clinical treatment decisions.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…Carbamazepine may be a risk factor for leucopenia,828, 829, 830 although this finding is not robust 831. This side effect is generally reversible with dose reduction or discontinuation.…”

“…Clozapine carries the greatest risk for drug‐induced changes in white blood cell counts, with approximately 0.18% of patients experiencing changes rated as probably or definitely drug induced 828. All patients started on clozapine should have a baseline haematological profile established and be enrolled in the clozapine monitoring programme which requires regular monitoring of haematological parameters: weekly at first and then every 2‐4 weeks later in the course of treatment 833…”

Pediatric Olanzapine Intoxications and Plasma Exchange Application in One Case: Four Case Reports

“…Atipik antipsikotik ilaçlarda agranülositoz bilinen bir yan etkidir ve en sık klozapin ile görülür (8). Olanzapin kullanan hastalarda doz bağım-lı olarak lökopeni gelişebildiği bildirilmektedir (9).…”

Is prolonged stem cell mobilization detrimental for hematopoiesis?

“…Phenothiazines were one of the first drugs that were documented to cause bone marrow hypoplasia or suppression. The effects of phenothiazines range from minor anaemia, to life-threatening granulocytopenia, thrombocytopenia, agranulocytosis, and trilineage bone marrow aplasia [2,4,5]. The mechanism of phenothiazine-induced bone marrow suppression is unknown.…”

“…In several cases immune-mediated mechanisms, which include drug-dependent anti-blood cell antibodies, resulting in peripheral cell destruction, had been suggested. The suppression of hematopoetic precursors by prolonged administration of the drug without an immune component was also proposed [2,4]. In general, it is likely that multiple mechanisms may contribute to the etiology of drug-induced blood dyscrasias [5].…”