The effect of atypical antipsychotics on platelet aggregation

Abstract

Background: There is a high prevalence of arterial thrombosis in schizophrenia. Several studies investigated the cause of this high risk among schizophrenic patients and variable finding reported. The aim of this study was to investigate whether second generation antipsychotics (risperidone, olanzapine and ziprasidone) exert antiplatelet action in the presence of different platelet agonists. Methods: We performed an in vitro study of different antipsychotics (risperidone, olanzapine and ziprasidone) effect on platelet aggregation induced by different platelet agonists (ADP, collagen, serotonin and epinephrine) when added to blood of healthy volunteers using Multiplate® analyzer. Results: Risperidone and ziprasidone but not olanzapine showed clinically significant inhibition of platelet aggregation induced by by serotonin, while only ziprasidone showed statistically significant inhibition on serotonin aggregation. All tested antipsychotics showed clinically (but not statistically) significant inhibition on platelet aggregation induced by epinephrine. On the other hand, no remarkable effect of antipsychotics on platelet aggregation induced by ADP or collagen was observed. Marked amplification reaction between serotonin and epinephrine was observed (AUC 66 U). When antipsychotics were added to serotonin-epinephrine combination, all of them produced AUC inhibition in a dose-dependent manner with highest potency for risperidone (IC50= 14.86 nM) and the lowest potency for olanzapine (IC50= 27.56 nM). Conclusion: All tested antipsychotics showed clinically (but not statistically) significant inhibition effect on platelet aggregation induced by either serotonin or epinephrine. All antipsychotics studied inhibited platelet aggregation induced by a combination of serotonin and epinephrine in a dose-dependent manner.