John Piletz, Debra Hoppensteadt, Walter Jeske, Jawed Fareed, James Sinacore, Brittany Garlenski and Angelos Halaris
Objectives: Test the prevailing hypothesis that depressive illness is associated with platelet hyperactivity and that treatment with an atypical antipsychotic with established antidepressant efficacy - quetiapine - will normalize platelet activity.
Methods: Forty-seven outpatients with major depressive disorder (MDD) and 27 healthy controls (HC) without evidence of cardiovascular disease were enrolled. Behavioral rating scales and medical tests preceded baseline assessments of (1) platelet-rich plasma (PRP) aggregometry and (2) whole blood flow cytometry (P-selectin surface labeling). The measures were repeated in those MDD subjects who completed 8 weeks (n=27) or 12 weeks (n=19) of treatment with quetiapine.
Results: Untreated MDD compared to HC subjects displayed more platelet aggregation when PRP was stirred agonist-free (p=0.021). Other platelet measurements at baseline such as in vitro agonist-stimulated PRP aggregometry or P-selectin expression by flow cytometry did not distinguish MDD from HC subjects. After 8 weeks on quetiapine, a reduced (now normal) agonist-free aggregatory response to stirring (p=0.035) was observed. By 12 weeks the aggregometry response to arachidonic acid (AA) was also lowered (p=0.016 vs. pretreatment; p=0.001 vs. HC). Other agonist additions (ADP, epinephrine, or collagen) failed to distinguish MDD from HC. There were no significant associations between mood rating scores and any form of platelet activity at any time point on quetiapine.
Limitations: High percentage of dropouts attributable to dose-related side effects limited the post-treatment assessments.
Conclusions: The hypothesis that untreated depression is associated with more active platelets, was confirmed, but this finding was confined to the “resting”, or agonist-free state. Quetiapine treatment normalized this resting activity and led to a lower-than-normal response to AA-induced aggregation after 12 weeks of treatment. These findings confirm that 8 weeks treatment with quetiapine can normalize at least one form of platelet hyperactivity, but the lower-thanhealthy response to AA after 12 weeks on quetiapine warrants further study.