Orthostasis and platelet aggregation before and after nefazodone

The effect of nefazodone (N) on platelet aggregability (PA) to an epinephrine (E) agonist, plasma (E) and plasma norepinephrine (NE) to an orthostatic challenge was examined in 8 healthy volunteers. Subjects were examined before and after 200 mg BID of N for 8 days. Six of 8 subjects completed the protocol. Three were orthostatic (diastolic blood pressure drop >5 mm Hg or pulse increase >20 beats per minute) after standing 5 minutes and 3 were not. For the entire group (n=6), N did not change mean NE (pg/ml), E (pg/ml), or PA (%) but subjects orthostatic (ortho) upon standing had increased mean NE, E, and PA while those subjects not orthostatic (n=3) had decreased NE, E, and PA. NE E PA before after before after before after All n=6 389 496 247 318 33.5 32.1 Ortho 267 660 92 466 29.7 46.7 Not-ortho 512 332 402 170 37.3 17.7 The a blocking properties of N may have caused vasodilation, increased NE and E, with resultant increase in PA in the orthostatic subjects. In the non-orthostatic subjects platelet 5HT₂ blockade by N and/or decreased E could explain the decreased PA. Additional studies are clearly needed to further define the hemodynamic effects of N.