Effect of single-dose sertraline on the hypothalamus-pituitary-adrenal system, autonomic nervous system, and platelet function.
OBJECTIVE
Pharmacological treatment with selective serotonin reuptake inhibitors (SSRIs) is thought to decrease coronary risk in patients with depressive disorder. Selective serotonin reuptake inhibitor intake may (1) attenuate the hypothalamus-pituitary-adrenal (HPA) system, (2) improve disturbances of the autonomous nervous system, and (3) dampen the aggregability of platelets. There is only limited information about the influence of acute treatment with SSRIs on these systems, which is especially important for the initiation of therapy in high-risk cardiac patients. We compared the reaction of these systems to physical stress with single-dose SSRI treatment (100 mg) with that of placebo treatment.


METHODS
Using a double-blind, crossover, placebo-controlled design, we assessed HPA system activity via serum cortisol and corticotropin as well as sympathetic nervous system by determining serum norepinephrine and epinephrine levels at baseline and as a response to stress. Analysis of heart rate variability (HRV) provided information on sympathetic/parasympathetic balance. Platelet activity was measured via flow-cytometric determination of platelet surface activation markers along with the serotonin (5-HT) uptake of platelets.


RESULTS
We studied 12 healthy young men under placebo and verum conditions. We found higher HPA system activity at baseline and after physical activity under sertraline when compared with placebo, no difference in sympathetic nervous system activity after physical exertion and only slightly heightened baseline epinephrine values after sertraline intake. No difference was seen between sertraline and placebo intake regarding platelet activity and 5-HT uptake, HRV, blood pressure, and HR.


CONCLUSIONS
Initiating sertraline treatment increases HPA system activity and epinephrine concentrations. We found no clinically relevant effect of single-dose sertraline treatment on autonomous nervous function, platelet activity, or platelet 5-HT uptake. These findings may not be extrapolated to patients with affective or cardiac disorders or to other SSRIs.
Ahrens
Thorben
T
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany.
Frankhauser
Pascal
P
Lederbogen
Florian
F
Deuschle
Michael
M
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001341:Autonomic Nervous System / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D005080:Exercise Test / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D015539:Platelet Activation / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D020280:Sertraline / Q000008:administration & dosage / Q000494:pharmacology*; D016683:Supine Position / Q000502:physiology
D000324:Adrenocorticotropic Hormone; D004837:Epinephrine; D006854:Hydrocortisone; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline