Platelet reactivity in depressed patients treated with paroxetine: preliminary findings.
BACKGROUND
Alterations in platelet reactivity have been previously posited to underlie the increased vulnerability of patients with depression to ischemic heart disease (IHD). The present study sought to determine whether the increased platelet reactivity associated with major depression is reduced after antidepressant treatment.


METHODS
Patients diagnosed as having DSM-IV major depression (n = 15) (mean age, 37 +/- 7 years; range, 23-48 years) and 12 normal comparison subjects (mean age, 36 +/- 7; range, 23-48 years) were recruited. None of the controls or depressed group had evidence of IHD; 10 of 15 patients who were depressed had 1 or more traditional IHD risk factors. In vivo platelet activation, secretion, and dose-response aggregation of the controls and patients was measured after overnight bedrest under basal conditions, and after a mild exercise challenge. After 6 weeks of open-label treatment with the selective serotonin reuptake inhibitor paroxetine (20 mg/d), the patients with depression were readmitted and procedures of the first General Clinical Research Center admission repeated.


RESULTS
In comparison with the control group, the depressed group exhibited greater procoagulant activity as detected by increased platelet binding of the monoclonal antibodies anti-ligand-induced binding site and GA6, and increased plasma concentrations of platelet factor 4 under basal conditions. After paroxetine treatment, the patients with depression exhibited significant reductions in all 3 parameters.


CONCLUSIONS
Normalization of platelet activation is associated with paroxetine treatment of patients with depression. Because this study design did not allow for the determination of whether this effect of paroxetine on platelet function is caused by a direct effect of the drug or placebo or, alternatively, because of recovery from depression, studies containing a placebo and/or psychotherapy treatment arm may resolve this issue.
Musselman
D L
DL
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Dr, Suite 4000, Atlanta, GA 30322, USA.
Marzec
U M
UM
Manatunga
A
A
Penna
S
S
Reemsnyder
A
A
Knight
B T
BT
Baron
A
A
Hanson
S R
SR
Nemeroff
C B
CB
D000255:Adenosine Triphosphate / Q000378:metabolism; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D017374:Paroxetine / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000378:metabolism; D005082:Physical Exertion / Q000502:physiology; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D010978:Platelet Factor 4 / Q000378:metabolism; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors; D012044:Regression Analysis; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D001620:beta-Thromboglobulin / Q000378:metabolism
D000255:Adenosine Triphosphate; D017374:Paroxetine; D010446:Peptide Fragments; D010978:Platelet Factor 4; D018179:Receptors, Thrombin; D017367:Selective Serotonin Reuptake Inhibitors; D001620:beta-Thromboglobulin; C072032:thrombin receptor peptide (42-55)