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 isc hemic heart disease (IHD). The present study sought to determine whether th e 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 depresse d had 1 or more traditional IHD risk factors. In vivo platelet activation, secretion, and dose-response aggregation of the controls and patients was m easured after overnight bedrest under basal conditions, and after a mild ex ercise challenge. After 6 weeks of open-label treatment with the selective serotonin reuptake inhibitor paroxetine (20 mg/d), the patients with depres sion were readmitted and procedures of the first General Clinical Research Center admission repeated. Results: In comparison with the control group, the depressed group exhibite d greater procoagulant activity as detected by increased platelet binding o f the monoclonal antibodies anti-ligand-induced binding site and GA6, and i ncreased plasma concentrations of platelet factor 4 under basal conditions. After paroxetine treatment, the patients with depression exhibited signifi cant reductions in all 3 parameters. Conclusions: Normalization of platelet activation is associated with paroxe tine treatment of patients with depression. Because this study design did n ot allow for the determination of whether this effect of paroxetine on plat elet function is caused by a direct effect of the drug or placebo or, alter natively, because of recovery from depression, studies containing a placebo and/or psychotherapy treatment arm may resolve this issue.