Effects of Sertraline on Platelet Functioning in Depressed Patients
July 1, 2000
Effects of Sertraline on Platelet Functioning in Depressed Patients
Abstract & commentary
Source: Markovitz JH, et al. Platelet activation in depression and effects of sertraline treatment: An open-label study. Am J Psychiatry 2000;57:1006-1008.
One of the interesting biologic findings in the link between depression and cardiovascular disease has been that depressed patients exhibit a greater amount of platelet activation when compared to euthymic (nondepressed) patients. Such an effect on platelets may well contribute to the development, or worsening, of endothelial damage to coronary vasculature, and hence the increased mortality rates after myocardial infarction among depressed patients.
To date, there remain questions regarding the effect of treating depression (particularly with serotonergic agents) on platelet activation. The current report examined the effects of sertraline (Zoloft) on platelet activation in depressed patients. Markovitz and colleagues tested depressed patients (n = 21, age 25-52) and 21 sex- and age-matched comparison subjects. All patients were free from antidepressant or anxiolytic use for at least four months before testing. In addition, patients had not received any drugs within the previous two weeks, which could affect platelet functioning. Subjects with significant medical or other psychiatric disease were excluded. Depressed subjects were screened over the phone by interviewers using the 21-item Hamilton Depression Rating Scale. Subjects who scored 20 or higher were then interviewed in an office visit with the Primary Care Evaluation of Mental Disorders (PRIME-MD) and the Beck Depression Inventory (BDI). Subjects with a BDI score of 10 or higher and a diagnosis of major depressive episode according to the PRIME-MD were evaluated by a psychiatrist using a repeat Hamilton depression scale and clinical evaluation. Nondepressed comparison subjects were screened by using the PRIME-MD and BDI. Subjects whose BDI was less than 10 and did not exhibit depressive symptoms or anhedonia were considered nondepressed.
Depressed patients began taking 50 mg/d of sertraline after blood testing and were evaluated at three weeks; 11 of the 17 patients who returned for the second evaluation had their dose increased to 100 mg/d. (One patient started on 25 mg and increased to 50 mg at three weeks.) Aftersix weeks, 17 patients returned for repeat laboratory and Beck Depression Inventory testing.
Platelet activation measures were performed using AC1.2-PE for platelet secretion; anti-LIBS-1, specific for fibrinogen receptor binding; and annexin V, a marker of membrane procoagulant activity. For both groups, a family history of coronary heart disease (CHD) was taken, defining family history of CHD as a parent or grandparent with a CHD event or stroke before the age of 65.
Family history of CHD was present in 11 of the depressed patients vs. seven of the comparison subjects. Platelet secretion in response to collagen was higher among depressed patients. Contrary to previous reports in the literature, 5-HT receptor density (Bmax) was lower in depressed patients than in comparison subjects. Individuals with both depression and a family history of CHD had higher wound-induced fibrinogen receptor binding at one minute than the other subjects, although this did not achieve statistical significance (P = 0.06). After sertraline treatment, collagen-induced platelet secretion decreased. The only other platelet measure that was more than minimally changed was wound-induced procoagulant activity at 2 minutes; this, too, did not achieve statistical significance (P = 0.09). Regression analyses indicated that changes in platelet activation were not related to Bmax or platelet serotonin content, final sertraline dose, changes in BDI scores, or a BDI follow-up score of less than 10.
Comment by Michael F. Barber, PharmD
While the evidence for the link between CHD and depression is mounting in impressive fashion, some focus is needed on the therapeutic implications. As clinicians become increasingly aware of the importance of depressive symptoms regarding CHD risks, it is clear that screening and treatment for depression is important. But the effect of antidepressant treatment has not been established in terms of cardiovascular risk. One inherent question regarding the effect of antidepressant therapy on CHD risk is whether platelet activation is affected. Since the platelet activation is presumably due to the dysregulated serotoninergic system present in most depressed patients, it is intuitive that serotonergic antidepressants could affect this increased platelet activation. While this study attempted to answer this question, it seemed to suffer from a lack of an appropriate sample size that would be needed to detect clinically important changes in platelet activation after the treatment of depressed patients with sertraline. Some trends were noted in the direction of lowered platelet activation after sertraline treatment; thus, there is ample reason to further explore this research question.
At the present time, it is still important that clinicians screen for and treat depression in patients with CHD. However, several questions still remain that need resolution in order for patients with depression and/or CHD to be managed appropriately. First, would there be additional benefit in terms of lowering CHD risk by using serotonergic agents? Second, should depressed patients without documented symptoms of CHD and at least one other risk factor (i.e., smoking, family history, dyslipidemia, diabetes mellitus) be treated with aspirin or other agents for primary prevention of CHD? Lastly, should patients with subclinical depression (i.e., several depressive symptoms present but not sufficient for a diagnosis of major depression) receive antidepressant therapy not only for improvement in depressive symptoms but also as another form of primary prevention of CHD? Only time and well-designed clinical trials will be able to provide answers to these important questions.
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