Platelet hyperactivity in clinical depression and the beneficial effect of antidepressant drug treatment: How strong is the evidence?

Department of General Internal Medicine, University Hospital, CH-3010 Bern, Switzerland.
Acta Psychiatrica Scandinavica (Impact Factor: 5.61). 10/2004; 110(3):163-77. DOI: 10.1111/j.1600-0447.2004.00308.x
Source: PubMed


Platelet hyperactivity is thought to contribute to the increased coronary artery disease (CAD) risk in depression. This study reviewed the evidence for hyperactive platelets and for effects of antidepressant drug treatment on platelet 'stickiness' in clinical depression.
By means of PubMed electronic library search, 34 studies in English were identified (1983-2003) and critically reviewed.
In depression, flow cytometry studies allowing detection of subtle platelet activation states consistently found at least one platelet activation marker to be increased, while the bulk of platelet aggregation studies did not suggest increased platelet aggregability. Platelets seem to be more activated in depressed patients with CAD than in depressed individuals without CAD. The selective serotonin reuptake inhibitors normalized platelet hyperactivity in four studies.
Data on platelet activity in depression are inconclusive. To resolve this issue and its clinical implications, studies in larger sample sizes controlling for confounders of platelet functioning and prospectively designed are needed.

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    • "Antipsychotic drugs are widely used in the treatment of various mental disorders; however, a lot of their side effects, including cardiovascular diseases with blood platelet dysfunction, have been reported (Thommassen et al. 2001; De Clerck et al. 2004; von Kanel 2004; Mö ller 2004; Yang et al. 2004; Dietrich-Muszalska et al. 2005; Numata et al. 2005). The antipsychotic drugs used in the therapy of schizophrenia may affect blood platelet activity and their aggregability (Yao et al. 1994). "
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    ABSTRACT: Blood platelets play an important role in haemostasis and their hyperaggregability may lead to thrombosis and cardiovascular diseases. Increased incidence of mortality, caused by cardiovascular disease, and the increased risk of thrombotic complication in schizophrenic patients treated with antipsychotics have been reported. The effects of antipsychotic drugs on blood platelet function are not fully explained, therefore the purpose of the present study was to examine and compare the effects of the second-generation antipsychotic drugs used in schizophrenia (clozapine, risperidone and olanzapine), with the effects of the first generation antipsychotic, haloperidol, on the platelet aggregation induced by ADP in vitro. Blood obtained from healthy volunteers (n=25) collected into sodium citrate was centrifuged (250xg, 10 min) at room temperature to obtain platelet-rich plasma. Aggregation of blood platelets (10 microM ADP) was recorded (Chrono-log aggregometer) in platelet-rich plasma preincubated with antipsychotic drugs (final concentration: clozapine 420 ng/ml, risperidone 65 ng/ml, olanzapine 40 ng/ml, haloperidol 20 ng/ml) for 30 min. Our results showed that all tested drugs inhibit platelet aggregation induced by ADP in vitro. Among studied antipsychotic drugs clozapine and olanzapine significantly reduced platelet aggregability in vitro. In comparison with control platelets (without the drug), clozapine inhibited ADP-induced platelet aggregation by 21% (P=3.7x10(-6)) and olanzapine by 18% (P=2.8x10(-4)), respectively. The obtained results indicate that antipsychotic drugs, especially clozapine and olanzapine, contrary to haloperidol, reduced response of blood platelets to ADP measured as platelet aggregation. This suggests that therapy with such antipsychotics, particularly with second-generation antipsychotics, may partly reduce prothrombotic events associated with the increased platelet activation observed in schizophrenic patients. The mechanism of antiaggregatory influence of antipsychotics requires further studies.
    The World Journal of Biological Psychiatry 03/2010; 11(2 Pt 2):268-75. DOI:10.3109/15622970802505792 · 4.18 Impact Factor
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    • "These biological factors include decreased heart rate variability (Carney et al., 2001), increased sympathetic nervous system activity (Otte et al., 2005), hyperactivity of the hypothalamic–pituitary–adrenocortical system (Otte et al., 2004), increased secretion of pro-inflammatory cytokines, and potential toxicity of psychotropic medications (Bingefors et al., 1996). Because serotonin dysregulation has a central role in both major depression and platelet activation (Willerson et al., 1989; Smith et al., 1997; Nemeroff and Musselman, 2000; Schins et al., 2003; von Kanel, 2004), increased platelet activation has also been identified as a potential link between depression and CHD. Previous studies have reported an association between major depression and increased plasma concentrations of the plateletspecific , alpha granule secretory proteins, platelet factor 4 (PF4) and β-thromboglobulin (β-TG) in a number of populations including patients with acute coronary heart syndrome (Kuijpers et al., 2002; Laghrissi-Thode et al., 1997; Musselman et al., 2000; Serebruany et al., 2003c; Whyte et al., 2001). "
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    ABSTRACT: Depression is associated with increased morbidity and mortality in patients with coronary heart disease (CHD). Increased platelet activation has been proposed as a potential mechanism by which depression may lead to adverse cardiovascular outcomes. In this cross-sectional study, we measured platelet activation in 104 patients with stable CHD, including 58 with a current episode of major depression and 46 without past or current major depression. Participants were instructed not to take aspirin for 7 days prior to the study appointment. Platelet activation was measured by plasma concentrations of platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG), and by 24-h urinary concentrations of 11-dehydro-thromboxane B(2) (TBXB2). We observed no differences in the mean levels of PF4, B-TG or TBXB2 in patients with and without major depression. Results were unchanged after adjustment for age, smoking, use of aspirin, and use of any psychotropic medication. We found no evidence of an association between major depression and platelet activation as measured by plasma concentrations of PF4 and beta-TG, or urinary TBXB2 in 104 outpatients with stable CHD. These findings do not support a role for platelet activation in the association between depression and cardiovascular disease among patients with stable CHD.
    Psychiatry Research 02/2010; 175(3):200-4. DOI:10.1016/j.psychres.2009.01.010 · 2.47 Impact Factor
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    • "Depression is a major risk factor for cardiovascular morbidity and mortality (Musselman et al., 1998; Nair et al., 1999; Carney et al., 2002). It has been suggested that the increased mortality related to depressive states after a myocardial infarction may be induced by an increased activation of the hypothalamic–pituitary–adrenal axis (Stokes, 1995), a possible cardiotoxicity due to side effects of antidepressant drugs (Dziukas and Vohra, 1991; McKinney and Rasmussen, 2003; Von Kanel, 2004), or abnormalities in platelet function (Markovitz and Matthews, 1991; Carney et al., 2002). "
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    ABSTRACT: Depression is considered an important risk factor in patients with cardiovascular disease (CVD). Although the biological mechanism is unknown, it has been suggested that hyperactivity of platelets may have an important role in the onset and evolution of cardiovascular damage. The goals of this study were to evaluate by transmission electron microscopy and immunohistochemistry the presence of ultra-structural variations in platelets from individuals with recent diagnosis of major depression disease (MDD, patients without previous anti-depressant treatment and from healthy control subjects.). Platelets from depressed patients had a greater proportion of dendritic forms compared with those obtained from control subjects. Morphological changes, such as dilation of open canalicular and dense tubular systems, platelet vacuolization, electrodense pattern of membranes, and a different immunolocalization of P-selectin were observed in the platelets from depressed patients compared with those isolated from healthy subjects. Our results revealed ultra-structural changes in platelets isolated from patients with MDD suggestive of enhanced platelet activation.
    Psychiatry Research 02/2010; 176(2-3):179-82. DOI:10.1016/j.psychres.2009.07.021 · 2.47 Impact Factor
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