Department of Physiology and Pharmacology, Tel Aviv University, Tel Aviv 69978, Israel.
Beer Yaakov-Ness Ziona Mental Health Center, Beer Yaakov, Tel Aviv University, Tel Aviv 69978, Israel.
J Affect Disord. 2012 Jan;136(1-2):99-103. doi: 10.1016/j.jad.2011.08.013. Epub 2011 Sep 4.
Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) reduces the risk and severity of cardiovascular diseases. SSRIs block the serotonin transporter, thereby inhibiting serotonin (5-HT) uptake into presynaptic neurons as well as into platelets where 5-HT is stored in dense granules. When 5-HT is released in response to agonists it enhances platelet aggregation induced by injury-related signals. Chronic administration of SSRIs may thus reduce platelet aggregability secondary to depletion of platelets' serotonin stores.
The study included ten DSM-IV-TR major depression (MDD) and four obsessive compulsive disorder (OCD) patients and fourteen healthy untreated age- and sex-matched controls. The patients were chronically medicated (6-108 months) with various SSRIs. Platelet serotonin content was assessed in fresh samples of platelet rich plasma (PRP) using radioimmunoassay. ADP, collagen, arachidonic acid and epinephrine were used as inducers of platelet aggregation measured in PRP by turbometric method in a microplate reader.
Lower platelet serotonin content (66%; p<0.05) and lower ADP, collagen or epinephrine-induced platelet aggregation (10-52%; p<0.05) were detected in PRP of SSRI-medicated patients, while no such effect was obtained with arachidonic acid.
The small sample size and the co-treatment with non-SSRI drugs such as benzodiazepines.
Patients chronically medicated with SSRIs exhibit lower platelet 5-HT content and reduced platelet aggregation induced by ADP, collagen and epinephrine, but not by arachidonic acid. Our observations may explain the increased bleeding risk associated with chronic SSRI treatment as well as the reported beneficial effect of SSRIs in prevention of recurrent myocardial infarction.
慢性使用选择性 5-羟色胺再摄取抑制剂（SSRIs）可降低心血管疾病的风险和严重程度。SSRIs 阻断 5-羟色胺转运体，从而抑制 5-羟色胺（5-HT）进入突触前神经元和血小板，5-HT 储存在血小板致密颗粒中。当 5-HT 被激动剂释放时，它会增强与损伤相关信号诱导的血小板聚集。因此，SSRIs 的慢性给药可能会由于血小板 5-HT 储存耗尽而降低血小板聚集性。
该研究纳入了 10 名 DSM-IV-TR 重性抑郁障碍（MDD）和 4 名强迫症（OCD）患者以及 14 名未经治疗的健康、年龄和性别匹配的对照者。患者接受各种 SSRIs 的慢性治疗（6-108 个月）。使用放射免疫分析法评估富含血小板的血浆（PRP）中血小板 5-HT 含量。ADP、胶原、花生四烯酸和肾上腺素被用作诱导剂，通过微板阅读器中的涡轮光度法在 PRP 中测量血小板聚集。
SSRIs 治疗的患者 PRP 中的血小板 5-HT 含量较低（66%；p<0.05），ADP、胶原或肾上腺素诱导的血小板聚集率较低（10-52%；p<0.05），而花生四烯酸则没有这种作用。
样本量小，以及与苯二氮䓬类等非 SSRIs 药物的联合治疗。
慢性使用 SSRIs 治疗的患者血小板 5-HT 含量较低，ADP、胶原和肾上腺素诱导的血小板聚集减少，但花生四烯酸诱导的血小板聚集没有减少。我们的观察结果可以解释与慢性 SSRIs 治疗相关的出血风险增加，以及 SSRIs 预防复发性心肌梗死的报告有益效果。
