Clinical impact of selective serotonin reuptake inhibitors therapy with bleeding risks

Duke University, Durham, North Carolina, United States
Journal of Internal Medicine (Impact Factor: 6.06). 04/2007; 261(3):205-13. DOI: 10.1111/j.1365-2796.2006.01720.x
Source: PubMed


The selective serotonin reuptake inhibitors (SSRIs) are extensively used for the treatment of multiple psychiatric conditions. In vitro and ex vivo data with these agents indicate they may have varying degrees of antiplatelet activity via multiple receptors. Reports of bleeding in patients receiving SSRIs appeared soon after their introduction. A review of the literature suggests SSRI therapy may increase the risk of bleeding especially with concomitant aspirin or nonsteroidal anti-inflammatory agents. Clinicians should exercise caution when prescribing these agents in high risk patients and maintain awareness of the potential contribution of SSRIs to unexplained bleeding episodes.

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    • "A lower dissociation constant reflects a higher affinity for the serotonin transporter which is associated with higher inhibition of serotonin reuptake and therefore more elevated extracellular serotonin levels at pre-synaptic junctions (Tatsumi et al., 1997; Meijer et al., 2004). Of the SSRI antidepressants, paroxetine, sertraline, and fluoxetine are the three most potent (high) inhibitors of serotonin reuptake, while citalopram and fluvoxamine can be classified as relatively lower inhibitors (Tatsumi et al., 1997; van Walraven et al., 2001; Meijer et al., 2004; Turner et al., 2007). "
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    ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs) are a widely prescribed class of antidepressants. Laboratory and epidemiologic evidence suggests that a prolactin-mediated mechanism secondary to increased serotonin levels at neuronal synapses could lead to a potentially carcinogenic effect of SSRIs. In this population-based case-control study, we evaluated the association between SSRI use and breast cancer risk as a function of their relative degree of inhibition of serotonin reuptake as a proxy for their impact on prolactin levels. Cases were 2,129 women with primary invasive breast cancer diagnosed from 2003 to 2007, and controls were 21,297 women randomly selected from the population registry. Detailed information for each SSRI prescription dispensed was compiled using the Saskatchewan prescription database. Logistic regression was used to evaluate the impact of use of high and lower inhibitors of serotonin reuptake and duration of use, as well as to assess the effect of individual high inhibitors on the risk of breast cancer. Exclusive users of high or lower inhibitors of serotonin reuptake were not at increased risk for breast cancer compared with non-users of SSRIs (OR = 1.01, CI = 0.88-1.17 and OR = 0.91, CI = 0.67-1.25 respectively), regardless of their duration of use or menopausal status. While we cannot rule out the possibility of a clinically important risk increase (OR = 1.83, CI = 0.99-3.40) for long-term users of sertraline (≥24 prescriptions), given the small number of exposed cases (n = 12), the borderline statistical significance, and the wide confidence interval, these results need to be interpreted cautiously. In this large population-based case-control study, we found no conclusive evidence of breast cancer risk associated with the use of SSRIs even after assessing the degree of serotonin reuptake inhibition and duration of use. Our results do not support the serotonin-mediated pathway for the prolactin-breast cancer hypothesis.
    Full-text · Article · Dec 2012 · Frontiers in Oncology
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    • "In general the risk of bleeding with SSRI treatment is low (Serebruany, 2006; Reeves et al., 2007). However, the risk of bleeding is increased with concomitant use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) (Yuan et al., 2006; Turner et al., 2007). Two studies found that the risk for an upper gastrointestinal bleed from the concurrent use of NSAIDs or low-dose aspirin with a SSRI exceeded the additive risk of the agents alone (Mort et al., 2006). "
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    ABSTRACT: Although the selective serotonin reuptake inhibitors (SSRIs), which are now widely used as a first-line treatment for depression and many other psychiatric conditions, are generally well tolerated, they are not devoid of side effects. Most short-term treatment-related side effects of SSRIs are transient and disappear after a few days or weeks. However, following long-term treatment with the SSRIs, some serious adverse events may occur. Some of them can be difficult to recognise because they can resemble residual symptoms of depression. The most serious can be life threatening. They all have a negative influence on the patient's quality of life and are frequently a prime reason for a lack of long-term compliance with the associated increased risk of recurrence of a depressive episode. This article is an overview of the more common adverse events, which are seen with non-acute treatment with the SSRIs.
    Preview · Article · Nov 2009 · Journal of Psychopharmacology
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