Our prospective study does not support the assumption that paroxetine can cause a prolonged PFA-closure (bleeding) time during paroxetine therapy due to a serotonin transporter polymorphism. Old age, use of platelet inhibitors and a history of gastrointestinal bleeding remain the focus for SSRI-induced bleeding complications.
Selective Serotonin Reuptake Inhibitors (SSRIs) are the most commonly used antidepressants. From case reports and observational studies it has become clear that treatment with SSRIs can leadto bleeding mostly from the upper gastrointestinal tract (gullet and stomach). But also bruising is frequently complained of. The most likely mechanism is the prevention of serotonin uptake in blood platelets. Platelets, or thrombocytes, are the cells circulating in the blood that are involved in the formation of blood clots to stop bleeding. Prevention of serotonin uptake into the platelets by SSRIs can lead to insufficient functioning of the platelets resulting in longer bleeding time.
The serotonin transporter gene is responsible for the uptake of serotonin in the brain but also in platelets. This gene is also believed to play an important role with environmental stress in causing depression. It has been shown that the serotonin transporter gene is polymorphic.The polymorphism that is considered most relevant is an insertion/deletion polymorphism in the promoter region of the gene, which encodes for the serotonin transporter.
The serotonin transporter gene (5-HTTLPR) gene has two variant alleles: a short (S) and a long (L) allele. The S allele has been associated with a nearly 50% reduction in expression of the serotonin transporter protein, vulnerability for mood disorders, inadequate response to SSRIs and side-effects.
In Whites, the genotype frequencies are approximately 25% SS, 47% SL and 28% LL
43 patients were eligible they had been using paroxetine for at least 4 weeks and were aged between 18 and 70 years.
Patients did not differ in bleeding time, bruising and mild spontaneous bleeding events between patients with different types of genes for the 5-HTTLPR gene.
So this study suggests that the association between SSRI therapy and prolonged bleeding time may not be related to the polymorphism of the serotonin transporter (5-HTTLPR) investigated.
Old age, use of platelet inhibitors, NSAIDs and a history of gastrointestinal bleeding remain the focus for SSRI-induced bleeding complications.
Dahlia M. C. Hougardy, Toine C. G. Egberts, Fedde van der Graaf, Vincent J. Brenninkmeijer, Luc J. J. Derijks (2008). Serotonin transporter polymorphism and bleeding time during SSRI therapy British Journal of Clinical Pharmacology, 65 (5), 761-766 DOI: 10.1111/j.1365-2125.2008.03098.x