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Serotonin transporter polymorphism and bleeding time during SSRI therapy.

Dahlia M C Hougardy¹, Toine C G Egberts, Fedde van der Graaf

¹Department of Clinical Pharmacy, Máxima Medical Center, Veldhoven, The Netherlands. dahliahougardy@hotmail.com

British Journal of Clinical Pharmacology

|February 19, 2008

Summary

Selective serotonin reuptake inhibitors (SSRIs) may cause bleeding disorders. This study found no link between the serotonin transporter polymorphism and prolonged bleeding time in paroxetine users, suggesting other factors are involved.

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Area of Science:

Pharmacogenomics
Clinical Pharmacology
Hematology

Background:

Selective serotonin reuptake inhibitors (SSRIs) are associated with bleeding disorders, potentially due to altered platelet serotonin levels.
The role of serotonin transporter gene (5-HTT) polymorphisms in SSRI-induced bleeding risk is not well understood.

Purpose of the Study:

To investigate if serotonin transporter (5-HTTLPR) polymorphism influences bleeding time in patients using paroxetine.
To determine the extent to which this genetic variation impacts SSRI-related bleeding risks.

Main Methods:

A prospective study of 43 patients on paroxetine therapy.
Assessed 5-HTTLPR genotype, paroxetine levels, platelet function (PFA-closure time), and complete blood count.

Main Results:

No significant differences in PFA-closure time were observed across different 5-HTTLPR genotypes (SS, SL, LL).
Covariates, including age and von Willebrand factor, did not significantly influence the association.
No differences in bleeding time or frequency of bruising/bleeding were found between patients with S alleles and the LL genotype.

Conclusions:

The study does not support the hypothesis that 5-HTTLPR polymorphism causes prolonged PFA-closure time in paroxetine users.
Factors such as advanced age, use of platelet inhibitors, and a history of gastrointestinal bleeding are more likely contributors to SSRI-induced bleeding.