Serotonin transporter polymorphism and bleeding time during SSRI therapy.
BACKGROUND
From case reports it has become clear that selective serotonin reuptake inhibitors (SSRIs) can cause bleeding disorders. The causative mechanism is as yet unknown. Several publications have described the relationship between the serotonin transporter genotype and the prevalence of certain diseases such as depression, but few have focused on the relationship with side-effects of antidepressive drugs such as SSRIs.


CONCLUSIONS
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.


OBJECTIVE
Selective serotonin reuptake inhibitors (SSRIs), such as paroxetine, are associated with an increased risk of bleeding disorders, probably due to decreased platelet serotonin levels. Polymorphisms in the serotonin transporter gene (5-HTT) may influence the risk of SSRI-induced bleedings. The aim of this study was to investigate whether and to what extent the serotonin transporter polymorphism increases the bleeding time in paroxetine users.


METHODS
A prospective study, using routinely collected hospital and pharmacy data, was conducted among 43 patients between 18 and 70 years old and on >4 weeks of paroxetine therapy. The genotype for the serotonin transporter (5-HTTLPR), trough paroxetine levels, platelet function analyser (PFA)-closure time (collagen/epinephrine) and a complete blood count were assessed.


RESULTS
No significant difference was seen between the SS, SL, LL genotypes of the serotonin transporter and the PFA-closure time. None of the covariates had a significant influence on the association between the serotonin transporter polymorphism and the PFA-closure time. Age and von Willebrand factor showed the largest contribution, but not significant. No difference was seen between the PFA-closure time and the frequency of bruising and spontaneous bleedings between patients with at least one S allele and with the LL genotype.


CONCLUSIONS
Our prospective study does not support the assumption that paroxetine can cause a prolonged PFA-closure 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.
Hougardy
Dahlia M C
DM
Department of Clinical Pharmacy, Máxima Medical Center, Veldhoven, The Netherlands. dahliahougardy@hotmail.com
Egberts
Toine C G
TC
van der Graaf
Fedde
F
Brenninkmeijer
Vincent J
VJ
Derijks
Luc J J
LJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000378:metabolism* / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
D017374:Paroxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human