Use of selective serotonin reuptake inhibitors is associated with very low plasma-free serotonin concentrations in humans

Abstract

Background Selective serotonin reuptake inhibitors (SSRIs) block the serotonin transporter on neurons, but also on platelets, thus decreasing platelet serotonin concentrations in users of SSRIs. Data on plasma-free serotonin concentrations in SSRI users are lacking, while plasma-free serotonin is available for receptor binding and plays a role in several pathophysiological processes. We therefore measured the plasma-free and platelet serotonin concentrations in users of SSRIs and age-matched healthy controls, and we analysed plasma concentrations of the serotonin precursor tryptophan and serotonin metabolite 5-hydroxyindoleamineacetic acid (5-HIAA). Methods For this cross-sectional single-centre case control study, participants were recruited at the departments of Psychiatry and General Medicine. High-performance liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) was used to measure plasma-free and platelet serotonin, plasma tryptophan and 5-HIAA concentrations. Preanalytical conditions were optimized by careful blood collection, rapid sample handling, high-speed centrifugation, drug and diet restrictions and age-matched controls. Results In 64 SSRI users, median concentrations of plasma-free and platelet serotonin were 10-fold and 14-fold lower, respectively, than in 64 matched controls. Patients using higher dose SSRIs or those with higher affinity for the serotonin transporter had lower plasma-free and platelet serotonin concentrations. Compared with controls, SSRI users had similar median plasma tryptophan concentrations but slightly higher plasma 5-HIAA concentrations. Conclusion SSRI users have low platelet serotonin and low plasma-free serotonin. This could not be explained by lower concentrations of its precursor tryptophan, and only partially by increased breakdown to 5-HIAA.