November 23, 2016

Reducing antidepressants’ side effects

Vanderbilt investigators have discovered how antidepressant medicines that block serotonin uptake can increase bleeding risk.

by Mahesh Rao

Medicines used to treat depression, called selective serotonin reuptake inhibitors (SSRIs), can increase bleeding risk and bleeding time and disrupt platelet aggregation in the gastrointestinal tract. SSRIs prevent cells from taking up the neurotransmitter serotonin that has been released from cells by blocking the serotonin transporter (SERT). It is unclear how blocking SERT disrupts platelet aggregation.

Heidi Hamm, Ph.D., Ana Carneiro, Ph.D., and colleagues used pharmacological and genetic models to show that chronic SSRI treatment causes decreased levels of a serotonin receptor (5-HT2AR) on platelets. They showed that inhibiting SERT increases extracellular serotonin, which desensitizes the 5-HT2AR and reduces platelet activation.

These findings, reported in the Journal of Biological Chemistry, suggest a novel mechanism where prolonged use of SSRI medications results in reduced platelet aggregation. This provides useful insight into the effects of SSRIs and supports findings that drugs targeting the serotonin receptor may be used to reduce recurrent thrombosis by blocking platelet activation.

This research was supported by grants from the National Institutes of Health (MH090256, TR000445, TR000446, TR000447, MH084659) and by an American Heart Association Predoctoral Fellowship Award.

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