A new study suggests common antidepressants help the cardiovascular system.
Researchers at Loyola University Medical Center say selective serotonin reuptake inhibitors (SSRIs) provide benefits by affecting the way platelets, small cells in the blood involved in clotting, clump together.
In a study of 50 adults, the researchers found that platelets were slower to clump together, or aggregate, in participants who were taking an SSRI to treat depression.
As depression is associated with an increased risk of cardiovascular disease, this finding could indicate a beneficial side effect for people who take SSRIs to treat depression, said Evangelos Litinas, MD, research associate in the Center’s pathology department.
SSRIs function to modulate the effect of serotonin in the brain. Neurotransmitters, like serotonin, are messages sent across the gap called the synapse between nerve cells in the brain. The cell sending the message, called the presynaptic cell, releases serotonin into the synapse. The serotonin is taken in by the receiving, postsynaptic cell, or taken back by the presynaptic cell.
In a depressed patient, the postsynaptic cell doesn’t take in enough serotonin and the message gets lost. To treat the depression, SSRIs decrease the ability of the presynaptic cell to reuptake the serotonin, leaving the message in the synapse longer and giving the postsynaptic cell a better chance of receiving the serotonin.
However, this blocking activity of SSRIs may have an effect on other cells in the body that require serotonin uptake.
Platelets, which are involved in blood clotting, absorb serotonin only once and use it for their activation in response to injury. When a blood vessel is injured in a healthy patient, their platelets are exposed to proteins that normally reside beneath the endothelium, the thin layer of cells lining blood vessel walls. These proteins activate the platelets and prompt them to send out finger-like projections that grab onto each other. This also activates the clotting system so that a clot will form at the wound site. This kind of platelet activation also occurs when blood vessel walls become inflamed in atherosclerosis (“hardening of the arteries”).
Once activated, the platelets release the contents of small packages that they carry called delta granules. These packages contain calcium, various energy-containing molecules, and serotonin. When the delta granules are released by activated platelets, the serotonin and other molecules work in the injured area to amplify the coagulation response.
However, Dr. Litinas and his team believe that in depressed patients who have an associated risk of cardiovascular problems, the blocking activity of SSRIs may have a side effect of preventing the serotonin uptake by platelets, making them less responsive to aggregation and thereby improving the patients’ cardiovascular health.
The team collected blood samples from each volunteer at the beginning of the protocol and again at the study’s fourth week and eighth week. After each blood draw, the team separated the blood into its components to obtain the platelet-rich plasma for study.
The researchers then treated all of the samples with platelet-activating substances and with saline, which does not activate platelets. They observed platelet activity and quantified the amount of aggregation in each sample by using an aggregometer, a machine that aims light into liquid samples.
Cells that do not aggregate tend to prevent light from getting all the way through a sample to the other side, whereas cells that aggregate form large clusters that sink down out of the way, allowing the light to shine through.
When the platelets from healthy volunteers were treated with platelet-activating substances at the 4-week time point, 95 percent of the cells aggregated. In contrast, the platelets of participants taking an SSRI showed only 37 percent aggregation, indicating that the SSRI had somehow inhibited or changed the platelets’ ability to clump together.
As the study progressed, the researchers noticed something peculiar: The platelets taken from SSRI-treated patients at the 8-week mark aggregated more than those drawn at the 4-week mark. This suggested that SSRIs have the greatest impact on preventing platelet activation early on in treatment.
Dr. Litinas and his team believe this may be because the body takes several weeks to start modulating SSRIs in the body. The team has extended the study to include samples drawn at the 12-week mark.
They will also conduct a study using another brand of SSRI.
“The reason we’re doing this is to better the lives of depressed patients,” said Dr. Litinas.
“There is clear evidence that depressed patients have a higher risk of cardiovascular disease, and we want to eliminate that. Since depression can be treated with an SSRI, maybe the cardiovascular disease risk can also be decreased.
“We want our patients to live longer and happier lives, without depression or the risk of heart problems.”