Advances in Understanding How SSRIs Work

This entry was posted in Mental Health on March 27, 2014 and modified on April 30, 2019

how-ssris-workThe Centers for Disease Control and Prevention says more than 20 million Americans experience depression significant enough to warrant medical treatment, and 11 percent of those over 12 years of age are given antidepressants. Selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed antidepressants in the nation. But the drugs are not without their shortfalls.

SSRIs take up to two months before they become effective and don’t work the same for every person. Finding the right antidepressant can mean months of trial and error along with unpleasant side effects. But researchers at Tel Aviv University may have uncovered a way to streamline the process with a specific gene that could predict if SSRI therapy will work for an individual.

SSRIs block the brain’s ability to reabsorb serotonin. This leaves serotonin more accessible to the brain cells which are responsible for chemical communication. When the brain is sending and receiving signals well, mood also improves. That, at least, is the theory behind SSRIs. The Israeli research seems to reveal otherwise.

One question that encumbers antidepressant therapy is why SSRIs are effective for some people and not for others. The study used 80 cell lines from a biobank known as the National Laboratory for the Genetics of Israeli Populations which were either most responsive or least responsive to the SSRI paroxetine.

Once they’d identified the most and least responsive cell groups, they took a look at the RNA profiles of the cells. They found that the most responsive cells had lower levels of the gene CHL1. The least responsive cell groups had higher levels of CHL1. Researchers applied paroxetine to the cells for the three weeks that the medication normally requires to take effect.

Investigators noticed that during this time gene ITGB3 production was increasing. It is believed that ITGB3 and CHL1 work together to create new neurons and new synapses within the brain. In other words, the genes create building blocks and then build bridges that improve brain signaling including in the brain area responsible for mood regulation.

If they’re right they have answered the question as to why SSRIs take at least three weeks before they take effect even though absorption is blocked in a matter of days. The answer is that it takes that long to construct bridges (synapses). The findings appear to contradict current theories about SSRIs, which says that it’s the blocked reabsorption of serotonin which improves mood.

Right now SSRIs are working for around 60 percent of depressed patients. Other types of antidepressants could prove highly effective for the remaining 40 percent, but a gene test like the one suggested in the study would eliminate the need for lengthy and often discouraging trial and error as standard practice. Clinical trials are still needed before the biomarker is validated, but hopes are high that a gene test could be in the future. If CHL1 proves to be an effective gene indicator, then one day a simple blood test could determine the most effective treatment.

Having this degree of precision in diagnosis could make personalized treatment a reality. The researchers are currently working to confirm their findings at the molecular level. If successful, further trials would include animal and then human subjects. The study is also exciting insofar as it has spawned parallel research into finding personalized treatment possibilities for those suffering with Alzheimer’s as well.

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