Long Island Neurocare Therapy
Long Island Neurocare Therapy

Why are Antidepressants NOT the Answer for Everybody?

Doctors frequently prescribe specific types of antidepressants, but several studies have revealed a biological explanation for why some individuals with depression do not respond to those antidepressants. Their non-response is due to underlying differences in the nerve cells that create and use serotonin.

Serotonin is the chemical messenger that has the most significant impact on feelings of happiness and well-being.

Scientists have persistently been suspicious that interruption in serotonin brain circuits is crucial in major depressive disorder. Therefore, selective serotonin reuptake inhibitors (SSRI) are antidepressant drugs used to remedy this disruption by increasing serotonin levels at nerve junctions.

Nevertheless, for reasons still unclear, SSRI antidepressants do not work for about thirty percent of individuals suffering from major depression. Now, investigators at the Salk Institute for Biological Studies, based in La Jolla, California, and the Mayo Clinic in Rochester, may have solved the mystery.

An article in Molecular Psychiatry describes how, by studying cells from hundreds of individuals suffering from depression, the research team discovered differences that could explain resistance to SSRI antidepressants.

These results contribute a new way of examining, understanding, and addressing depression. In addition, investigators believe their findings also offer insights into other psychiatric illnesses disrupting the brain’s serotonin system, such as schizophrenia and bipolar disorder.


Depression is a leading cause of disability affecting individuals of all ages and significantly contributes to the global disease burden. The United Nations agency estimates that about three hundred million individuals live with this widespread psychiatric condition worldwide.

For the last study, scientists took skin cells from more than eight hundred individuals with major depressive disorder and converted them into stem cells.

Subsequently, they induced the stem cells to mature into “serotonergic neurons,” nerve cells forming the brain circuitry for producing and using serotonin.

Why are Antidepressants NOT the Answer for Everybody?

The team of scientists compared the serotonergic neurons of “SSRI antidepressants non-responders” with those of “SSRI antidepressants responders.” Non-responders were those individuals suffering from depression whose symptoms showed no improvement, while responders were those whose symptoms showed the most dramatic improvement to SSRI antidepressant treatment.

In previous research, investigators had shown that the cells of non-responders to SSRI antidepressants had more serotonin receptors, which caused an overreaction to the chemical messenger.


New studies explored a different facet of SSRI antidepressant unresponsiveness at the cellular level. It found no variations between SSRI-responsive and unresponsive cells in terms of serotonin biochemistry. However, the study revealed some underlying structural variations in the cells.

The development of the nervous system relies on tight control of neurite outgrowth. According to a 2018 study, interrupting this process can lead to neurological and developmental imbalances.

The team of scientists found that the nerve cells of SSRI antidepressant non-responders had much longer neurites than those of SSRI antidepressant responders. In genetic analysis, they also found a much weaker presence of PCDHA6 and PCDHA8 genes in the non-responders.

These two genes mentioned above are from the protocadherin family and play a central role in developing nerve cells and brain circuits.

When they muted PCDHA6 and PCDHA8 genes in healthy serotonergic neurons, the investigators found that these also developed abnormally long neurites, as did the nerve cells of SSRI antidepressant non-responders.

Having neurites of the wrong length may interrupt communication in serotonin brain circuitry, with some areas having too much transit and others not quite. This event could explain, according to the team of scientists, why SSRI antidepressants sometimes fail to treat major depression.

These recent studies provide insight into this standard treatment and suggest that other drugs, such as serotonergic antagonists, may be additional options for some patients.

The team now intends to look closely at the function of the two protocadherin genes in SSRI antidepressant non-responders.

Antidepressants cannot cure depression but can help reduce anxiety, moodiness, and suicidal thoughts. They work by changing the way the brain uses chemicals to balance mood or cope with stress.

Individuals should seek the advice and support of their physician when planning to stop using antidepressants. Their physician will help make a plan that may include gradually reducing the dose, switching to another drug, or a non-invasive, safe treatment, such as TMS therapy.

Long Island Neurocare Therapy utilizes NeuroStar TMS Therapy technology to achieve remission for our patients not responding to pharmaceutical depression treatments, including antidepressants. TMS Therapy may be the answer if you or someone you care about is still suffering from clinical depression after multiple treatment attempts.

Treatment with TMS proves to be a great promise to the possibility of achieving remission in addition to a complete life after its procedure and not taking antidepressants anymore.

At Long Island Neurocare Therapy, your health and well-being are essential to our success. Contact us today. We are here for you.

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