CU Anschutz researchers unravel antidepressant mechanism

The neuroplasticity perspective on depression.


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Researchers at the University of Colorado Anschutz Medical Campus have introduced a new framework for understanding how traditional antidepressants treat major depressive disorder (MDD). They highlight the importance of these medications and seek to change how clinicians discuss their role in treatment.

For years, researchers have explored the root cause of MDD. Classic antidepressants, like SSRIs (e.g., Prozac), increase levels of serotonin, a brain chemical. This led to the belief that these drugs work by correcting a chemical imbalance, such as low serotonin levels.

Recent research hasn’t found a significant serotonin decrease in people with depression, leading experts to doubt the “chemical imbalance” theory. Despite this, antidepressants like SSRIs and SNRIs remain effective for many patients.

Scott Thompson, a professor in the Department of Psychiatry at the University of Colorado School of Medicine, explains that in people with MDD, specific brain regions don’t communicate properly, affecting mood, happiness, and problem-solving.

Antidepressants like SSRIs and newer treatments like ketamine and psychedelics help restore these connections, promoting neuroplasticity. Thompson compares this to a car stuck in a ditch, needing a tow truck to get back on the road. He hopes healthcare providers will use this analogy to reassure patients about these treatments, helping them better understand their condition and treatment options.

Dr. C. Neill Epperson, co-author of the paper and chair of the Department of Psychiatry at the CU School of Medicine, said, “We hope this framework helps clinicians explain how these treatments fight MDD. Public talk about antidepressants and serotonin’s role has often been negative and risky. While MDD varies, effective treatments are life-saving. Knowing how these meds promote neuroplasticity reinforces that.”

In conclusion, researchers at CU Anschutz have provided fresh insights into how antidepressants function. Their work challenges previous beliefs about serotonin’s role and highlights the importance of promoting neuroplasticity in treating depression.

Journal reference:

  1. Page, C.E., Epperson, C.N., Novick, A.M. et al. Beyond the serotonin deficit hypothesis: communicating a neuroplasticity framework of major depressive disorder. Molecular Psychiatry. DOI: 10.1038/s41380-024-02625-2.