Antidepressants such as SSRIs work by enhancing neuroplasticity and connectivity in the brain, offering new insights into their role in treating depression beyond the serotonin theory. Credit: SciTechDaily.com
The serotonin-enhancing effects of antidepressants are essential and relieve depression by restoring normal communication and connections in the brain.
New research highlights that SSRIs and other antidepressants treat depression not by correcting serotonin imbalances but by promoting neuroplasticity and improving communication in a brain region, reshaping the clinical debate about their effectiveness.
New research on antidepressants
Researchers at the University of Colorado Anschutz Medical Campus have created a new framework for understanding how classic antidepressants work in the treatment of major depressive disorder (MDD), reemphasizing their importance and aiming to reframe the clinical conversation about their role in treatment.
The nature of the dysfunction at the root of MDD has been under investigation for decades. Classic antidepressants like SSRIs (selective serotonin reuptake inhibitors like Prozac and Zoloft) cause levels of the brain’s chemical messenger, serotonin, to increase. This observation led to the idea that antidepressants work because they restore a chemical imbalance, such as a lack of serotonin. However, subsequent years of research have not shown any significant decrease in serotonin in people with depression. While experts have moved away from this hypothesis due to a lack of concrete evidence, it has led to a shift in public opinion about the effectiveness of these drugs.
A new framework for understanding the treatment of MDD
However, antidepressants such as SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs) are still effective in alleviating depressive episodes in many patients. In an article published in Molecular psychiatry, researchers outline a new framework for understanding how antidepressants are effective in treating MDD. This framework helps explain how antidepressants such as SSRIs are still useful even when MDD is not due to serotonin deficiency.
“The best evidence of brain changes in people with MDD is that some areas of the brain are not communicating normally,” says Scott Thompson, PhD, a professor in the Department of Psychiatry at the University of Colorado School of Medicine and a senior. author. “When the parts of the brain responsible for reward, happiness, mood, self-esteem, and in some cases, problem solving, don’t communicate properly, then they can’t do their job properly.
The role of neuroplasticity in the treatment of MDD
“There is good evidence that antidepressants that increase serotonin, such as SSRIs, all work by restoring the strength of connections between these areas of the brain. So are new therapeutics such as esketamine and psychedelics. This form of neuroplasticity helps release brain circuits from being ‘stuck’ in a pathological state, ultimately leading to the restoration of healthy brain function,” said Thompson.
Thompson and colleagues liken the theory to a car that goes off the road and gets stuck in a ditch, requiring the help of a tow truck to pull the car out of its stuck state and allow it to move freely on the road again.
Implications for clinical practice
The researchers hope that health care providers will use their examples to strengthen conversations with patients who fear these treatments and help them better understand their condition and how to treat it.
“We hope this framework will provide clinicians with new ways to communicate how these treatments are working to combat MDD,” said C. Neill Epperson, MD, Robert Freedman Endowed Professor and Chair of the Department of Psychiatry at the University of Colorado School of Medicine and co-author on the paper.
“Much of the public conversation about the effectiveness of antidepressants and the role of serotonin in diagnosis and treatment has been negative and largely dangerous. While MDD is a heterogeneous disorder with no one-size-fits-all solution, it’s important to emphasize that if treatment or medication works for you, it’s life-saving. Understanding how these drugs promote neuroplasticity can help reinforce this message.”
Reference: “Beyond the serotonin deficit hypothesis: communicating a neuroplasticity framework of major depressive disorder” by Chloe E. Page, C. Neill Epperson, Andrew M. Novick, Korrina A. Duffy, and Scott M. Thompson, 31 May 2024, Molecular psychiatry.
DOI: 10.1038/s41380-024-02625-2