Antidepressants such as SSRIs work by increasing neuroplasticity and connectivity in the brain, offering a new perspective on their role in treating depression beyond the serotonin theory. Credit: SciTechDaily.com
The serotonin-enhancing action of antidepressants is essential and relieves 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 brain regions, reshaping the clinical debate about their effectiveness.
New research on antidepressants
Scientists 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 around their role in treatment.
The nature of the dysfunction underlying MDD has been the subject of research for decades. Classic antidepressants, such as SSRIs (selective serotonin reuptake inhibitors, such as Prozac and Zoloft) cause levels of the brain’s chemical messenger, serotonin, to rise. 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 a significant decrease in serotonin in people with depression. Although experts have moved away from this hypothesis due to a lack of concrete evidence, it has led to a change 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 relieving 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 if MDD is not caused by a lack of serotonin.
“The best evidence for brain changes in people with MDD is that some areas of the brain are not communicating with each other normally,” says Scott Thompson, PhD, professor in the Department of Psychiatry at the University of Colorado School of Medicine and senior author. “When the parts of the brain responsible for reward, happiness, mood, self-esteem, even problem-solving in some cases, don’t communicate with each other properly, then they can’t do their jobs properly.”
The role of neuroplasticity in the treatment of MDD
“There is good evidence that antidepressants that increase serotonin, such as SSRIs, work by restoring the strength of connections between these areas of the brain. As well as 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,” Thompson said.
Thompson and colleagues liken this 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, allowing it to move freely on the road again.
Implications for clinical practice
The researchers hope that healthcare providers will use their examples to aid conversations with anxious patients about these treatments, helping them better understand their condition and how to treat it.
“We hope this framework provides clinicians with new ways to communicate how these treatments are working to combat MDD,” said C. Neill Epperson, MD, Robert Friedman Professor and Chair of the Department of Psychiatry at the School of Medicine at University of Colorado and co-author of the report.
“Much of the public discussion surrounding the effectiveness of antidepressants and the role that serotonin plays in diagnosis and treatment has been negative and largely dangerous. Although MDD is a heterogeneous disorder with no one-size-fits-all solution, it is important to emphasize that if a treatment or medication works for you, it is life-saving. Understanding how these drugs promote neuroplasticity can help reinforce this message.
Reference: “Beyond the Serotonin Deficiency 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, May 31, 2024 . Molecular psychiatry.
DOI: 10.1038/s41380-024-02625-2
