Summary: Researchers have developed a new framework explaining how antidepressants, like SSRIs, treat major depressive disorder (MDD) by restoring brain connectivity rather than correcting a serotonin imbalance.
Their findings emphasize the continued importance of these medications despite shifting public opinion. This new understanding could improve patient-clinician conversations about depression treatment.
Key Facts:
- Antidepressants like SSRIs and SNRIs restore connectivity between brain regions.
- New framework suggests antidepressants promote neuroplasticity, helping brain circuits recover.
- Study aims to reframe public and clinical perception of antidepressant efficacy.
Source: University of Colorado
Researchers from the University of Colorado Anschutz Medical Campus have established a new framework for understanding how classic antidepressants work in treating major depressive disorder (MDD), reemphasizing their importance and aiming to reframe clinical conversation around 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, such as Prozac) cause an elevation in the levels of the brain chemical messenger, serotonin.
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 showed no significant decrease in serotonin in people with depression. While experts have moved away from this hypothesis due to lack of concrete evidence, this has led to a shift in public opinion on the effectiveness of these medications.
Antidepressants, such as SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs) are still effective in alleviating depressive episodes in many patients, however.
In a paper published in Molecular Psychiatry, researchers outline a new framework for understanding how antidepressants are efficacious in treating MDD.
This framework helps clarify how antidepressants like SSRIs are still be helpful, even if MDD isn’t caused by a lack of serotonin.
“The best evidence of changes in the brain in people suffering from MDD is that some brain regions 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, are not communicating with each other properly, then they can’t do their jobs properly.
“There is good evidence that antidepressants that increase serotonin, like SSRIs, all work by restoring the strength of the connections between these regions of the brain. So do novel therapeutics such as esketamine and psychedelics.
This form of neuroplasticity helps release brain circuits from being ‘stuck’ in a pathological state, ultimately leading to a restoration of healthy brain function,” said Thompson.
Thompson and colleagues liken this theory to a car running off the road and getting 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 down the road again.
Researchers are hoping health care providers will use their examples to bolster conversations with apprehensive patients about these treatments, helping them better understand their condition and how to treat it.
“We are hoping this framework provides clinicians new ways to communicate the way these treatments work in combating MDD,” said C. Neill Epperson, MD, Robert Freedman endowed professor and chair of the department of psychiatry in the University of Colorado School of Medicine and co-author on the paper.
“Much of the public conversation around the effectiveness of antidepressants, and the role serotonin plays in diagnosis and treatment, has been negative and largely dangerous.
“While MDD is a heterogenous disorder with no one fits all solution, it is important to emphasize that if a treatment or medication is working for you, then they are lifesaving. Understanding how these medications promote neuroplasticity can help strengthen that message.”
About this psychopharmacology and depression research news
Author: Kelsea Pieters
Source: University of Colorado
Contact: Kelsea Pieters – University of Colorado
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Beyond the serotonin deficit hypothesis: communicating a neuroplasticity framework of major depressive disorder” by Scott Thompson et al. Molecular Psychiatry
Abstract
Beyond the serotonin deficit hypothesis: communicating a neuroplasticity framework of major depressive disorder
The serotonin deficit hypothesis explanation for major depressive disorder (MDD) has persisted among clinicians and the general public alike despite insufficient supporting evidence.
To combat rising mental health crises and eroding public trust in science and medicine, researchers and clinicians must be able to communicate to patients and the public an updated framework of MDD: one that is (1) accessible to a general audience, (2) accurately integrates current evidence about the efficacy of conventional serotonergic antidepressants with broader and deeper understandings of pathophysiology and treatment, and (3) capable of accommodating new evidence.
In this article, we summarize a framework for the pathophysiology and treatment of MDD that is informed by clinical and preclinical research in psychiatry and neuroscience.
First, we discuss how MDD can be understood as inflexibility in cognitive and emotional brain circuits that involves a persistent negativity bias.
Second, we discuss how effective treatments for MDD enhance mechanisms of neuroplasticity—including via serotonergic interventions—to restore synaptic, network, and behavioral function in ways that facilitate adaptive cognitive and emotional processing.
These treatments include typical monoaminergic antidepressants, novel antidepressants like ketamine and psychedelics, and psychotherapy and neuromodulation techniques.
At the end of the article, we discuss this framework from the perspective of effective science communication and provide useful language and metaphors for researchers, clinicians, and other professionals discussing MDD with a general or patient audience.
