For decades, depression treatment has centered around the monoamine hypothesis—the belief that low levels of serotonin, norepinephrine, and dopamine cause depressive symptoms. This framework has guided the development of most antidepressants, from SSRIs to SNRIs and beyond. While these medications have undoubtedly helped many individuals, they also have clear limitations. Even when effective, they often take weeks to show meaningful results, and even then, many clients report not feeling "happy" but simply "less sad"—a phenomenon known as emotional blunting.
If serotonin levels in the brain increase within hours of taking an SSRI, why does it take four to six weeks for symptoms to improve? Shouldn’t immediate biochemical changes lead to immediate emotional relief? This lag challenges the idea that serotonin deficiency alone explains depression. Furthermore, several studies have shown that individuals with low serotonin levels are not always depressed, and conversely, individuals with normal serotonin levels can still experience significant depressive symptoms. This suggests that serotonin imbalance is not a sufficient explanation for the complexity of depression and points toward the need for a broader understanding of its neurobiological underpinnings.
This is where glutamate comes in. Unlike serotonin and its cousins, glutamate is the brain's primary excitatory neurotransmitter, essential for synaptic plasticity—the brain’s ability to adapt, grow, and reorganize. When we target glutamate signaling, we aren't just flooding the synaptic cleft with a neurotransmitter and waiting. Instead, we are promoting actual brain remodeling, leading to rapid and profound changes in mood.
When treatments like Spravato (esketamine) and now Auvelity (dextromethorphan-bupropion) act on glutamate systems, improvements in mood can be seen within hours to days—not weeks. The contrast is stark: immediate neurochemical changes lead to immediate clinical results.
This rapid effect raises an important question: are our clients truly "depressed" in the way we’ve historically understood it, or are they suffering from a broader dysfunction of brain plasticity and emotional regulation? Maybe many are not "sad" in the traditional sense, but instead emotionally blunted—stuck in a neurological rigidity that monoamines cannot adequately address.
Among emerging treatments, Auvelity stands out. It uniquely combines dextromethorphan, an NMDA receptor antagonist (glutamate modulator), with bupropion, a norepinephrine-dopamine reuptake inhibitor. This dual mechanism not only enhances glutamatergic transmission but also boosts mood-related monoamines.
Clinical trials have shown that Auvelity has a superior effect size compared to traditional antidepressants. Effect size, simply put, measures the magnitude of a treatment’s impact. While statistical significance (the p-value) tells us whether a treatment likely works, effect size tells us how much it works. An antidepressant might be statistically better than placebo but only by a small margin. Auvelity, however, demonstrated a moderate to large effect size in clinical trials, meaning the degree of symptom reduction was clinically meaningful, not just statistically significant.
For clients, this means they are more likely to feel a profound, noticeable difference—not just a "maybe I’m a little better" experience, but "I feel like myself again."
Underlying Auvelity’s rapid benefits is its potential to promote neuroplasticity. By enhancing glutamate signaling, Auvelity may help restore synaptic connections damaged by chronic stress and depression. This is more than symptom relief; it’s neurological repair.
We’ve seen the power of neuroplasticity in studies like Eleanor Maguire’s research on London taxi drivers, where intensive learning actually reshaped brain structures. If learning can rewire the brain, then targeted treatments can too. Glutamate modulation opens the door to not just treating symptoms, but truly healing.
Maybe our traditional view of depression has been too narrow. Maybe it’s not just a "chemical imbalance" of serotonin, but a broader failure of the brain to adapt and regulate emotion. And maybe the path to healing isn't found in endlessly boosting monoamines, but in restoring the brain's natural plasticity.
Treatments like Auvelity, by targeting glutamate and enhancing neuroplasticity, represent a promising future—one where symptom relief is not delayed, not partial, but rapid and meaningful.
It’s time to stop settling for "less sad." Our clients deserve to feel truly alive again.
At South Chesapeake Psychiatry, we are true believers in science. Our commitment to our five pillars—Quality, Expertise, Excellence, Accountability, and Availability—means that we are always at the forefront of new treatment options, offering only the best to our clients. We take pride in being a practice that values innovation, accessibility, and real outcomes.
As one of our recent clients shared:
"South Chesapeake Psychiatry, I can’t say enough great things about South Chesapeake Psychiatry and Justin Ray. I was recently struggling with acute depression, and during a single phone appointment, I explained to Justin what I was going through. He prescribed a new, fast-acting medication for depression called Auvelity. Within just two days, I began to notice a real improvement. Now, about six days later, I’m feeling significantly better—not perfect, but tremendously improved.
What really stood out to me was the level of accessibility and care. After my initial consultation, I was able to follow up with Justin via email—something that’s very rare with other mental health professionals. Being able to consult with him by phone saved me nearly an hour of driving. It was incredibly convenient and made the whole experience much less stressful.
Justin and his staff have truly been a lifeline. I’m incredibly grateful for their support and care."
This is the standard we set—and the standard you deserve.
Schedule an appointment today to get diagnosed, receive a prescription, and continue your journey towards mental peace.
