Ketamine treatment has helped fill in the details that the serotonin model of depression missed

The Serotonin model of depression missed a lot, and ketamine treatment for depression helped fill in some of the gaps

Introduction

For decades, depression was primarily explained through the serotonin model—the belief that a chemical imbalance in serotonin caused depressive symptoms. While that theory led to important advancements, it left many patients without meaningful relief. At Axis Integrated Mental Health, we’ve seen firsthand that depression is more complex and that ketamine offers a new path forward. This blog explores how ketamine works differently from traditional antidepressants and why it’s such a powerful tool for treatment-resistant depression.

How Ketamine Treatment Goes Beyond the Serotonin Model of Depression

The serotonin model—the belief that depression stems from a serotonin deficiency, a key neurotransmitter in the brain—led to the development of SSRIs and other medications. But it no longer explains the full picture. At Axis Integrated Mental Health, we now know depression is more complex, involving multiple brain systems, networks, and neurochemicals. Ketamine treatment has opened a new chapter in our understanding of depression’s root causes—and how we can treat it.

The Science of Depression: More Than Just Serotonin

The serotonin hypothesis, developed in the 1960s, suggested that low serotonin levels caused depression. While helpful at the time, this monoamine model is now outdated. Research has shown that depression isn’t just about one chemical. Other neurotransmitters, such as dopamine and norepinephrine, are also involved. More recently, scientists have identified the importance of brain networks, inflammatory markers, and glutamate, a different neurotransmitter that plays a major role in mood regulation and brain health.

How Ketamine Works in the Brain

Ketamine doesn’t work like traditional antidepressants. Instead of focusing on serotonin, it targets the NMDA receptor, which interacts with glutamate. When ketamine blocks these receptors, it triggers a cascade of effects that ultimately boost brain-derived neurotrophic factor (BDNF). This protein encourages brain cells to grow and form new connections. This process is known as neuroplasticity.

By increasing neuroplasticity, ketamine helps the brain form new, healthier communication pathways between networks that are often disrupted in depression. These changes can begin within hours of treatment.

BDNF and Neuroplasticity: Why Ketamine Works Fast

Unlike SSRIs, which can take 4-6 weeks to begin working, ketamine’s antidepressant effects are often felt within 24-48 hours. That’s because it activates BDNF and enhances the brain’s ability to rewire itself. This is especially important for individuals with treatment-resistant depression who have not responded to multiple other medications.

Breaking the Loop: Trauma, Depression, and Brain Networks

Many patients struggling with depression have a history of trauma. When the brain perceives danger, it forms fast, energy-efficient pathways to remember and react to threats. Over time, these patterns can become automatic, leading to chronic negative thought loops. This is where ketamine shines.

By disrupting the overactive Default Mode Network (DMN) and encouraging new network connections, ketamine allows the brain to let go of unhelpful shortcuts and build healthier cognitive pathways. This is particularly impactful for patients with PTSD, anxiety, and recurring intrusive thoughts.

Ketamine’s Impact on PTSD, Anxiety, and Suicidal Thoughts

At Axis, we see that ketamine isn’t just effective for depression—it also helps patients living with anxiety, PTSD, and suicidal ideation. Studies show that ketamine rapidly reduces suicidal thoughts and emotional distress. In our clinic, patients often report feeling calm, present, and detached from traumatic memories after treatment, which helps them begin the healing process.

IV vs. Nasal Ketamine: What’s the Difference?

Ketamine can be administered in several forms. The most common are intravenous (IV) infusions and esketamine nasal spray (Spravato). IV ketamine allows for precise dosing and has been used in research settings for years. Spravato, approved by the FDA in 2019, must be administered under clinical supervision and offers a more accessible option for some patients. At Axis, we help determine which method is best based on your needs and medical history.

Is Ketamine Right for You?

Ketamine isn’t for everyone. It is typically recommended for individuals with treatment-resistant depression or those struggling with severe symptoms despite trying multiple medications. It's not considered a first-line treatment. Our providers conduct a thorough evaluation to ensure ketamine is a safe and appropriate option.

Real Healing, Real People: What We’ve Seen at Axis

Our clinic in Aurora, just outside Denver, has helped hundreds of patients find relief through ketamine treatment. We’ve seen dramatic improvements in individuals who have spent years feeling hopeless. These transformations reinforce our belief in ketamine’s potential to restore not just brain function, but lives.

Start Your Journey: How to Begin Ketamine Treatment at Axis

If you’re curious about ketamine treatment for depression, anxiety, or PTSD, our team is here to guide you. Schedule a consultation at Axis Integrated Mental Health and discover whether ketamine therapy is right for your healing path. We combine cutting-edge science with compassionate care to give you the best chance at lasting recovery. Please reach out to us at (720) 400-7025 if you have any questions!

Conclusion

While the serotonin model served as a starting point in understanding depression, today’s science points us in a new direction. Ketamine doesn’t just mask symptoms—it helps the brain reconnect, rewire, and rebuild. At Axis Integrated Mental Health, we’re proud to offer a treatment that brings fast relief, supports healing from trauma, and gives hope to those who’ve tried everything else. If you’re ready to explore what’s next in your journey, we’re here to walk with you.

More information:

https://www.nature.com/articles/s41380-022-01661-0

https://www.yalemedicine.org/news/ketamine-depression

https://www.sciencedirect.com/science/article/pii/S2213158218301839

https://my.clevelandclinic.org/health/articles/22839-glutamate

FAQs

1. How is ketamine different from traditional antidepressants like SSRIs?
2. What is the serotonin model of depression, and why is it outdated?
3. How does ketamine create neuroplasticity in the brain?
4. Is ketamine safe for long-term use or repeat treatment?
5. Can ketamine help with trauma, PTSD, or suicidal thoughts?