How Does Ketamine Work for Treatment-Resistant Depression and Anxiety

A Different Approach to Treatment-Resistant Depression

For millions living with depression, anxiety, PTSD, or chronic pain, conventional treatments have fallen short. Ketamine — originally developed as an anesthetic — has emerged as one of the most significant advances in mental health treatment in decades.

At Discreet Ketamine, we use Ketamine Orally Disintegrating Tablets (ODT), a convenient and effective form that patients take at home under medical supervision.

What Is Ketamine ODT Treatment?

Ketamine ODT tablets dissolve sublingually (under the tongue), allowing direct absorption through the oral mucosa. Unlike IV ketamine requiring clinical settings, ODT tablets can be used at home with telehealth monitoring.

A typical session involves placing the tablet under the tongue for 10–15 minutes, with effects beginning within 15–20 minutes and lasting 45–90 minutes. A peer supervisor must be present throughout.

The Neuroscience: NMDA Receptors and Glutamate

Understanding ketamine requires understanding glutamate — the brain's primary excitatory neurotransmitter. While depression has traditionally been linked to serotonin deficiency, research increasingly points to the glutamate system as central to mood regulation.

Ketamine blocks NMDA receptors, triggering a cascade of downstream effects:

1. Glutamate surge — Blocking NMDA receptors on inhibitory interneurons temporarily increases glutamate release
2. AMPA receptor activation — Released glutamate activates AMPA receptors involved in synaptic transmission
3. BDNF release — AMPA activation stimulates Brain-Derived Neurotrophic Factor, essential for neuronal health
4. mTOR pathway activation — This signaling pathway promotes growth of new synaptic connections

This entire process unfolds within hours — not weeks — explaining ketamine's rapid antidepressant effects.

BDNF and Neuroplasticity: Rewiring the Brain

Ketamine's most compelling mechanism involves neuroplasticity — the brain's capacity to form new neural connections and reorganize existing ones.

Chronic depression, anxiety, and PTSD correlate with reduced synaptic density in the prefrontal cortex (decision-making, emotional regulation) and hippocampus (memory, learning). Cortisol and stress hormones damage these neural networks over time.

BDNF functions as fertilizer for the brain. By stimulating BDNF production, ketamine encourages growth and repair of weakened synapses. Animal studies demonstrate that a single ketamine dose can restore prefrontal cortex synaptic connections within 24 hours.

This neuroplastic effect distinguishes ketamine from virtually all other psychiatric medications — it actively promotes structural brain repair rather than merely adjusting neurotransmitter levels.

Breaking Negative Thought Loops

Beyond neurochemistry, ketamine creates a therapeutically valuable psychological state. Its dissociative properties help patients step outside entrenched negative thought patterns.

Treatment-resistant depression involves repetitive, self-critical thoughts that become neurologically reinforced over time. Ketamine temporarily loosens these rigid patterns, creating cognitive flexibility. During and after sessions, patients frequently report:

• Emotional relief and lightness
• New perspectives on longstanding problems
• Reduced intrusive thoughts
• Renewed engagement with life

This psychological opening is why integration — the process of translating session insights into lasting change — is so important.

What to Expect During a Session

A typical at-home session follows structured protocols:

How Ketamine Differs from Traditional Antidepressants

Traditional antidepressants (SSRIs, SNRIs, tricyclics, MAOIs) modulate serotonin, norepinephrine, or dopamine. While effective for many, they typically require 4–8 weeks and fail approximately 30–40% of depressed patients.

Ketamine operates through an entirely different pathway:

The Bottom Line

Ketamine treatment represents a fundamentally different approach to mental health. By targeting the glutamate system, stimulating BDNF, and promoting neuroplasticity, it addresses the structural brain changes associated with chronic depression, anxiety, and PTSD — not merely the symptoms.

For patients who have tried multiple medications without success, ketamine therapy offers a scientifically grounded path forward. Combined with therapeutic integration and ongoing medical support, it can help restore the brain's natural capacity for healing and growth.