Ketamine Therapy for Depression: What to Know When Traditional Treatment Hasn’t Been Enough

Ketamine therapy for depression can sound like a big next step, especially when you’ve already spent months or years trying medications, therapy, lifestyle changes, or some combination of all three. But for people who feel like they’ve tried everything and are still struggling, ketamine has opened a new and genuinely promising door.

Depression is not simply feeling sad or having a hard week. Major depressive disorder is a recognized mental health condition in the DSM-5-TR, and it can affect sleep, energy, motivation, concentration, relationships, and your ability to function in everyday life.[1]

And sometimes, our traditional treatments simply don’t provide enough relief. That is where treatments like intravenous ketamine, particularly when thoughtfully paired with psychotherapy, may be worth exploring.

Table of Contents

• What is ketamine therapy for depression?
• How ketamine works differently for depression
• Ketamine-assisted therapy and psychotherapy
• What happens during a ketamine infusion?
• Who may benefit from ketamine treatment?
• Does ketamine therapy for depression really work?
• Taking the next step with ketamine therapy

What Is Ketamine Therapy for Depression?

Ketamine has been used medically as an anesthetic for decades. More recently, researchers discovered that lower doses of IV ketamine can have rapid antidepressant effects, particularly for people with treatment-resistant depression.[2]

When ketamine is administered intravenously for depression, it is considered an off-label treatment. This means ketamine itself is FDA-approved as an anesthetic, but IV ketamine has not been FDA-approved specifically for psychiatric conditions.[3]

This is different from esketamine, sold under the brand name Spravato, which is a related medication administered as a nasal spray and is FDA-approved for certain forms of depression.[3]

In a ketamine-assisted therapy model, the medication is not necessarily viewed as the entire treatment. Instead, ketamine is combined with intentional therapeutic work before and after the infusion.

How Ketamine Infusions May Help Treatment-Resistant Depression

Most traditional antidepressants influence neurotransmitter systems such as serotonin or norepinephrine. Ketamine works differently, primarily interacting with the brain’s glutamate system and NMDA receptors.

Researchers believe these effects may temporarily influence neuroplasticity, or the brain’s ability to form and reorganize neural connections.[4]

That matters because depression can sometimes feel incredibly rigid.

Thoughts like:

• “Nothing is ever going to change.”
• “I’ve already tried everything.”
• “I’m always going to feel this way.”
• “I know what my therapist is saying, but I can’t feel it.”

can become deeply ingrained.

Ketamine may create a period in which some people experience greater psychological flexibility. The antidepressant effects can also occur surprisingly quickly, sometimes within hours or days rather than the weeks typically associated with conventional antidepressants.[2]

Ketamine-Assisted Therapy: Where Psychotherapy Fits

This is the part of ketamine therapy for depression that I find especially interesting as a therapist.

The goal isn’t simply, “Here is ketamine. Hopefully you feel better.”

Ketamine-assisted psychotherapy may include:

• Preparing emotionally for the experience
• Identifying intentions before an infusion
• Therapeutic support surrounding treatment
• Processing thoughts, emotions, or memories afterward
• Integrating new insights into everyday life

Think about it this way: ketamine may help create an opening, but therapy helps us explore what we want to do with that opening.

Research into this combination is still developing. A 2026 systematic review found that ketamine-assisted psychotherapy was associated with improvements in depression across the studies reviewed, but controlled studies have not yet demonstrated clearly that adding psychotherapy produces greater antidepressant effects than comparison treatments.[5]

So I don’t want to oversell this. We have good evidence for ketamine’s antidepressant effects, and promising reasons to integrate therapy thoughtfully, but we still need more high-quality research specifically examining the combination.

If traditional depression treatment hasn’t brought the relief you hoped for, contact us to learn whether ketamine-assisted therapy could be an appropriate next step for you.

What Happens During a Ketamine Infusion?

Ketamine treatment should take place in an appropriately supervised medical setting.

During an IV ketamine infusion, medication is administered while your medical team monitors you. People may temporarily experience:

• Changes in perception
• A sense of distance from their body or surroundings
• Dizziness or lightheadedness
• Nausea
• Sleepiness
• Changes in blood pressure
• Dissociative sensations

These side effects of ketamine usually occur during or shortly after treatment and are one reason medical screening and monitoring matter.[6]

The experience itself varies enormously. Some people have profound emotional insights. Others simply feel relaxed, detached, or introspective.

There is no “right” ketamine experience you are supposed to have.

Who May Benefit From Ketamine Treatment for Depression?

Ketamine has been studied most extensively in people with treatment-resistant depression, meaning depression that has not adequately improved after appropriate treatment attempts.[6]

That does not mean ketamine should automatically be the next treatment for everyone who is depressed.

A qualified provider should evaluate your psychiatric history, current medications, physical health, treatment history, substance use history, and other factors before determining whether ketamine is appropriate.

Depression is complicated. Sometimes finding effective treatment requires more than one approach.

If you feel like you’ve been doing all the “right” things and are still struggling, we can help you explore whether another treatment option belongs in your plan.

Does Ketamine Therapy for Depression Really Work?

There is legitimate reason for optimism.

A large systematic review and meta-analysis examining 49 randomized controlled trials found meaningful antidepressant effects following ketamine treatment.[2] Another real-world review involving 79 studies estimated that approximately 45% of patients responded to ketamine treatment and about 30% achieved remission, although responses varied significantly from person to person.[7]

The bigger question is often how long those improvements last.

For some people, the effect of a single infusion can fade, which is why treatment frequently involves a series of infusions and, for some patients, ongoing maintenance. Research into the best long-term protocols continues.[6]

Ketamine isn’t a magic reset button.

But for someone who has spent years feeling trapped inside depression, even creating enough relief to engage more deeply in therapy, relationships, movement, connection, or everyday life can be incredibly meaningful.

Ketamine Therapy for Depression: Finding a Different Way Forward

If depression has convinced you that nothing will ever change, I want you to know that there may still be treatments you haven’t explored.

Ketamine therapy for depression offers a different approach, particularly for people who haven’t found enough relief through traditional treatment. And when medication is paired intentionally with thoughtful therapeutic support, the goal isn’t simply to reduce symptoms. It’s to help you take whatever opening appears and turn it into meaningful, lasting change.

You don’t have to figure out whether ketamine is right for you on your own. If you’re ready to explore your options, contact us today to take the next step toward healing.

Sources

[1] American Psychiatric Association. About DSM-5-TR and information on depressive disorders.
American Psychiatric Association: About DSM-5-TR 

[2] Walsh Z, et al. Ketamine for the treatment of major depression: a systematic review and meta-analysis. Analysis included 49 randomized controlled trials and 3,299 participants.
View the study on PubMed 

[3] U.S. Food and Drug Administration. Information regarding ketamine’s approved uses and the distinction between ketamine and FDA-approved esketamine.
FDA information on ketamine use 

[4] Joneborg I, et al. Active mechanisms of ketamine-assisted psychotherapy: A systematic review. Journal of Affective Disorders. 2022.
View the systematic review on PubMed

[5] Simpson RJ, Juruena MF. Effectiveness of ketamine-assisted psychotherapy as a treatment for treatment-resistant depression: a systematic review. Psychopharmacology. 2026.
View the 2026 review on PubMed 

[6] Swainson J, et al. The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder. Canadian Journal of Psychiatry.
View the CANMAT recommendations on PubMed 

[7] Nikolin S, et al. Real-world effectiveness of ketamine in treatment-resistant depression: A systematic review and meta-analysis. Journal of Affective Disorders. 2022.
View the real-world meta-analysis on PubMed