Ketamine Infusions for Depression: What the Latest Research Actually Shows

Ketamine Infusions for Depression: What the Latest Research Actually Shows.

A plain-language look at where the science stands in 2026 — for anyone weighing ketamine therapy for depression that hasn’t responded to other treatments.

If you’ve tried two or more antidepressants and still feel stuck, you’re not alone — and you’re not out of options. Roughly a third of people with depression don’t get meaningful relief from standard medications, a pattern clinicians call treatment-resistant depression (TRD). Over the past few years, ketamine infusion therapy has moved from a promising experiment to one of the best-studied rapid-acting treatments for exactly this situation. Here’s what the research shows.

What ketamine infusion therapy is

Ketamine is an anesthetic that has been used safely in hospitals for decades. At much lower (“subanesthetic”) doses given slowly through an IV, it works very differently from traditional antidepressants. Instead of adjusting serotonin over weeks, ketamine acts on the brain’s glutamate system — the chemistry behind learning and forming new connections between brain cells. That’s the leading explanation for why some people feel a shift within hours to days rather than months.

It ranks among the most effective options for hard-to-treat depression

When researchers pool many clinical trials together, ketamine consistently lands near the top of the list. A 2024 network meta-analysis of 69 randomized trials found that only a handful of treatments clearly outperformed placebo for treatment-resistant depression — and ketamine was one of them, alongside ECT, transcranial magnetic stimulation, and a small number of others. A separate 2024 analysis of 72 trials reached a similar conclusion, ranking ketamine among the preferred options for its balance of effectiveness and tolerability. (That same review counted the related nasal-spray medicine esketamine among the top choices too, though it was somewhat less well tolerated.)

As effective as ECT for many people — with fewer memory complaints

Electroconvulsive therapy (ECT) has long been considered the most powerful treatment for severe depression, but it requires anesthesia and can affect memory. In a large 2023 head-to-head trial published in the New England Journal of Medicine (the ELEKT-D study, 403 patients), IV ketamine was at least as effective as ECT for non-psychotic treatment-resistant depression — and patients on ketamine reported fewer memory problems at three weeks. A 2025 review that combined six comparison studies came to the same bottom line: ketamine was not inferior to ECT, with a similar rate of side effects.

Relief can come quickly

One of the most striking features of ketamine is speed. Where traditional antidepressants often take four to eight weeks to work, ketamine’s effects can begin within a day or two. That rapid onset is part of why it has drawn so much interest for people who are struggling right now, including those with intense hopelessness or suicidal thoughts. The trade-off is that a single dose doesn’t last forever, which is why treatment is usually given as a short series of infusions and then maintained over time.

A milestone in 2025

In January 2025, the FDA approved esketamine (Spravato) — a nasal-spray cousin of IV ketamine derived from the same molecule — as a stand-alone treatment for treatment-resistant depression, the first time any TRD medication had been cleared to be used on its own rather than added to another antidepressant. It’s a sign of how far this class of rapid-acting treatments has come, and how seriously the field now takes it.

Not just depression

Depression is where the evidence is strongest, but researchers are also studying ketamine for related conditions. Early trials suggest possible benefit for post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD), and some programs pair ketamine with therapy to help people process what comes up during and after sessions. This research is younger and less settled than the depression data, so it’s best thought of as promising rather than proven.

The bottom line

For depression that hasn’t responded to other treatments, ketamine infusion therapy is one of the most evidence-supported rapid-acting options available today — comparable to ECT for many people, faster than standard antidepressants, and generally well tolerated when delivered under proper medical supervision. It isn’t a cure, and it isn’t right for everyone, but for the right person it can open a door that felt closed.

Curious whether ketamine therapy might be a fit for you? Refound Center offers clinician-led ketamine infusion therapy in the North Denver to Fort Collins area. Reach out to schedule a consultation and we’ll walk through your history and options together.

Medical disclaimer

This article is for general educational purposes only and is not medical advice, diagnosis, or treatment. Ketamine therapy is not appropriate for everyone. Talk with a qualified clinician about your individual history, medications, and goals before starting any treatment. If you are in crisis or thinking about harming yourself, call or text 988 (the Suicide & Crisis Lifeline) in the U.S.

Sources & further reading (studies identified via PubMed):

Saelens J, et al. Relative effectiveness of antidepressant treatments in treatment-resistant depression: a systematic review and network meta-analysis. Neuropsychopharmacology, 2024. https://doi.org/10.1038/s41386-024-02044-5

Guo Q, et al. Efficacy and safety of eight enhanced therapies for treatment-resistant depression: a network meta-analysis of RCTs. Psychiatry Research, 2024. https://doi.org/10.1016/j.psychres.2024.116018

Anand A, et al. Ketamine versus ECT for nonpsychotic treatment-resistant major depression (ELEKT-D). New England Journal of Medicine, 2023. https://doi.org/10.1056/NEJMoa2302399

Song G, Ugwah-Oguejiofor UC. Ketamine compared to ECT for treatment-resistant depression: a systematic review and meta-analysis. Int J Psychiatry Clin Pract, 2025. https://doi.org/10.1080/13651501.2025.2576205

Johnson & Johnson / FDA. Spravato (esketamine) approved as the first monotherapy for treatment-resistant depression, January 21, 2025. https://www.jnj.com/media-center/press-releases/spravato-esketamine-approved-in-the-u-s-as-the-first-and-only-monotherapy-for-adults-with-treatment-resistant-depression