What Does Research Suggest About Ketamine for Treatment-Resistant Depression?
Research suggests ketamine may help many adults whose depression has not improved with standard antidepressants, sometimes within hours to days. The benefit can fade without continued treatment, and long-term data are still limited. In one of the largest head-to-head trials to date, 55% of people treated with intravenous ketamine had a response after three weeks, compared with 41% of those treated with electroconvulsive therapy (ECT). That is encouraging, and it also means close to half did not respond. This post walks through what the studies found, what they have not answered yet, and what to ask before starting.
What have the major studies found?
Treatment-resistant depression (TRD) usually means depression that has not improved enough after at least two adequate antidepressant trials. About one in three people with depression fall into this group.
A 2025 meta-analysis comparing ketamine with ECT found no significant differences in response, remission or relapse, while its authors called for more studies to confirm that. A separate analysis of ELEKT-D found that outpatients with moderately severe or severe depression improved more with ketamine than with ECT, which may matter for people who want to avoid a hospital-based option.
How long do the effects last?
This is the question many people care about most, and the honest answer is that it varies. In the Mount Sinai repeated-infusion study, the median time to relapse among responders was 18 days after the last infusion. A consensus statement summarized by The Carlat Report noted relapse rates as high as nearly 90% within four weeks in some of the studies it reviewed.
Those numbers come from short courses of treatment with no planned follow-up care. In ELEKT-D, people who responded were followed for six months while receiving care chosen with their physicians, and in ESCAPE-TRD, esketamine was given on an ongoing schedule for 32 weeks. Research suggests that how a response is maintained matters as much as how it starts. A real-world meta-analysis also found that the benefit did not appear to shrink with repeated treatments, though people with more treatment failures reached remission less often.
What does the research not tell us yet?
Most ketamine articles stop at the good news. These gaps are worth naming plainly.
Adding therapy. A 2025 systematic review found insufficient evidence that ketamine-assisted psychotherapy works better than ketamine alone. Another review found symptom reductions with therapy, some lasting up to six months, but the studies varied widely in design.
Long-term safety. The same consensus statement noted a lack of long-term safety data, including questions about cognition and misuse.
Harder-to-treat depression. A 2026 analysis of two randomized trials (154 adults) found ketamine reduced depression scores over 15 days, including thoughts of suicide, but some symptoms, such as apparent sadness and inner tension, improved less in people with more treatment resistance.
Who benefits most. No clear rule yet predicts who will respond, which is why careful screening and honest expectations matter.
Is ketamine for depression approved and safe?
Two different medicines are in the conversation, and the difference matters. Esketamine (Spravato) is a nasal spray the FDA approved for treatment-resistant depression in 2019 alongside an oral antidepressant, and in January 2025 as a standalone treatment. It is given only in certified settings under a safety program. Intravenous ketamine is FDA-approved as an anesthetic and is used off-label for depression, which is common in medicine but means no FDA-reviewed label for this use.
Common effects during treatment include dissociation (a floating or detached feeling), nausea and dizziness. Blood pressure and heart rate usually rise for an hour or two, and in three trials summarized by The Carlat Report, about 30% of patients had a spike above 180/100 mmHg, which is why monitoring during sessions is standard. Repeated use has also been linked to urinary and bladder symptoms. Anyone with uncontrolled high blood pressure, psychosis or a substance-use history should discuss risks with a clinician first.
What should you ask a clinic before starting?
The research points to a few questions that reveal how careful a clinic is.
Who evaluates me first, and how do you decide whether I am a candidate?
How will you track whether it is working, for example with a standard depression scale?
What happens after the initial series if I respond? What if I do not?
How are blood pressure and other vital signs monitored during a session?
How does this fit with my current medications and my existing therapist or psychiatrist?
What do you tell patients about relapse and about the limits of the evidence?
A good clinic welcomes these questions. If you are ready to talk it through, Satori Health and Wellness in St. George is glad to answer them.
Frequently asked questions
Is ketamine as effective as ECT for treatment-resistant depression? In ELEKT-D, intravenous ketamine was noninferior to ECT in people without psychosis, and a 2025 meta-analysis found no significant difference. One Swedish inpatient trial favored ECT, so the evidence is not unanimous.
How quickly can ketamine work? Research suggests some people notice improvement within hours to a day or two of an infusion, and early response was linked to a better outcome in one study. Timing varies from person to person.
Does the benefit last? It can fade, sometimes within weeks, which is why follow-up planning matters. Studies of longer treatment courses and maintenance are still developing.
If you are in crisis right now, please call or text 988 (the Suicide and Crisis Lifeline) or contact local emergency services. You deserve support today, not only after research is done.
