Ketamine for Depression: Does It Work and Is It Safe?
20 Oct 2026
For depression that has not improved after several treatments, ketamine given under medical supervision has solid trial evidence behind it. In a major US trial it was non-inferior to electroconvulsive therapy (ECT) [1], and a meta-analysis of 49 trials found clear short-term benefit [2]. It is not a first-line treatment, the effect can fade, and it carries real risks, especially outside a monitored clinic [4].
Ketamine for Depression at a glance
- Versus ECT: 55.4% of people given ketamine responded, against 41.2% on ECT, in a 403-person trial [1].
- Versus another add-on medicine: esketamine nasal spray led to remission at week 8 in 27.1%, against 17.6% on quetiapine [3].
- Pooled evidence: 49 trials with 3,299 participants showed moderate to large early benefit [2].
- New review (October 2026): ketamine is used for treatment-resistant depression and pain, with safety, monitoring and telehealth prescribing flagged as challenges [4].
Who is ketamine meant for?
Ketamine is used for treatment-resistant depression. That usually means depression that has not improved after trials of at least two antidepressants at adequate doses. It is not meant for a first episode or for mild low mood. A new systematic review of 106 articles confirms that its mainstream uses are anaesthesia, treatment-resistant depression and pain, with other psychiatric uses still off-label [4].
What does the evidence say about ketamine for depression?
The strongest trial is ELEKT-D. In 403 adults with treatment-resistant depression who did not have psychosis, intravenous ketamine given twice a week for three weeks was compared with ECT three times a week [1]. Response, defined as at least a 50% fall in symptom score, was 55.4% with ketamine and 41.2% with ECT, which met the study's test for non-inferiority [1]. ECT was linked to a drop in memory recall that gradually recovered. Ketamine was linked to dissociation, a feeling of being detached from yourself or your surroundings [1].
Another trial, ESCAPE-TRD, compared esketamine nasal spray with quetiapine, each added to an existing antidepressant, in 676 people. Remission at week 8 was 27.1% with esketamine against 17.6% with quetiapine [3]. Funding came from the manufacturer of esketamine [3].
| Study | Comparison | Main finding |
|---|---|---|
| ELEKT-D, 403 adults | IV ketamine vs ECT | Response 55.4% vs 41.2%, ketamine non-inferior [1] |
| Meta-analysis, 49 trials | Ketamine formulations vs control | Moderate to large effect after first dose [2] |
| ESCAPE-TRD, 676 adults | Esketamine spray vs quetiapine | Remission at week 8: 27.1% vs 17.6% [3] |
What the main studies found [1,2,3].
How long do the benefits last?
This is the weak point. In the meta-analysis, racemic ketamine kept a significant effect during repeated dosing and at follow-up after the last dose. Esketamine did not reach significance at follow-up [2]. Higher doses worked better than low doses, but results varied a lot between trials [2]. In practice, a course of treatment is usually followed by a plan for maintenance, which is why ketamine works best as part of a wider programme and not on its own.
What are the risks and side effects?
Short-term effects include dissociation, dizziness and changes in perception, which is why sessions are done where staff can monitor you [1]. Ketamine is also misused recreationally, and a new review highlights recreational use, safety, monitoring and the growth of telehealth prescribing of oral and sublingual forms as unresolved challenges [4]. Take-home ketamine with little supervision is where many of the concerns lie.
Ketamine is not suitable for everyone. Your psychiatrist will want to know about heart conditions, blood pressure, a history of psychosis, and any substance use before suggesting it.
Where does ketamine fit with other treatments?
Ketamine sits alongside talking therapy, medicines and brain stimulation such as rTMS, not above them. For many people with depression, a sound first step is a complete assessment, a properly dosed antidepressant, and a structured therapy such as CBT. Ketamine becomes an option once those have not worked, or when symptoms are severe enough that a faster-acting option makes sense.
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What are the limits of the research?
Most ketamine trials are short and many are small. ELEKT-D was open-label, meaning patients and doctors knew which treatment was given [1]. The new October 2026 review is a broad overview, not a new trial, and it points to gaps in long-term data [4].
Getting help in Delhi
At Brain Bridge Clinic in Safdarjung Enclave, New Delhi, ketamine-assisted therapy is offered as medically administered, sub-anaesthetic dosing in a monitored clinical setting, together with structured psychotherapy, and only for treatment-resistant depression. Before that, an assessment reviews your diagnosis, past treatments, medical history and any substance use. Other options such as rTMS and CBT are discussed too. You can book an assessment to see whether ketamine is appropriate for you or whether another step comes first.
Related pages: Depression Anxiety, Ketamine Assisted Therapy, rTMS.
Frequently asked questions
Is ketamine approved for depression in India?
Rules differ by formulation and use, so ask your psychiatrist about the legal status of the specific product they propose. This article does not cover regulatory approvals.
Is ketamine better than ECT?
In one large trial it was non-inferior to ECT for response, with less memory impact but more dissociation [1]. It does not mean ketamine is right for everyone.
How quickly does ketamine work?
In the meta-analysis, effects were moderate to large right after the first dose [2]. Whether they last depends on repeat treatment and wider care.
Is ketamine safe?
Under supervision, short-term effects are mainly dissociation and dizziness [1]. Unsupervised or recreational use carries greater risks [4].
Can I take ketamine at home?
Reviews raise concerns about monitoring and telehealth prescribing of home formulations [4]. Discuss this with a psychiatrist before using it.
References
- Anand A, Mathew SJ, Sanacora G, et al. Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. The New England journal of medicine. 2023;388(25):2315-2325. doi:10.1056/NEJMoa2302399. PMID 37224232.
- Nikolin S, Rodgers A, Schwaab A, et al. Ketamine for the treatment of major depression: a systematic review and meta-analysis. EClinicalMedicine. 2023;62:102127. doi:10.1016/j.eclinm.2023.102127. PMID 37593223.
- Reif A, Bitter I, Buyze J, et al. Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression. The New England journal of medicine. 2023;389(14):1298-1309. doi:10.1056/NEJMoa2304145. PMID 37792613.
- Kinney MM, Bowers ZL. Ketamine in psychiatry: a systematic review of clinical applications, safety considerations, and emerging challenges. Frontiers in psychiatry. 2026;17:1949261. doi:10.3389/fpsyt.2026.1949261. PMID 42889292.