Ketamine has an unusual reputation. It can ease depressive symptoms faster than the usual antidepressants, but in most studies the effect is short-lived, and many of the trials are small. This article explains what the trials found, where they fall short, and why we treat it as a specialized option rather than a routine one.
IV ketamine: fast, and often short-lived
In a systematic review and individual participant data meta-analysis, a single intravenous dose reduced suicidal ideation within one day in 167 people across 10 controlled trials. The benefit was still measurable for up to a week. The authors found that the anti-suicidal effect was only partly explained by improvements in overall depression severity (Wilkinson 2017).
The same authors judged the evidence preliminary. Follow-up was short, with no data beyond seven days. These are trials of a single dose given in a clinic, not a long-term treatment plan.
Esketamine: the approved version
Esketamine, the S-enantiomer of ketamine, is sold as a nasal spray (Spravato). The FDA approved it in March 2019 for treatment-resistant depression, to be used together with an oral antidepressant. It can be taken only under the supervision of a health care professional in a certified office (PsychNews 2019).
That approval covers the nasal spray only. It does not make compounded oral ketamine an approved treatment.
Oral ketamine: a small and uneven evidence base
Oral ketamine is not approved for depression, and there is no commercial oral formulation, so it is compounded from the injectable form. In a randomized trial of 41 outpatients who had not responded to at least two antidepressants, 6 of 22 people taking ketamine 1 mg/kg by mouth three times a week (27.3%) reached remission at day 21, versus none of 19 on placebo, and depression scores fell 12.75 points versus 2.49 (Domany 2019).
A review of the oral trials found that most were small and short, the longest lasting six weeks, and that the trials had difficulty masking the drug from participants. Pooled across the randomized trials, response and remission were only marginally better than placebo (Nuñez 2020, as summarized by the UIC review).
What the trials do not show
- How long the benefit lasts after treatment stops, because most trials followed patients for weeks, not months.
- Whether repeated treatment is safe over years. Heavy recreational use of ketamine is linked to bladder damage, and symptoms rise with dose and frequency (Anderson 2022).
- Whether oral ketamine works as well as the approved nasal spray or IV infusion, since the trials used different doses and routes.
- Whether it works for people with psychosis, substance use disorder, cardiovascular or thyroid disease, because most trials excluded them (UIC review).
Safety, in brief
Ketamine can cause dissociation, dizziness and sleepiness, and it can raise blood pressure. The UK patient leaflet for Spravato warns of a temporary blood pressure increase that may lead to serious complications in people with certain heart or brain conditions, and it advises not to drive or operate machinery until the next day after a restful sleep (Spravato leaflet). The companion article covers the details.
Where ketamine fits
Psychological treatments are the first treatments for depression, and medicines are also effective (WHO). Ketamine is not a replacement for therapy, a diagnosis or crisis care. If you are thinking about harming yourself, call or text 988 in the US, or call 911 if you are in danger right now.
What we do and do not do
We offer oral ketamine only after a physician review, as a specialized option for depression that has not responded to standard treatment. We explain the evidence in the terms above and follow up while you take it.
We do not promise a cure, we do not sell it as a shortcut, and we do not treat it as a substitute for therapy or emergency care.
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- 1.Wilkinson ST, Ballard ED, Bloch MH, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. Am J Psychiatry, 2018
- 2.Domany Y et al. Repeated oral ketamine for out-patient treatment of resistant depression: randomised, double-blind, placebo-controlled, proof-of-concept study. Br J Psychiatry, 2019
- 3.What evidence is available for oral ketamine in treatment-resistant major depressive disorder? UIC College of Pharmacy, 2022
- 4.Spravato (esketamine) patient information leaflet Electronic Medicines Compendium (UK)
- 5.FDA approves fast-acting esketamine for treatment-resistant depression PsychNews alert, March 2019
- 6.Ketamine-induced cystitis: a comprehensive review of the urologic effects of this psychoactive drug. Anderson DJ et al. Health Psychology Research, 2022
- 7.Depression fact sheet World Health Organization, 2026