What ketamine treats, and how strong the evidence really is

Strong evidence

Treatment-resistant depression (TRD)

This is where the evidence is strongest. When two or more adequate antidepressant trials haven't worked, randomized trials of IV ketamine have repeatedly shown rapid reductions in depressive symptoms. These often come within 24 hours, where conventional antidepressants take weeks.

Esketamine's record is narrower than the marketing suggests. The pivotal four-week trial in Spravato®'s label added it to a newly started oral antidepressant. That combination beat the antidepressant alone by 4 points on the 60-point MADRS depression scale, and most of that difference was present within 24 hours. A separate four-week monotherapy trial beat placebo by 5 to 7 points and separated from placebo by day 2. Two other four-week trials did not reach statistical significance. One used fixed doses, and one enrolled patients 65 and older. Speed is the genuinely novel thing about ketamine. The catch is that effects fade without maintenance in many patients. And in a large 2023 trial, about 45% of patients did not respond after six infusions.

What those response rates mean in practice is covered in How Well Does Ketamine Work? If you are comparing the two forms, see Ketamine vs. Spravato and how insurance covers Spravato. If you are weighing other options after antidepressants have failed, see Ketamine vs. TMS, and if ketamine itself has not helped, see what comes next.

FDA-approved, with important limits

Depression with acute suicidal thinking

Spravato® (esketamine) is FDA-approved to treat depressive symptoms in adults with major depressive disorder who have acute suicidal thoughts or behavior. That approval is for use together with an oral antidepressant. Its label states that it has not been shown to prevent suicide or reduce suicidal thoughts or behavior. Nor does it replace hospitalization when hospitalization is needed. Separately, a 2026 meta-analysis of 26 randomized trials found that IV ketamine rapidly reduced suicidal symptoms in the short term. Longer-term outcomes are not well established. Ketamine is an addition to crisis care, never a substitute for it. If you are in immediate danger, call 911 or go to the nearest emergency room. If you are in crisis now, call or text 988.

Mixed evidence

Bipolar depression

Small trials suggest rapid effects similar to unipolar depression. But treatment requires extra caution around triggering mania. This belongs with a psychiatrist experienced in bipolar disorder, not a standalone infusion clinic.

Chronic pain syndromes

Ketamine has a long history in anesthesia and pain medicine. Higher-dose, longer infusions are used for conditions like CRPS and refractory neuropathic pain. Protocols differ substantially from psychiatric dosing. A mental-health clinic is not automatically equipped for pain protocols, or vice versa.

PTSD

Thinner than clinic websites suggest. A 2026 systematic review looked at seven randomized trials of IV ketamine for PTSD, with 323 participants in total. It found meaningful symptom improvement in only two of them. The largest trial randomized 158 veterans and service members to eight infusions of placebo, low-dose, or standard-dose ketamine. It found no benefit over placebo on either PTSD rating scale, though the standard dose did improve depression scores. Research into pairing ketamine with trauma-focused therapy is ongoing. The studies published so far are mostly small and low quality. For now, PTSD is an open research question.

Thin evidence: be skeptical of confident claims

Generalized anxiety, OCD, substance use disorders, eating disorders

Early studies exist for each, some encouraging. But when a clinic's website lists a dozen conditions with equal confidence, treat the list as advertising. For these conditions, ketamine is reasonably framed as experimental. It's worth discussing with your psychiatrist and worth entering a clinical trial for. But it's not something to buy a package for on the strength of a landing page.