Does Ketamine Therapy Work? An Honest Look at the Evidence

For some people, in the short term, the research says it can. Randomized trials and systematic reviews have found that ketamine can reduce depressive symptoms more than a comparison treatment within about a day. Whether that improvement lasts, and who is most likely to benefit, is much less certain, and a large share of trial participants did not respond.

Treat what follows as a summary of research, not a forecast for you. The figures come from studies with their own doses, routes, and participants, most of whom received ketamine through a vein, and none of them are results from our clinic.

That ketamine may help in the short term, with real uncertainty attached. A 2021 Cochrane review, which included 31 ketamine trials in unipolar depression, found that ketamine may increase response and remission compared with placebo at 24 hours. It rated that evidence as very low certainty and said it is not entirely clear how the findings translate into clinical practice.

A 2020 meta-analysis of 20 randomized trials painted a similar picture. The largest difference from control treatments appeared 24 hours after a single dose and stayed measurable for up to about a week, while repeated doses helped hold on to the early improvement during a course of treatment.

Individual trials show both the promise and the limits:

They are thresholds on a standard depression rating scale. Response usually means a person's score fell by at least half from where it started. Remission means the score dropped below a low cutoff, which in the KADS trial was 10 or under on the Montgomery-Åsberg Depression Rating Scale.

Both are measured at a fixed point, such as 24 hours or four weeks. Someone can meet the response threshold one week and lose it the next, which is why how long the benefit lasts is a separate question from whether it appears at all. Read the other way, the same trials show that many participants, and in some cases most, did not respond or reach remission.

Many trials enrolled adults whose depression had not improved enough with at least two antidepressants. KADS, for example, enrolled adults 18 and older with major depression lasting at least three months, an insufficient response to two or more adequate antidepressant trials, and a minimum symptom score.

Of the 64 studies in the 2021 Cochrane review, which covered ketamine and related drugs, 19 recruited only people with treatment-resistant depression. One dosing trial enrolled adults aged 18 to 64, and a small study focused on adults 60 and older. Findings from these groups may not carry over to people with other conditions or health histories, which is one reason an evaluation comes before any treatment.

They are significant, and any honest account of ketamine therapy has to include them:

It means going in with realistic expectations. Ketamine therapy may help, may help only for a while, or may not help at all, and a careful provider will tell you so plainly. At our clinic, the supervising clinician calculates each dose for you, typical plans involve a series of sessions over several weeks, and the plan is then reassessed so it can continue, be spaced out, or stop depending on your response. With your permission, we also work alongside the clinicians you already see.