Each month our editorial team sifts through hundreds of papers and curates notable findings—for practitioners and informed readers who want to stay current with the evidence. Subscribe to the monthly Research Digest for expert analysis and concise summaries of key papers.
In a small, carefully controlled study, seven people with major depression each received a single low-dose ketamine infusion on one day and a saline infusion on another day, without anyone knowing which was which. People who got ketamine showed clear improvement in their depressive symptoms within three days, while those…
In a small, controlled study of 18 people with treatment-resistant major depression, a single intravenous dose of the NMDA receptor antagonist ketamine (0.5 mg/kg) produced rapid drops in depression scores. Improvement began within about 2 hours and remained statistically significant compared with placebo for up to 1 week. The study…
Researchers tested a single intravenous dose of ketamine in 73 people with major depression that had not gotten better with usual treatments. In a two-site, double-blind trial, people were randomly given either ketamine or an active placebo (the anesthetic midazolam). Twenty-four hours after the infusion, people who got ketamine were…
Researchers tested a nasal spray form of esketamine together with a newly started oral antidepressant in adults whose depression had not improved after trying at least two antidepressants. Over four weeks, people who got esketamine plus a new antidepressant had faster and larger drops in depression symptoms than those who…
This phase 3, double-blind trial tested whether continuing esketamine nasal spray plus an oral antidepressant could delay relapse in adults with treatment-resistant depression who had already improved after an initial esketamine course. Of 297 patients who entered the randomized phase, continuing esketamine reduced relapse compared with switching to placebo nasal…
A group of international mood-disorder experts reviewed the research on ketamine and esketamine for adults whose depression did not get better with usual antidepressants. They found that these drugs work differently from standard antidepressants and can lift symptoms more quickly for some people with treatment-resistant depression. However, the experts also…
Adjunctive ketamine demonstrated a greater reduction in clinically significant suicidal ideation in depressed patients within 24 hours compared with midazolam, partially independently of antidepressant effect.
This paper is a careful review of research about treatment-resistant depression. The authors looked through medical studies to see how doctors define this kind of depression, what makes it hard to assess, and which treatments have been tried. They describe drug strategies like adding lithium or thyroid hormone, switching antidepressant…
Repeated ketamine infusions have cumulative and sustained antidepressant effects. Reductions in depressive symptoms were maintained among responders through once-weekly infusions. These findings provide novel data on efficacious administration strategies for ketamine in patients with treatment-resistant depression. Future studies should further expand on optimizing administration to better translate the use of…
Researchers ran a clinical trial that directly compared ketamine treatment with electroconvulsive therapy (ECT) in people whose major depression had not improved with other treatments and who did not have psychosis. The trial found that ketamine was “noninferior” to ECT, which means ketamine worked at least as well as ECT…
This systematic review looked at studies of ketamine for people whose depression did not respond to usual treatments (treatment-resistant depression, TRD). Across 24 papers with 416 patients, most studies found that ketamine can reduce depressive symptoms quickly — often within hours — and it was also reported to lower suicidal…
This meta-analysis combined 20 randomized clinical trials up to February 22, 2019, and found that a single dose of ketamine produced rapid antidepressant effects that were strongest at 24 hours and that these effects were still detectable up to 7 days. The analysis also found that repeated ketamine doses helped…
