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.
Research shows ketamine can lift low mood and depression faster than standard antidepressants for some people. Many clinical trials report rapid improvements, often within hours to a day, especially in people whose depression did not improve on usual medicines. However, effects after a single dose often fade over days to weeks, and scientists are still studying how to give ketamine safely over the long term. Scientists have good short-term evidence for ketamine and for a related nasal drug called esketamine. At the same time, researchers warn about common short-term side effects, unclear long-term risks, possible misuse, and gaps in understanding exactly how ketamine works in people. More large and longer studies are needed to answer these questions.
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…
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…
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…
Treatment-resistant depression means depression that does not get better after usual treatments. Scientists do not all agree on one clear definition, which makes it hard to know exactly how common it is or which treatments work best. Using the definition that regulators often use, about 30% of people with depression…
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…
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…
Researchers around the world have started clinical studies again to see if psychedelic drugs can help treat serious mental health problems. This work picks up after research that stopped around the 1950s. Scientists are running controlled studies to test whether these substances can safely reduce problems like depression, anxiety, addiction…
Researchers tested repeated subcutaneous (under-the-skin) injections of racemic ketamine in people whose depression had not improved after at least two antidepressant trials. People got injections twice a week for 4 weeks and neither participants nor the raters knew which drug they were getting. When the study allowed higher, response-guided ketamine…
This paper reported a small, randomized trial of 64 people with treatment-resistant major depression who were given a single intravenous dose of ketamine or a saline placebo. The authors said depression and suicidal thoughts dropped quickly — within an hour — and that benefits lasted up to two months, but…
This paper looks at studies that use transcranial magnetic stimulation and ketamine together to treat depression that has not improved with usual treatments. It notes that each method can reduce depressive symptoms on its own. Some recent research suggests that giving them together might make the benefits stronger and last…
