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 several different ways can help with sadness or low mood. Right now, the strongest clinical evidence for a fast-acting drug comes from ketamine and its approved form esketamine. At the same time, a wave of studies on classic psychedelics (psilocybin, LSD, DMT) and entactogens (MDMA) looks promising, especially when the drug is given together with careful psychological support. However, most psychedelic studies are still small or early-stage. They often rely on the setting, preparation, and therapy as part of the treatment, so researchers say we need larger, controlled trials and more long-term safety data. Also, non-drug options like brain stimulation and standard psychotherapies remain important parts of treatment plans and have mixed but useful evidence.
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…
The CANMAT 2023 update gives doctors clear, up-to-date advice for treating adults with major depressive disorder. It puts evidence into a practical, clinician-friendly format. The update says treatment should be a team effort between patients and clinicians, be tailored to each person, and follow a planned, systematic process with regular…
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 paper is a clear review of how ketamine can lift severe depression quickly for some people and what we know about how it works in the brain. The authors say a single low-dose intravenous shot of ketamine can produce rapid and lasting antidepressant effects in people whose depression did…
This review explains how ketamine can lift depression symptoms much faster than standard antidepressants. Researchers describe the clinical results, how doctors usually give ketamine, and the brain changes it seems to cause. They also say that the treatment must be given carefully because small dose changes matter, the exact brain…
Researchers are studying whether brain scans taken before treatment can help pick the best treatment for people with major depression. They found that activity in one brain area (the fronto-insular cortex) at rest might tell who will do better with talk therapy versus medication, while high activity in another area…
This large review combined 441 randomized trials with 33,881 patients to measure how many people show a clear response to psychotherapy across eight mental disorders. Response was defined as at least a 50% reduction in symptoms from before to after treatment. Pooled response rates were modest (for example, about 42%…
