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27 papers
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…
Compass Pathways reported early results from its first Phase 3 trial of synthetic psilocybin (COMP360) for treatment‑resistant depression. In 258 patients, the 25 mg dose showed a statistically significant improvement versus placebo on the MADRS depression scale at week 6 (a 3.6‑point difference, p < 0.001). The Data and Safety…
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…
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…
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 tested deep brain stimulation (DBS) in a small group of people whose depression did not get better with usual treatments. They used an implanted device that both delivered stimulation to the subcallosal cingulate (a brain area linked to mood) and recorded brain electrical signals. Around 9 out of 10…
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 pooled results from 205 intravenous ketamine infusions (0.5 mg/kg given over 40 minutes) in 97 people with treatment-resistant major depression. About two thirds (67%, 65 of 97) showed a strong antidepressant response (≥50% improvement). Most side effects happened in the first 4 hours and were short-lived. Few infusions were…
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…
