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24 papers
Researchers are testing many ways to help people who feel low energy or low motivation, often as part of treating depression. The clearest, strongest evidence right now is for ketamine and its close relative esketamine. These drugs can reduce depressive symptoms quickly for some people who did not get better with usual medicines. Regular physical activity, especially walking, also has good evidence for reducing depressive symptoms and may help energy over time. Other approaches look promising but are still early-stage. Psychedelic-assisted psychotherapy (drugs like psilocybin or MDMA given together with careful therapy) shows encouraging results in trials but needs more research and detailed therapy support. Brain-based treatments such as deep brain stimulation (DBS) or combining brain stimulation with ketamine are experimental but may help some people who have not responded to many other treatments. Whole-body hyperthermia (controlled heating) is very preliminary and needs careful testing and safety checks. Across all options, safety, careful preparation, and close follow-up are important because effects and risks vary between people.
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 umbrella review pooled evidence from 97 systematic reviews (1,039 randomized trials, 128,119 participants) to examine whether physical activity affects symptoms of depression, anxiety and psychological distress in adults. Overall, physical activity produced medium-sized reductions in symptoms (median effect size for depression = -0.43, for anxiety = -0.42; distress effect…
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 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…
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 2017 clinical review explains how bipolar I and II disorders are diagnosed and treated. It says bipolar illness involves swings between manic (or hypomanic) and depressive episodes. Treatment usually needs both medicines and psychosocial therapy, and care must be adjusted over time because relapses and incomplete responses — especially…
This paper reviews clinical and lab studies about psychedelic therapy, which means using a psychedelic drug together with psychological support. The authors say this approach looks promising for several different mental health problems that share rigid or harmful patterns of feeling, thinking, or acting — especially major depression, depression that…
