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Frontier mental health research: psychedelics & drug studies

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.

Ketamine Sadness or low mood Intensive care medicine

3 papers

Ketamine for Sadness or low mood

Based on 33 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.

Key findings

  • Ketamine can reduce depressive symptoms quickly, sometimes within hours and with clear improvement by about 24 hours. 15070 10149 10152
  • The benefit after a single ketamine infusion often peaks around 24 hours and commonly fades over about one to two weeks unless repeated doses are given. 15070 10149
  • A nasal form of ketamine called esketamine has been approved for treatment-resistant depression and has shown faster and larger symptom drops when combined with an oral antidepressant in trials. 15070 12156
  • Ketamine can help some people labeled 'treatment-resistant' who did not get better with at least two standard antidepressant trials. 10153 8950 10152
  • Repeated or flexible dosing schedules can increase the number of people who reach remission, but research shows results vary and practices differ between clinics. 10159 10149
  • Short-term side effects often include dissociation (strange or dreamlike feelings), brief increases in blood pressure, faster heart rate, headache, and dizziness. These usually pass within hours in clinical studies. 10159 12156 10153
  • Researchers agree the evidence is strongest for short-term benefits, but many trials are small or short, so long-term safety and how long benefit lasts are still uncertain. 10153 10151 15064
  • At the brain level, ketamine mainly affects the glutamate system (blocking NMDA receptors and increasing AMPA activity), which may boost connections between neurons and activate growth-related signals; however, some blood markers (like BDNF) do not consistently change in human studies. 10146 10147 10148 15129
  • Non-drug factors matter. A person’s mindset, the treatment setting, preparation, and what they were exposed to beforehand can shape the ketamine experience and possibly the outcome. 15065 15075 15096
  • Experts and patients raise concerns about long-term risks, possible misuse, how to monitor treatment, and the need for clearer public information and more research before wider rollout. 10153 12365 15087 15085

Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation

Roger S. McIntyre, Joshua D. Rosenblat, Charles B. Nemeroff, Gerard Sanacora, James W. Murrough, Michael Berk, et al.
American Journal of Psychiatry Summary & key facts 2021 646 citations

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…

Mental Health Research Topics Treatment of Major Depression Tryptophan and brain disorders Ketamine

Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions

Roger S. McIntyre, Mohammad Alsuwaidan, Bernhard T. Baune, Michael Berk, Koen Demyttenaere, Joseph F. Goldberg, et al.
World Psychiatry Summary & key facts 2023 586 citations

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…

Electroconvulsive Therapy Studies Transcranial Magnetic Stimulation Studies Treatment of Major Depression Ketamine

Management of Treatment-Resistant Depression: Challenges and Strategies

Daphne Voineskos, Zafiris J. Daskalakis, Daniel M. Blumberger
Neuropsychiatric Disease and Treatment Summary & key facts 2020 411 citations

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…

Electroconvulsive Therapy Studies Treatment of Major Depression Tryptophan and brain disorders Ketamine Psilocybin
Summaries and links are for general information and education only. They are not a substitute for reading the original publication or for professional medical, legal, or other advice. Always refer to the linked source for the full study.