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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.

Mental Health Research Topics Ketamine Lack of energy or motivation

3 papers

Ketamine for Lack of energy or motivation

Based on 13 papers

Research shows that ketamine can lift depression symptoms much faster than usual antidepressants. Several randomized trials found benefits within hours to a day after treatment, especially for people whose depression did not get better with other medicines. A nasal form (esketamine) has also been approved for hard-to-treat depression in some cases. What is less certain is whether ketamine specifically fixes low energy or low motivation. Most studies measure overall depression scores, not single symptoms. Researchers also worry about short-term side effects and need more work on long-term safety, the best dosing plan, and whether combining ketamine with therapy or brain stimulation helps more or less.

Key findings

  • Many studies show ketamine can cut overall depression symptoms quickly, often within hours and with a peak around 24 hours after treatment. 15070 10152 10149 10146
  • A nasal form called esketamine was approved for treatment-resistant depression and has been shown in trials to reduce symptoms faster and more than a new antidepressant plus placebo spray. 15070 12156
  • Ketamine and esketamine can help some people whose depression did not improve after at least two antidepressant trials, but they do not work for everyone. 10153 10159 8950 10152
  • Common short-term side effects include brief dissociation (feeling disconnected), higher heart rate and blood pressure, headache, and dizziness. These effects usually go away within a few hours in studies. 10159 10153
  • The strength of evidence is mixed: several good randomized trials support quick, short-term benefit, but long-term effectiveness and the best maintenance plan are still unclear. 10152 12156 10159 10149 10153
  • Scientists do not fully agree how ketamine works. Leading ideas are that it blocks NMDA receptors and then raises AMPA activity and growth signals (like BDNF and mTOR) that help brain cells connect again. 10146 15070 10149
  • Most clinical studies measure overall depression scores, not single symptoms such as low energy or low motivation. That means we have limited direct evidence about how well ketamine improves energy or motivation alone. 10152 10159 10153 8950
  • Early research tests combining ketamine with other treatments (for example transcranial magnetic stimulation) or pairing drug sessions with psychotherapy. These ideas look promising but need more trials to prove they help. 10162 15065 15063 10159
  • Not all published results are reliable. At least one previously influential ketamine trial was retracted, which shows that the field still needs careful, high-quality studies. 10157

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

Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial

Colleen Loo, Nick Glozier, Dávid Barton, Bernhard T. Baune, Natalie Mills, Paul B. Fitzgerald, et al.
The British Journal of Psychiatry Summary & key facts 2023 60 citations

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…

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

RETRACTED ARTICLE: ArticleNoteRapid and sustained antidepressant effects of intravenous ketamine in treatment-resistant major depressive disorder and suicidal ideation: a randomized clinical trial

Ahmad Zolghadriha, Afagh Anjomshoaa, Mohammad Jamshidi, Farnaz Taherkhani
BMC Psychiatry Summary & key facts 2024 20 citations

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…

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