Frontier mental health research: psychedelics & drug studies

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12 papers

Ketamine

Based on 42 papers

Researchers agree that ketamine can lift symptoms of major depression quickly for some people, often within hours to a day. Many trials show fast drops in suicidal thoughts and short-term mood improvement, but these effects usually fade over days to weeks unless treatment is repeated. Esketamine, a related nasal form, is approved for hard-to-treat depression and must be given in clinics with monitoring. Outside depression, scientists are testing ketamine for PTSD, anxiety, addiction, and other conditions. Early results are mixed or smaller for those problems. People still debate the best dose, how often to repeat treatments, how long benefits last, how much the drug experience or therapy around it matters, and what long-term risks (including possible misuse) might be.

Key findings

  • Ketamine can reduce depression symptoms very fast, sometimes within hours, and effects often peak around 24 hours after a single infusion. 10152 10149 15070
  • The antidepressant effect after one ketamine infusion usually lasts days to about two weeks, so many studies use repeated doses to keep benefits going. 12152 10149
  • Esketamine (a nasal spray) is approved for treatment-resistant depression and for depression with acute suicidal thoughts, and it must be given in a clinic with two-hour monitoring and blood-pressure checks. 10144 12156 15070
  • A common research method is an intravenous infusion of about 0.5 mg per kg over roughly 40 minutes; studies also test other routes like intranasal, subcutaneous, or intramuscular dosing. 10149 10159 12156 12152
  • Beyond depression, ketamine has shown early signs of helping with suicidal thoughts, PTSD, anxiety disorders, and some substance-use problems, but the evidence outside depression is smaller or less certain. 12152 9521 15068
  • Common short-term side effects include dissociation (a strange or detached feeling), sedation, higher blood pressure, dizziness, and brief psychosis-like sensations; these usually go away within a few hours. 12152 10159 10151 12156
  • Studies done under medical supervision report only a few clear cases of tolerance or dependence, so the addiction risk in clinical use seems low, but researchers say long-term risk is still uncertain. 8828 12152 12365
  • Scientists have evidence about how ketamine works, such as blocking NMDA receptors and boosting AMPA signaling, BDNF, and mTOR pathways that support brain plasticity, but the exact chain of events is still being worked out. 10147 10146 10148 9521 15070
  • Many published ketamine studies are small or have risks of bias, so experts call for larger, longer trials to answer questions about long-term safety, optimal dosing plans, and which patients will benefit most. 12152 10153 15129

Antidepressant effects of ketamine in depressed patients

Robert Berman, Angela Cappiello, Amit Anand, Dan A. Oren, George R. Heninger, Dennis S. Charney, et al.
Biological Psychiatry Summary & key facts 2000 3,784 citations

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…

Functional Brain Connectivity Studies Treatment of Major Depression Tryptophan and brain disorders Ketamine

Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial

James W. Murrough, Dan V. Iosifescu, Lee C. Chang, Rayan K. Al Jurdi, Charles E. Green, Andrew M. Perez, et al.
American Journal of Psychiatry Summary & key facts 2013 1,186 citations

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…

Neuroscience and Neuropharmacology Research Treatment of Major Depression Tryptophan and brain disorders Ketamine

Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study

Vanina Popova, Ella Daly, Madhukar H. Trivedi, Kimberly Cooper, Rosanne Lane, Pilar Lim, et al.
American Journal of Psychiatry Summary & key facts 2019 839 citations

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…

Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes Treatment of Major Depression Tryptophan and brain disorders Ketamine

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

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

Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression

Amit Anand, Sanjay J. Mathew, Gerard Sanacora, James W. Murrough, Fernando S. Goes, Murat Altinay, et al.
New England Journal of Medicine Summary & key facts 2023 233 citations

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…

Electroconvulsive Therapy Studies 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.

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

Is there a risk of addiction to ketamine during the treatment of depression? A systematic review of available literature

Gianmarco Ingrosso, Anthony J. Cleare, Mário F. Juruena
PubMed Summary & key facts 2025 13 citations

This systematic review looked at 16 studies of ketamine used to treat adults with depression, covering 2,174 patients. The authors found few clear cases of tolerance or dependence (four patients) and conclude that, overall, ketamine appears relatively safe for depression when given under medical supervision, with careful monitoring and dosing.…

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

The Role of Ketamine in Treatment-resistant Depression: A Narrative Review

Ashwini Reddy, Swati Patel, Amiya Kumar Barik, Priya Thappa, Kiran Jangra, Kirandeep Kaur, et al.

SPRAVATO (esketamine) is a prescription nasal spray for adults with treatment‑resistant depression to be used together with an oral antidepressant. It must be given and watched by a healthcare provider because it can cause sedation, dissociation, and increases in blood pressure. Patients are observed for at least two hours after…

Stress Responses and Cortisol Treatment of Major Depression Tryptophan and brain disorders Ketamine

Comparing the Cognitive Effects of Repeated Intravenous Ketamine and Electroconvulsive Therapy in Patients With Treatment-Resistant Depression

Kristina T. Kumpf, Samuel T. Wilkinson, Bo Hu, Ruoying Chen, Kamini Krishnan, Shinjon Chakrabarti, et al.

This secondary analysis of a multisite randomized trial compared cognitive effects of repeated IV ketamine (six treatments) and electroconvulsive therapy (nine sessions) in 365 people with treatment-resistant depression. After the 3-week treatment course, the ECT group did worse than the ketamine group on four objective cognitive tests (P < .001).…

Electroconvulsive Therapy Studies Perfectionism, Procrastination, Anxiety Studies Treatment of Major Depression Ketamine
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