Frontier mental health research: psychedelics & drug studies

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4 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

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

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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