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.

37 papers

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

A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression

Carlos A. Zarate, Jaskaran Singh, Paul J. Carlson, Nancy E. Brutsché, Rezvan Ameli, David A. Luckenbaugh, et al.
Archives of General Psychiatry Summary & key facts 2006 3,698 citations

In a small, controlled study of 18 people with treatment-resistant major depression, a single intravenous dose of the NMDA receptor antagonist ketamine (0.5 mg/kg) produced rapid drops in depression scores. Improvement began within about 2 hours and remained statistically significant compared with placebo for up to 1 week. The study…

Neurotransmitter Receptor Influence on Behavior Treatment of Major Depression Tryptophan and brain disorders

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

Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression

Ella Daly, Madhukar H. Trivedi, Adam Janik, Honglan Li, Yun Zhang, Xiang Li, et al.
JAMA Psychiatry Summary & key facts 2019 726 citations

This phase 3, double-blind trial tested whether continuing esketamine nasal spray plus an oral antidepressant could delay relapse in adults with treatment-resistant depression who had already improved after an initial esketamine course. Of 297 patients who entered the randomized phase, continuing esketamine reduced relapse compared with switching to placebo nasal…

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

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

Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial

Michael F. Grunebaum, Hanga Galfalvy, Tse‐Hwei Choo, John G. Keilp, Vivek K. Moitra, Michelle S. Parris, et al.
American Journal of Psychiatry Summary & key facts 2017 412 citations

Adjunctive ketamine demonstrated a greater reduction in clinically significant suicidal ideation in depressed patients within 24 hours compared with midazolam, partially independently of antidepressant effect.

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

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

Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial

Jennifer L. Phillips, Sandhaya Norris, Jeanne Talbot, Meagan Birmingham, Taylor Hatchard, Abigail Ortiz, et al.
American Journal of Psychiatry Summary & key facts 2019 396 citations

Repeated ketamine infusions have cumulative and sustained antidepressant effects. Reductions in depressive symptoms were maintained among responders through once-weekly infusions. These findings provide novel data on efficacious administration strategies for ketamine in patients with treatment-resistant depression. Future studies should further expand on optimizing administration to better translate the use of…

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

Core symptoms of major depressive disorder: relevance to diagnosis and treatment

Sidney H Kennedy
PubMed Central (PMC) Summary & key facts 2008 370 citations

Major depressive disorder (MDD) is defined without assuming a single cause and has two main symptoms: depressed mood and loss of interest or pleasure. The paper says we should also pay more attention to fatigue, sleep problems, anxiety, thinking (cognitive) problems, and sexual problems when diagnosing and judging treatment. Some…

Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes Mental Health Research Topics Treatment of Major Depression

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
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