Frontier mental health research: psychedelics & drug studies

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…

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…

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…

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…

Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials

Joanna Kryst, Paweł Kawalec, Alicja Mikrut Mitoraj, Andrzej Pilc, Władysław Lasoń, Tomasz Brzostek

PubMed • Summary & key facts • 2020 • 145 citations

This meta-analysis combined 20 randomized clinical trials up to February 22, 2019, and found that a single dose of ketamine produced rapid antidepressant effects that were strongest at 24 hours and that these effects were still detectable up to 7 days. The analysis also found that repeated ketamine doses helped…

Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression

Samuel T. Wilkinson, DaShaun Wright, Madonna Fasula, Lisa R. Fenton, Matthew Griepp, Robert Ostroff, et al.

Psychotherapy and Psychosomatics • Summary & key facts • 2017 • 115 citations

This small open-label study tested whether a 12-session course of cognitive behavioral therapy (CBT) given alongside four intravenous ketamine infusions could help maintain ketamine's antidepressant effects in people with treatment-resistant depression. Sixteen patients started the study; 8 (50%) responded to ketamine and 7 (43.8%) reached remission in the first two…

A randomized, double-blind, active placebo-controlled study of efficacy, safety, and durability of repeated vs single subanesthetic ketamine for treatment-resistant depression

Paulo Shiroma, Paul Thuras, Joseph Wels, C. Sophia Albott, Christopher R. Erbes, Susannah J. Tye, et al.

Translational Psychiatry • Summary & key facts • 2020 • 104 citations

This randomized, double-blind trial tested whether six low-dose ketamine infusions over 12 days worked better than a single ketamine infusion for people with treatment-resistant depression. At 24 hours after the last infusion, there was no significant difference in clinician-rated depression scores between the group that received six ketamine infusions and…

Efficacy of ketamine therapy in the treatment of depression

Suprio Mandal, Vinod Kumar Sinha, Nishant Goyal

PubMed Central (PMC) • Summary & key facts • 2019 • 90 citations

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…

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…

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.…

Long-term outcomes of repeated ketamine infusions in patients with unipolar and bipolar depression: A naturalistic follow-up study

Weicheng Li, Yanling Zhou, Weijian Liu, Chengyu Wang, Xiaofeng Lan, Zhipei Zhang, et al.

Journal of Affective Disorders • Summary & key facts • 2021 • 13 citations

Researchers followed 108 people with unipolar or bipolar depression who had repeated ketamine infusions (three times weekly over 12 days) and then were observed for 9 months. Depression symptoms and overall function were measured with the PHQ‑9 and the GAF. Seventy‑one people (65.7%) completed the full 9‑month follow‑up. At month…