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…

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l’humeur et de l’anxiété (CANMAT) 2023 : Mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes

Raymond W. Lam, Sidney H. Kennedy, G. Camelia Adams, Anees Bahji, Serge Beaulieu, Venkat Bhat, et al.

The Canadian Journal of Psychiatry • Summary & key facts • 2024 • 240 citations

The CANMAT 2023 update gives doctors clear, up-to-date advice for treating adults with major depressive disorder. It puts evidence into a practical, clinician-friendly format. The update says treatment should be a team effort between patients and clinicians, be tailored to each person, and follow a planned, systematic process with regular…

Ketamine Safety and Tolerability in Clinical Trials for Treatment-Resistant Depression

Le-Ben Wan, Cara F. Levitch, Andrew M. Perez, Jess W. Brallier, Dan V. Iosifescu, Lee C. Chang, et al.

The Journal of Clinical Psychiatry • Summary & key facts • 2014 • 230 citations

Researchers pooled results from 205 intravenous ketamine infusions (0.5 mg/kg given over 40 minutes) in 97 people with treatment-resistant major depression. About two thirds (67%, 65 of 97) showed a strong antidepressant response (≥50% improvement). Most side effects happened in the first 4 hours and were short-lived. Few infusions were…

Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review

Zach Walsh, Özden Merve Mollaahmetoğlu, Joseph M. Rootman, Shannon Golsof, Johanna Louise Keeler, Beth Marsh, et al.

BJPsych Open • Summary & key facts • 2021 • 168 citations

This systematic review looked at 83 published reports on ketamine for mental health and substance use disorders. It found strong evidence that ketamine can produce rapid antidepressant and anti‑suicidal effects, but these benefits tend to be short‑lived. Evidence for other conditions was weaker but often showed similar short-term effects. Many…

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…

Ketamine Assisted Psychotherapy: A Systematic Narrative Review of the Literature

Sandra J Drozdz, Akash Goel, Matthew W McGarr, Joel Katz, Paul Ritvo, Gabriella Mattina, et al.

PubMed • Summary & key facts • 2022 • 92 citations

This systematic review looked at 17 studies with a total of 603 participants on ketamine-assisted psychotherapy (KAP). The reviewed reports say KAP can, in some cases, start and lengthen meaningful reductions in pain, anxiety, and depression, and help with rapport, treatment engagement, and abstinence for people with substance problems. However,…

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