Frontier mental health research: psychedelics & drug studies

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…

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…

Ketamine for chronic pain: risks and benefits

Marieke Niesters, Christian Martini, Albert Dahan

British Journal of Clinical Pharmacology • Summary & key facts • 2013 • 485 citations

Ketamine, an anaesthetic, can reduce chronic pain, especially pain with nerve damage. Low doses give strong pain relief, probably by blocking NMDA receptors. Short infusions tend to help only while the drug is given, but three studies found that longer infusions (4–14 days) produced pain relief lasting up to 3…

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…

Adjunctive Ketamine With Relapse Prevention–Based Psychological Therapy in the Treatment of Alcohol Use Disorder

Meryem Grabski, Amy McAndrew, Will Lawn, Beth Marsh, Laura Raymen, Tobias Stevens, et al.

American Journal of Psychiatry • Summary & key facts • 2022 • 152 citations

This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.

Neurocognitive effects of ketamine in treatment-resistant major depression: association with antidepressant response

James W. Murrough, Le-Ben Wan, Brian M. Iacoviello, Katherine A. Collins, Carly Solon, Benjamin S. Glicksberg, et al.

Psychopharmacology • Summary & key facts • 2013 • 107 citations

This small open-label study tested 25 people with treatment-resistant major depression who each received one intravenous ketamine infusion (0.5 mg/kg over 40 minutes). The researchers found that people who showed an antidepressant response at 24 hours had worse thinking skills before treatment, especially slower processing speed. Ketamine caused short-term problems…

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

Esketamine for treatment‑resistant depression: A review of clinical evidence (Review)

Octavian Vasiliu

Experimental and Therapeutic Medicine • Summary & key facts • 2023 • 69 citations

This review looked at 14 clinical papers about esketamine for adults whose depression did not get better after usual treatment. It found that most studies support using esketamine as an add-on to standard antidepressants for treatment‑resistant depression, but the evidence about long‑term benefit and safety is limited. Some trials did…

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…

A case series of group-based ketamine-assisted psychotherapy for patients in residential treatment for eating disorders with comorbid depression and anxiety disorders

Reid Robison, Adèle Lafrance, Madeline Brendle, Michelle Smith, Claire E. Moore, Sachin Ahuja, et al.

Journal of Eating Disorders • Summary & key facts • 2022 • 31 citations

This small case series tested group-based ketamine-assisted psychotherapy (G-KAP) with five women in a residential eating-disorder program. Participants got weekly intramuscular ketamine in a group for 4 weeks. Four of five showed clinically meaningful drops in depression scores after the final session, and two of five showed clinically meaningful drops…

Ketamine for treatment-resistant obsessive-compulsive disorder: Double-blind active-controlled crossover study

Ben Beaglehole, Paul Glue, Shona Neehoff, Shabah M. Shadli, Neil McNaughton, Bridget Kimber, et al.

Journal of Psychopharmacology • Summary & key facts • 2024 • 8 citations

We provide further preliminary evidence for the efficacy and tolerability of IM ketamine in an outpatient cohort of OCD. Additional work is required to establish the optimal dosing regimen and longer-term role of ketamine for OCD. These findings are encouraging given the well-known limitations that exist for treatments in this…

Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm

Henry A. MacConnel, Mitch Earleywine, Steven Radowitz

Journal of Psychopharmacology • Summary & key facts • 2024 • 5 citations

This retrospective study looked at 117 outpatients with high PTSD Checklist (PCL-5) scores who received at least six intravenous ketamine sessions given in a supportive, “psychedelic” style (preparation, intention-setting, eye shades, evocative music, and integration). Average PCL-5 scores fell from 52.54 (SD = 12.01) to 28.78 (SD = 16.61), a…