The Canadian Journal of Psychiatry
November 11, 2020
Jennifer Swainson, Alexander McGirr, Pierre Blier et al.
109 citations
A systematic review by the Canadian Network for Mood and Anxiety Treatments evaluated evidence for racemic ketamine in treatment-resistant depression. Single intravenous infusions have Level 1 evidence for efficacy in adults, while multiple or maintenance infusions have only Level 3 evidence. Adverse events include dissociative symptoms and hypertension. Non-IV formulations have Level 3 or 4 evidence. Single-dose IV racemic ketamine is a third-line recommendation; repeated use requires careful case-by-case risk-benefit assessment. Oral and other formulations should be limited to specialists with ketamine expertise at tertiary centers due to limited evidence and risk of misuse.
The Canadian Journal of Psychiatry
August 17, 2022
Joshua D. Rosenblat, Muhammad Ishrat Husain, Yena Lee et al.
58 citations
Serotonergic psychedelics are being reconsidered as potential treatments for major depressive disorder. A Canadian task force systematically reviewed clinical trials from 1990 to 2021 and found that only psilocybin and ayahuasca have been tested in contemporary studies. Two pilot studies of single-dose ayahuasca for treatment-resistant depression showed preliminary positive effects (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy for major depressive disorder showed superiority to waitlist controls and comparable efficacy and safety to escitalopram with supportive psychotherapy, with additional trials showing efficacy in cancer-related depression (Level 3 evidence).
Brain and Behavior
November 25, 2021
Elise M Hawkins, William Coryell, Stephen Leung et al.
25 citations
Lithium and clozapine are the only two somatic treatments with high-quality evidence of reducing suicide risk, in mood disorders and schizophrenia respectively; stopping lithium increases that risk. Ketamine and esketamine may offer a small, immediate antisuicide effect, though a disproportionate number of suicides occurred in esketamine-treated subjects versus placebo (3 vs. 0 among over 3500 subjects), requiring ongoing evaluation. The evidence for electroconvulsive therapy's antisuicide effect is low-quality. Antidepressants' effect is unclear: direct evidence shows they may increase suicidal ideation and risk in young people over the short term, while indirect evidence suggests they reduce risk over the long term. Clinicians have an expanding pharmacopeia, but some agents may also increase suicidality under specific circumstances.
Psychiatry Research
May 1, 2024
Balwinder Singh, Sagar V Parikh, Jennifer L. Vande Voort et al.
18 citations
In a nonrandomized, open-label clinical trial, 74 adults with treatment-resistant depression received three intravenous ketamine infusions, with an additional four infusions for those who remitted. After the acute phase, 53% (39/74) experienced remission of depression symptoms. Higher baseline language domain scores on the RBANS cognitive assessment were associated with greater odds of remission. No significant association was found between remission and baseline immediate or delayed memory, visuospatial, or attention scores. During the continuation phase, improvements in immediate and delayed memory and attention persisted, with additional gains in visuospatial and language domains. The findings suggest cognitive improvement, not deterioration, with serial ketamine administration.
The Journal of Clinical Psychiatry
August 26, 2024
Rachel M Pacilio, Juan F Lopez, Sagar V Parikh et al.
7 citations
Many women who could become pregnant receive ketamine for psychiatric conditions, but risks to a developing fetus are frequently overlooked. A survey of U.S. outpatient ketamine clinics found that fewer than half discuss pregnancy-related risks during informed consent, only 20% require pregnancy tests before treatment, and just 13.7% recommend or require contraception. A record review at one academic medical center showed all patients were tested weekly for pregnancy, but only half used contraception. The findings indicate a need for greater attention to reproductive health in ketamine treatment protocols.
Journal of Affective Disorders
September 15, 2025
Brandan K Penaluna, Jennifer L. Vande Voort, William V Bobo et al.
4 citations
In people with treatment-resistant depression, intravenous ketamine improved symptoms across four depression subtypes: Sadness, Negative Thoughts, detachment/Interest and Activity, and Neurovegetative. After three infusions over 11 days, 53% of the 75 participants achieved remission. The Negative Thoughts subtype showed the least improvement, and the Neurovegetative subtype was the least responsive overall. Higher baseline Sadness scores were linked to lower remission rates, and a positive Sadness phenotype reduced the odds of remission (odds ratio 0.32). No meaningful sex differences in response were found by the end of treatment.
The Journal of Clinical Psychiatry
May 26, 2025
Rachel M Pacilio, Sagar V Parikh, Jamarie Geller
4 citations
Ketamine is increasingly used for psychiatric disorders outside academic settings, but little is known about real-world practices. A survey of U.S. community-based ketamine clinics and a review of their websites found that all clinics use ketamine for treatment-resistant depression, and many also prescribe it for treatment-naive depression (72.3%), bipolar depression (78.9%), and subclinical depression (59.7%). Over 80% of clinics offer maintenance treatment, often for prolonged periods, and over 40% provide ketamine for at-home use. Fewer than 30% of clinics are run by psychiatric physicians, and over 25% by nonphysician providers. The findings indicate significant variability in indications, duration, formulations, and settings, highlighting a need for increased oversight and specific practice guidelines.
Contemp Clin Trials
March 2, 2026
Samuel T. Wilkinson, Sandhya Prashad, Rachel Dalthorp et al.
1 citation
The EQUIVALENCE trial protocol describes a non-inferiority, comparative effectiveness study designed to test whether intranasal esketamine is no less effective than intravenous ketamine for treating treatment-resistant depression. The study will compare the two treatments head-to-head in patients who have not responded to prior antidepressant therapies. The protocol outlines the trial's design, including randomization, dosing regimens, outcome measures, and statistical analysis plan. By directly comparing these two forms of ketamine, the trial aims to provide evidence on whether the more convenient intranasal route can match the efficacy of the intravenous formulation, potentially offering a more accessible treatment option.
Biological Psychiatry Global Open Science
July 1, 2025
Stephen A Murata, Zachary B Madaj, Colt D Capan et al.
1 citation
Higher baseline levels of anthranilic acid (AA), a metabolite in the kynurenine pathway, predicted remission in patients with treatment-resistant depression receiving intravenous ketamine. In an open-label trial of 74 patients, 52% achieved remission after three infusions. Composite ratios of AA to intercellular adhesion molecule-1 and AA to tryptophan improved predictive accuracy over AA alone. The findings suggest that immunometabolic biomarkers could guide personalized ketamine treatment.