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.
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.