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.
Lancet (London, England)
July 22, 2025
Balwinder Singh, Holly A Swartz, Alfredo B Cuellar-Barboza et al.
66 citations
Bipolar disorder, marked by hypomania or mania and predominantly depression, affects about 40 million people worldwide and carries substantial psychosocial, medical, and financial burdens, along with increased suicide risk. Diagnosis is often delayed due to symptom overlap with ADHD, major depression, psychotic disorders, and personality disorders. Recent research points to multigene risk and possible infectious and mitochondrial causes. Treatment combines pharmacotherapy, psychotherapy, and lifestyle changes, tailored to individual goals. Future priorities include expanding self-management psychosocial interventions, addressing treatment-resistant depression, deepening understanding of pathophysiology, and exploring novel options like ketamine, esketamine, and neuromodulation.
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).
Trials
July 3, 2024
Joshua M Poulin, Gregory E Bigford, Krista L Lanctôt et al.
3 citations
A proposed randomized controlled trial will test whether a single 25 mg dose of psilocybin, compared to a placebo, acutely alters cerebral blood flow and functional brain activity in mood-regulating networks in people with major depressive disorder or persistent depressive disorder. Fifty participants from a mood disorders clinic will be randomly assigned to receive either psilocybin or a placebo, with the placebo group later crossing over to receive psilocybin. The study will use arterial spin labelling and blood oxygenation level-dependent functional MRI to measure brain changes intraday and at three weeks. Clinical outcomes will be tracked with the Montgomery-Åsberg Depression Rating Scale and other scales. The work aims to clarify psilocybin's neuroplastic mechanisms and identify early brain-based predictors of treatment response.
Research Square
December 28, 2023
Joshua M. Poulin, Gregory E. Bigford, Krista L. Lanctôt et al.
1 citation
About one third of people with depression do not fully respond to standard treatments, and psilocybin may offer a rapid-acting alternative. This registered trial will randomize 36 adults with major depressive or persistent depressive disorder to receive either 25 mg psilocybin or an active placebo (100 mg niacin), then cross over three weeks later so that all participants receive psilocybin. Using serial neuroimaging, the study will test whether psilocybin acutely alters cerebral blood flow and functional brain activity in mood-related networks compared to placebo, and whether those changes persist subacutely. Clinical scales and serum biomarkers will also be collected to explore relationships with treatment response.
Bipolar disorders
May 1, 2023
William S H Kim, Mikaela K Dimick, Danielle Omrin et al.
In a double-blind randomized controlled trial, 25 adults with bipolar I or II disorder and treatment-resistant depression received either nitrous oxide (25% concentration for 20 minutes) plus intravenous saline or medical air plus intravenous midazolam (2 mg total). No significant between-group differences emerged in depression severity change or treatment response 24 hours after treatment. However, the nitrous oxide group showed significantly greater same-day reductions in depression severity. Lower baseline regional cerebral blood flow predicted greater 24-hour improvement with nitrous oxide but not midazolam. Midazolam was associated with regional cerebral blood flow reductions compared to nitrous oxide. These secondary findings suggest differential associations of the two agents with depression severity and brain hemodynamics, warranting larger studies.
Contemporary clinical trials communications
September 1, 2020
Mikaela K Dimick, Danielle Omrin, Bradley J MacIntosh et al.
A randomized, double-blind trial will test whether a single administration of nitrous oxide (N2O) improves mood and increases frontal cerebral blood flow in adults with treatment-resistant bipolar depression. Participants with bipolar I or II disorder currently in a major depressive episode will be assigned to either inhaled N2O plus intravenous saline or inhaled room air plus intravenous midazolam. Mood will be assessed with the Montgomery-Asberg Depression Rating Scale, and cerebral blood flow measured by arterial spin labelling MRI. The authors suggest N2O may act as a cerebral vasodilator to counteract hypoperfusion in depression, and if effective, could become a low-cost, safe, and accessible acute treatment.