Frontiers in Psychiatry
February 10, 2023
Muhammad Ishrat Husain, Nicole Ledwos, Elise Fellows et al.
47 citations
A narrative review examined the neurobiological mechanisms that may explain the rapid antidepressant effects of serotonergic psychedelics such as psilocybin, LSD, and ayahuasca. The drugs act as agonists or partial agonists at serotonin 5HT2A receptors, and their rapid effects may involve downregulation of these receptors. They also influence brain-derived neurotrophic factor and immune responses. Neuroimaging studies suggest that psychedelics may disrupt the default mode network, a brain system involved in self-referential thinking that is overactive in major depressive disorder. The review concludes that multiple competing theories are being investigated and more research is needed to identify the most robust evidence.
Journal of clinical psychopharmacology
Nicole Ledwos, Joshua D Rosenblat, Daniel M Blumberger et al.
16 citations
A critical appraisal of clinical trials on serotonergic psychedelics for major depressive disorder and end-of-life distress finds that current evidence is low-level due to methodological limitations. Small randomized trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy to an active comparator, with similar preliminary positive effects for single-dose ayahuasca in treatment-resistant depression and lysergic acid diethylamide for end-of-life distress. Adverse events were mild and transient. However, small homogenous samples, expectancy bias, functional unblinding, and lack of standardized psychotherapy limit all studies. Psychedelics should remain experimental interventions used within clinical trials.
EClinicalMedicine
December 1, 2025
Tyler S Kaster, Yi Dai, Fidel Vila-Rodriguez et al.
5 citations
Both repetitive transcranial magnetic stimulation (rTMS) and intranasal esketamine are more effective than starting a new antidepressant medication for treatment-resistant depression. In a secondary analysis of individual patient data from two clinical trials involving 282 matched participants, rTMS reduced depression severity scores by 5.35 points and esketamine by 2.89 points more than medication alone. The difference between rTMS and esketamine was not statistically significant, but the results suggest rTMS may be at least as effective as esketamine. The analysis highlights the need for direct head-to-head trials comparing these two interventions.
The Journal of clinical psychiatry
January 8, 2025
Ali Abdolizadeh, Brett D M Jones, Maryam Hosseini Kupaei et al.
2 citations
A systematic review of treatments for suicidality among psychiatric inpatients aged 18–65 found that intravenous ketamine produced the most consistent rapid reduction in suicidality among 14 pharmacologic trials. Among 35 nonpharmacologic trials—including chronotherapy, neurostimulation, and psychotherapies—results were mixed, with some interventions showing potential benefit, especially for mood, personality, and trauma-related disorders. Many studies had methodological limitations such as nonrandomized designs and lack of control groups. The review calls for larger, well-designed trials to confirm effectiveness.
PloS one
January 1, 2025
Johny Bozdarov, Brett D M Jones, Madeha Umer et al.
2 citations
A 10-week trial of Mindfulness-Based Boxing Therapy (MBBT) for adults with major depressive disorder or generalized anxiety disorder showed high retention (89%), attendance (84%), and satisfaction (98%). Among eight outpatients in Toronto, depression scores dropped 54%, anxiety 51%, and distress 36%, while mindfulness increased 79%. Participants reported benefits including cathartic release, improved self-esteem, and a sense of community. The authors conclude that MBBT is feasible and acceptable as an exercise-based intervention, but caution that larger randomized trials are needed to confirm clinical benefits.
Journal of affective disorders
January 23, 2026
Reinhard Janssen-Aguilar, Jithin Joseph, Huda Al-Shamali et al.
In a retrospective chart review of 209 adults with treatment-resistant depression treated with intravenous ketamine, depressive and anxiety symptoms improved significantly over four or six infusions, but the improvements were modest and highly variable across individuals. Anxiety symptoms improved more slowly and less robustly than depressive symptoms. End-of-treatment response and remission rates were numerically higher after six infusions than after four, but the difference was not statistically significant. Four distinct patterns of symptom change emerged for both depression and anxiety, highlighting the heterogeneity of treatment response. Durability after six infusions could not be assessed because follow-up data were available only for the four-infusion group.