Psychiatry Research
January 1, 2025
David C J Chen-Li, Rodrigo B. Mansur, Joshua D. Di Vincenzo et al.
6 citations
In a real-world clinic setting, a single ketamine infusion significantly reduced suicidal ideation among 96 adults with treatment-resistant depression, as measured by the Columbia Suicide Severity Rating Scale. The reduction shifted the group average from active toward passive suicidal thoughts. A mediation analysis showed that ketamine's antisuicidal effects are partially independent of its antidepressant effects, suggesting a direct benefit on suicidality beyond mood improvement. The findings support ketamine's effectiveness for suicidal ideation outside controlled clinical trials.
JAMA Psychiatry
April 15, 2026
Diana Orsini, Sabrina Wong, Sara Di Luch et al.
4 citations
In randomized clinical trials of psychedelic drugs for psychiatric disorders, the drugs' strong subjective effects often reveal which treatment participants or raters think they received, a phenomenon called functional unblinding. A systematic review of 112 trials found that only 29.5% assessed whether blinding was maintained, yet 57.1% cited blinding as a limitation. Blinding failure exceeded 90% in psilocybin, LSD, and ayahuasca studies and 85% in MDMA trials with inert placebos. Ketamine trials rarely assessed blinding but fared better when midazolam was used as an active comparator. No control strategy consistently preserved ideal blinding, raising concerns about the validity of efficacy estimates.
Journal of Affective Disorders
December 15, 2024
Sabrina Wong, Gia Han Le, Rodrigo B. Mansur et al.
3 citations
A review of preclinical and clinical studies examined whether ketamine affects metabolic parameters, particularly glucose-insulin homeostasis, in people with major depressive disorder (MDD) and treatment-resistant depression (TRD). In experimental diabetic conditions, ketamine did not disrupt glucose-insulin homeostasis. In adults with MDD, ketamine was associated with GLUT3 transporter upregulation and altered metabolomic signatures. In adults with TRD, ketamine increased brain glucose uptake in the prefrontal cortex. The available evidence suggests ketamine does not adversely affect metabolic parameters, though few clinical studies have evaluated its effects on glucose-insulin homeostasis in MDD. Ketamine appears safe regarding metabolic disturbances commonly seen with other augmentation therapies.
The Journal of Clinical Psychiatry
July 7, 2025
Angela T H Kwan, Moiz Lakhani, Joshua D. Rosenblat et al.
2 citations
In a global pharmacovigilance analysis of adverse event reports from the World Health Organization's VigiBase database, esketamine was associated with higher reporting odds for suicidal ideation compared to lithium (5.13 times) and fluoxetine (3.34 times), while ketamine showed lower reporting odds for suicidal ideation, suicide attempt, and completed suicide relative to both reference drugs. Both drugs had lower reporting odds for suicide attempts and completed suicides. The authors caution that causality cannot be determined from these observational data.
Progress in Neuro-psychopharmacology and Biological Psychiatry
November 22, 2025
Shakila Meshkat, Noah Chisamore, Zoe Doyle et al.
A single dose of psilocybin was linked to small, temporary gains in processing speed and executive function in people with treatment-resistant depression. These cognitive improvements seemed unrelated to mood changes but did not consistently surpass the improvements expected from simply retaking the tests. The findings underscore the need for larger, controlled studies to determine whether psilocybin genuinely enhances cognition or if the observed changes stem from practice effects or mood shifts.
Neuroendocrinology
October 30, 2025
Sabrina Wong, Gia Han Le, Jens Uhlig et al.
Blocking NMDA receptors improves the function and survival of pancreatic alpha and beta cells, which may help explain why certain NMDA antagonists like ketamine, esketamine, and dextromethorphan have antidepressant effects and could also address metabolic problems often seen in depression. The findings suggest a shared mechanism linking mood regulation and pancreatic hormone control. More research is needed on how low doses of these drugs affect pancreatic function and delta cells.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
February 1, 2025
Danica E. Johnson, Nelson B Rodrigues, Sydney Weisz et al.
Depression with co-occurring posttraumatic stress disorder (PTSD) leads to more severe symptoms and poorer response to standard treatments. In a retrospective analysis of 134 patients with treatment-resistant depression, four ketamine infusions (0.5-0.75 mg/kg) reduced depressive symptoms equally in those with and without comorbid PTSD; no significant group-by-time interaction was found. PTSD symptoms also significantly improved across all symptom clusters, with moderate to large effect sizes. Ketamine shows promise as an effective intervention for this hard-to-treat population, though future randomized trials should explore factors driving improvement and long-term outcomes.
Journal of Affective Disorders
December 1, 2022
Anastasia Levinta, Shakila Meshkat, Roger S McIntyre et al.
Ketamine rapidly reduces depressive symptoms in people with treatment-resistant depression, but its effectiveness may diminish as the number of prior failed treatments increases. A systematic review of 18 randomized controlled trials found that ketamine and esketamine worked at both lower and higher stages of treatment resistance, yet effect sizes and duration of benefits were greater in studies involving patients with fewer prior antidepressant failures. Variability in how studies defined treatment resistance and measured outcomes prevented clear comparisons of efficacy across different resistance stages. The authors conclude that while ketamine remains broadly effective, more failed treatment trials may reduce its efficacy, and participant-level data are needed to clarify the relationship between resistance level and response.