Psychiatry research
March 1, 2025
Juliana Lima Constantino, Martijn Godschalk, Jens H van Dalfsen et al.
14 citations
About half of people with treatment-resistant depression do not respond to (es)ketamine, despite its known efficacy. This systematic review of 44 studies examined whether demographic or clinical traits predict who will respond or remit after (es)ketamine treatment. Overall, most demographic and clinical variables showed no consistent predictive value. Preliminary evidence linked better response to anhedonia, sleep disturbances, childhood physical abuse, obesity, openness, better episodic memory and visual learning, poorer neurocognitive performance, slower processing speed, and lower attention, while melancholic depression, benzodiazepine use, and metabolic syndrome were linked to worse response. These associations need replication, but suggest (es)ketamine may benefit patients with characteristics often considered hard to treat.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2025
Juliana Lima Constantino, Jens H van Dalfsen, Sara Massetti et al.
6 citations
A systematic review of nine studies found that psilocybin consistently decreases interleukin-6, C-reactive protein, and eosinophils, and increases cortisol, prolactin, oxytocin, thyroid-stimulating hormone, adrenocorticotropic hormone, brain-derived neurotrophic factor, and free fatty acids in healthy participants. These biomarker changes align with preclinical evidence and suggest psilocybin may have beneficial effects on biological processes involved in major depressive disorder. However, results are preliminary due to the small number of studies and exclusive use of healthy volunteers. Further research with clinical populations, larger samples, and longer follow-up is needed before drawing firm conclusions.
Journal of affective disorders
September 15, 2026
Rutger Boesjes, Claudia Oosterveld, Jeanine Kamphuis et al.
1 citation
Ketamine and its enantiomers show rapid antidepressant effects for major depressive disorder and bipolar disorder, but responses vary widely. This systematic review of 26 studies (1694 participants) found that ketamine treatment is linked to improved subjective sleep quality. Preliminary evidence suggests that baseline sleep disturbances and early sleep improvements may predict antidepressant response. Some studies also indicate beneficial effects on objective sleep and circadian rhythmicity, but this finding is tentative due to few published articles. The authors call for more research on objective circadian measures and potential synergy with chronotherapies.
Psychiatry research
March 1, 2026
Gijsbrecht H J Roelandt, Jurriaan F M Strous, Radboud M Marijnissen et al.
1 citation
A single open-label dose of 75 mg intranasal racemic ketamine was tested in 12 acutely suicidal patients in an emergency setting, regardless of underlying diagnosis. The treatment was generally feasible, well-tolerated, and safe. Scores for suicidal ideation and depression showed a downward trend one day after treatment, but this effect declined by day seven. One patient developed ketamine misuse several weeks after participation. No definitive conclusions about efficacy could be drawn from this pilot study.
International journal of methods in psychiatric research
December 1, 2025
Jurriaan F M Strous, Gijs H J Roelandt, Jens H van Dalfsen et al.
1 citation
A single 75 mg intranasal dose of ketamine reduces acute suicidal thoughts more than a 4 mg dose of the active placebo midazolam, measured 180 minutes after administration. The double-blind randomized trial includes 100 patients presenting with acute suicidality regardless of psychiatric diagnosis. The primary outcome is the change in suicidal ideation using the Beck Scale for Suicide Ideation. Secondary outcomes assess depression severity, tolerability, and biological markers. The study design addresses patient selection, ketamine formulation, clinical management, and follow-up timing.
Journal of psychiatric research
June 12, 2026
Juliana Lima Constantino, Tobias Stephan Freimann, Jens H van Dalfsen et al.
Oral esketamine can be an effective and well-tolerated treatment for treatment-resistant depression (TRD), but about half of those treated do not respond. This study tested whether sociodemographic and clinical features, including depressive symptoms and treatment resistance, could predict how much depressive symptoms would improve in 131 TRD patients receiving individually adjusted oral esketamine doses (0.5 mg/kg to 3 mg/kg) twice weekly for six weeks. Machine learning models—linear regression, elastic net, and random forest—failed to predict symptom change above chance. The findings suggest that oral esketamine may work similarly across the TRD population, regardless of treatment-resistance levels.
The pharmacogenomics journal
April 24, 2026
Daniël T Coerts, Sanne Y Smith-Apeldoorn, Jérôme C Oude Nijhuis et al.
A genetic variation in the CYP2B6 enzyme, known as 516 G > T, is linked to higher blood levels of oral esketamine four hours after dosing in people with treatment-resistant depression. In a small sample of 18 participants from a placebo-controlled trial, carriers of the variant had median esketamine levels of 5.1 µg/L, compared to 2.1 µg/L in non-carriers. No significant associations were found for two other genetic variants, CYP3A4*22 and CYP3A5*3, but the numbers of carriers were very small. Larger studies are needed to clarify their effects.