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 Psychopharmacology
September 12, 2025
Stephan Tap, Kelan Thomas, Tomáš Páleníček et al.
5 citations
Classic psychedelics like psilocybin are being studied for psychiatric disorders. Current protocols typically require patients to stop antidepressants (ADs) for at least two weeks before psychedelic use to avoid serotonin syndrome and preserve efficacy, but discontinuation can worsen depression and increase suicidal ideation. This scoping review of 18 studies found that using ADs alongside classic psychedelics is generally safe and tolerable, with no increased risk of serotonin syndrome, especially with psilocybin. Some studies showed significant improvements in depression and other symptoms. Although some evidence suggests a potential reduction in acute subjective psychedelic effects, this was not consistent. The authors conclude that maintaining ADs may improve patient access and avoid discontinuation risks.
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.
Psychedelics
June 28, 2026
Joost J. Breeksema, Ulf Bremberg, Jens H van Dalfsen et al.
Psychedelic therapies face layered complexity from interactions between pharmacological and extra-pharmacological factors, and their embeddedness in societal, legal, and regulatory systems. This is compounded by epistemic fragmentation: dominant biomedical paradigms often clash with knowledge from social sciences, humanities, or Indigenous traditions. Though interdisciplinary engagement is increasingly recognized as necessary, existing calls rarely specify structural or pedagogical conditions for operationalizing it. Addressing these complexities requires moving beyond superficial collaboration; genuine interdisciplinary progress needs researchers capable of productive friction across epistemic cultures. The authors propose cultivating T-shaped competencies and intersectoral training as a structural response to these systemic challenges.
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.
Pharmacogenomics
December 12, 2025
Jérôme C Oude Nijhuis, Daniël T Coerts, Jens H van Dalfsen et al.
Oral esketamine is a promising treatment for depression that does not respond to other therapies, but how much of the drug reaches the bloodstream varies from person to person. This study tested whether common genetic variations in two drug-transport proteins, ABCB1 and ABCG2, affect esketamine levels in the blood. In 18 participants from a placebo-controlled trial, esketamine concentrations four hours after dosing did not differ significantly among people with different ABCB1 or ABCG2 genotypes. Metabolite levels also showed no association with these genetic variants. The findings suggest that these transporter polymorphisms do not influence oral esketamine pharmacokinetics, though the small sample size means the results are preliminary and need confirmation in larger studies.
Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
August 31, 2025
Cagdas Türkmen, Rutger Boesjes, Anne-Fleur Zandbergen et al.
In adults with treatment-resistant depression, intranasal esketamine added to an antidepressant does not change the likelihood of experiencing insomnia as a side effect compared with placebo. Across seven randomized trials involving 1,311 patients, insomnia was reported by 7.3% of those receiving esketamine and 6.7% of those receiving placebo, a difference that was not statistically significant. This finding contrasts with earlier reports that esketamine improves insomnia symptoms, possibly because adverse-event reporting does not capture gradual improvements in sleep for patients who often have insomnia at the start of treatment.
Journal of Affective Disorders
July 16, 2026
Sara Massetti, Sanne Y Smith-Apeldoorn, Jolien K E Veraart et al.
Ketamine and its enantiomer esketamine are effective in only 30-35% of patients with treatment-resistant depression. Increased serum brain-derived neurotrophic factor (BDNF) after a single intravenous dose has been proposed as a biomarker of antidepressant response, but effects under different treatment schedules are unclear. In a randomized, placebo-controlled trial of six-week, low-dose, oral esketamine (90 mg/day, three 30 mg intakes), depression severity and serum BDNF were measured in 54 patients at baseline, end of treatment, and after a four-week washout. BDNF levels did not significantly differ between esketamine and placebo groups during treatment or washout. An increase in BDNF occurred regardless of treatment condition.