CNS drugs
August 1, 2024
Liliana Patarroyo-Rodriguez, Stefanie Cavalcanti, Jennifer L Vande Voort et al.
13 citations
Anhedonia, the inability to feel pleasure, is a symptom that appears in many mental disorders beyond just depression and schizophrenia, and it is linked to worse outcomes such as higher suicide risk and poor treatment response. Although brain imaging and biomarkers have improved understanding, the neural basis of anhedonia is still not fully known. Ketamine, a fast-acting antidepressant, also seems to reduce anhedonia through a separate mechanism from its antidepressant effects. Other potential treatments are being explored, but many questions remain, highlighting the need for more research.
Therapeutic advances in psychopharmacology
January 1, 2025
Ahmed Elmosalamy, Idil Tarikogullari, Liliana Patarroyo-Rodriguez et al.
7 citations
About one-third of people with depression do not respond to standard treatments, a condition known as treatment-resistant depression (TRD). Intravenous (IV) ketamine and esketamine (given IV or as a nasal spray) are newer options for TRD, but only the nasal spray version of esketamine is FDA-approved. A meta-analysis of eight studies with 978 adults directly comparing IV ketamine with esketamine found that both treatments produced similar rates of response and remission after acute treatment, with a slight but not statistically significant advantage for IV ketamine. IV ketamine may work faster, but the evidence is mostly from observational studies, and large randomized trials are needed to confirm these findings.
Journal of affective disorders
September 15, 2025
Brandan K Penaluna, Jennifer L Vande Voort, William V Bobo et al.
4 citations
In people with treatment-resistant depression, intravenous ketamine improved symptoms across four depression subtypes: Sadness, Negative Thoughts, detachment/Interest and Activity, and Neurovegetative. After three infusions over 11 days, 53% of the 75 participants achieved remission. The Negative Thoughts subtype showed the least improvement, and the Neurovegetative subtype was the least responsive overall. Higher baseline Sadness scores were linked to lower remission rates, and a positive Sadness phenotype reduced the odds of remission (odds ratio 0.32). No meaningful sex differences in response were found by the end of treatment.
Journal of affective disorders
August 15, 2025
Stefanie Cavalcanti, Vanessa K Pazdernik, Jennifer L Vande Voort et al.
3 citations
Among adults with treatment-resistant depression receiving ketamine or esketamine, those reporting high perceived stress before treatment had lower odds of remission and needed more treatment sessions to achieve remission. In a cohort of 39 patients, 66.7% had high perceived stress. Each 5-point increase on the Perceived Stress Scale reduced the odds of remission by 60%, independent of baseline depression severity. Patients with high stress required a median of 3 treatments to reach remission versus 1 for those with low-to-moderate stress. The observational design and lack of a placebo group limit the findings.
The Journal of clinical psychiatry
January 21, 2026
Matheus G Marques, Aysegul Özerdem, Simon Kung et al.
1 citation
For treatment-resistant depression (TRD), a panel of 10 psychiatrists reached strong consensus on recommending augmentation with second-generation antipsychotics, transcranial magnetic stimulation, and ketamine/esketamine as next-step treatments after three failed antidepressant trials. Treatment preferences shifted to include nonaugmentative antidepressants and electroconvulsive therapy depending on patient characteristics such as metabolic disease and age. The findings underscore the importance of tailoring TRD treatment strategies to individual patient factors beyond conventional guideline tiers.
Biological psychiatry global open science
July 1, 2025
Stephen A Murata, Zachary B Madaj, Colt D Capan et al.
1 citation
Higher baseline levels of anthranilic acid (AA), a metabolite in the kynurenine pathway, predicted remission in patients with treatment-resistant depression receiving intravenous ketamine. In an open-label trial of 74 patients, 52% achieved remission after three infusions. Composite ratios of AA to intercellular adhesion molecule-1 and AA to tryptophan improved predictive accuracy over AA alone. The findings suggest that immunometabolic biomarkers could guide personalized ketamine treatment.