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.
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.