Over six months of routine esketamine treatment for treatment-resistant depression, depressive symptoms and daily functioning both improved progressively. By month six, 78.3% of patients showed a symptomatic response and 46.7% reached symptomatic remission, while 78.3% showed a functional response but only 33.3% achieved functional remission. Functional remission accumulated more slowly than symptomatic remission, with cumulative rates of 5% at one month, 15% at three months, and 33.3% at six months. Higher baseline disability and more previous antidepressant trials were linked to lower odds of functional remission at six months. The findings suggest that functional improvement follows a distinct trajectory from symptom improvement and should be monitored separately in treatment-resistant depression.
Treatment-resistant depression, affecting up to one third of people with major depressive disorder, often involves lasting cognitive problems that hinder recovery. A systematic review of six studies found that esketamine does not appear to cause cognitive decline in adults aged 18 to 80. Improvements in attention and processing speed were the most frequent and robust findings, seen in both randomized trials and naturalistic studies. Memory remained stable in short-term studies but improved with longer follow-up. Executive functions improved mainly in participants with baseline impairments and in long-term assessments. Overall, esketamine appears cognitively safe and may offer selective cognitive benefits, particularly in attention and processing speed, potentially supporting functional recovery.