An open-label study of (R)-ketamine for depression cannot establish efficacy due to expectancy biases and large placebo effects, even in treatment-resistant patients. One patient showed clinically meaningful dissociation. The antidepressant efficacy and optimal dose of (R)-ketamine must be determined in randomized controlled trials. A study in healthy volunteers found that (R)-ketamine and (S)-ketamine produced similar frequency and character of dissociative and other central nervous system adverse effects when compared at doses equipotent for NMDAR antagonism.
Patients with treatment-resistant depression who also have anxiety tend to respond less well to antidepressants. This analysis of existing trial data examined whether adding esketamine to an antidepressant improves outcomes for such patients. Among those with comorbid anxiety, the combination of esketamine and an antidepressant led to greater improvement in depressive symptoms compared to an antidepressant alone. The benefit was also seen in patients without anxiety, though the difference was less pronounced. The results suggest that esketamine augmentation may be particularly helpful for treatment-resistant depression patients who also struggle with anxiety.