A genetic variant in the mu-opioid receptor (OPRM1 A118G) did not alter the antidepressant response to esketamine plus an oral antidepressant in people with treatment-resistant depression. In the placebo-plus-antidepressant group, carriers of the G allele showed greater improvement in depression scores on day 2, with a similar trend at day 28, suggesting that endogenous opioids may contribute to the placebo response. No genetic effect was observed on dissociative side effects from esketamine.
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.