A single dose of 0.25 mg/kg esketamine given during breast cancer surgery did not significantly increase the proportion of women who achieved a 50% reduction in depression scores within three days after surgery. Among 104 women with preoperative depressive symptoms, 27% in the esketamine group reached this threshold versus 13% in the placebo group, a difference that was not statistically significant. However, esketamine did produce significantly lower depression scores on postoperative days one through five, with a mean additional decrease of 2.5 points on the Montgomery-Åsberg scale compared to placebo. No significant effects were seen on anxiety, pain, or adverse events.
A planned trial will test whether a low dose of the anesthetic esketamine, given before and during surgery, reduces depressive symptoms in women with breast cancer who are undergoing radical mastectomy. The study will randomly assign 108 women with mild-to-severe depression to receive either esketamine or a saline placebo. The main outcome is the proportion of patients whose depressive symptoms improve by the third day after surgery. The study also will measure changes in a brain protein called brain-derived neurotrophic factor and in resting-state brain connectivity, aiming to uncover how esketamine might work.
In breast cancer patients, a single preoperative dose of esketamine produced a greater reduction in depressive symptoms 24 hours after surgery compared to placebo, as measured by the Montgomery-Åsberg Depression Rating Scale. The antidepressant effect was associated with increased functional connectivity in the left superior frontal gyrus and changes in brain network properties, including reduced clustering coefficient and increased global efficiency in the default mode network. Baseline functional connectivity in the left superior frontal gyrus predicted the magnitude of the antidepressant response. The findings suggest that esketamine's rapid antidepressant action involves modulation of brain functional networks.