Effect of esketamine on postoperative depression in women with breast cancer and preoperative depressive symptoms: The EASE randomized trial

Abstract

Study objective

To determine whether intraoperative low-dose esketamine ameliorates depression in women having breast cancer surgery.

Design

A prospective single-center double blind randomized placebo-controlled trial.

Setting

Perioperative period, operating room, post anesthesia care unit and hospital ward.

Patients

108 women 18–65 years old who were scheduled for elective breast cancer surgery. All had preoperative depressive symptoms as defined by Montgomery-Åsberg depression scores ≥12 (range, 0–60; higher scores indicate more severe depression).

Interventions

Eligible participants were randomized to esketamine 0.25 mg/kg or saline placebo. Blinded trial drugs were given intravenously over the initial 40 min of anesthesia.

Measurements

Our primary outcome was the fraction of patients who had at least a 50 % reduction in the Montgomery-Åsberg depression score within 3 postoperative days. Secondary outcomes included the fraction of patients with depression remission defined as Montgomery-Åsberg scores ≤10, the numeric value of the Montgomery-Åsberg depression scores, postoperative severe pain, and anxiety as determined by the Generalized Anxiety Disorder 7-item score. Adverse events were monitored for 72 postoperative hours.

Main results

54 women each were randomized to esketamine and saline, and 104 were available for our intent-to-treat analysis. The mean age was 50 years. Esketamine non-significantly doubled the fraction of patients who had a 50 % reduction in their depressions scores: 27 % vs 13 %, odds ratio 2.4, [95 % CI 0.9 to 6.6], P = 0.087. Montgomery-Åsberg depression scores were nearly a factor-of-two and significantly lower (better) on postoperative days 1 to 5 in patients given esketamine. Montgomery-Åsberg scores decreased significantly more from baseline in patients randomized to esketamine: mean difference − 2.5 [95 % CI -4.5 to −0.6], P = 0.010. Esketamine treatment had no significant effect on other secondary outcomes or on adverse events.

Conclusions

Intraoperative administration of 0.25 mg/kg esketamine did not significantly improve the fraction of depressed women having breast cancer patients who had a 50 % reduction in their depression scores at 3 days postoperatively. However, the observed factor-of-two treatment effect was clinically meaningful and esketamine significantly reduced short-term postoperative depression scores without provoking complications. Robust trials are warranted.

Registration Trial registry: http://www.chictr.org.cn/; Identifier: ChiCTR2300071062.