Journal Article Annotations
2024, 2nd Quarter

Pain

Annotations by Alissa Hutto, MD
July, 2024

Effects of a single subanesthetic dose of esketamine on postoperative subthreshold depressive symptoms in patients undergoing unilateral modified radical mastectomy: a randomised, controlled, double-blind trial.

PUBLICATION #1 — Pain

Effects of a single subanesthetic dose of esketamine on postoperative subthreshold depressive symptoms in patients undergoing unilateral modified radical mastectomy: a randomised, controlled, double-blind trial.

Huanwei Wang, Rigen Te, Jianxing Zhang, Yanbing Su, Hongxia Zhou, Na Guo, Dongmei Chi, Wan Huang.

Abstract: Randomized Controlled Trial BMC Psychiatry. 2024 Apr 24;24(1):315. doi: 10.1186/s12888-024-05753-9.

Background:
Breast cancer is the most common malignant tumor in females worldwide. During disease development, breast cancer patients suffer anxious and depressed, which may lead to worse quality of life or even higher mortality. Esketamine has been regarded as an antidepressant in breast cancer patients with mild or moderate depression. Here, we wonder whether the administration of esketamine could reduce the postoperative depressive symptom score of breast cancer patients who have no preoperative depression.

Methods:
A total of 64 patients treated with unilateral modified radical mastectomy were randomly divided into an experimental group (esketamine group, Group E) and a control group (Group C), with 32 cases in each one. After anesthesia induction, Group C received 0.2 ml/kg of normal saline intravenously and Group E was administered 0.2 mg/kg intravenous esketamine. The primary outcome was the Patient Health Questionnaire-9 (PHQ-9) scores. The secondary outcomes included the Visual Analogue Scale (VAS) scores for pain, inflammatory markers, perioperative-related indicators, and the incidence of postoperative delirium, nausea and vomiting.

Results:
The PHQ-9 score on postoperative day (POD) 1 in Group E declined from the preoperative level, while the score in Group C was higher than before, and the former was far lower than the latter (P = 0.047). There is no statistically significant difference in PHQ-9 scores between Group E and Group C on POD 3, 7, and 30. Moreover, the postoperative leukocyte level of Group E was higher than that of Group C, and the difference was statistically significant (P = 0.030).

Conclusions:
A single subanesthetic dose of esketamine can result in lower postoperative score on subthreshold depressive symptoms compared to the Group C on POD 1, without increasing the occurrence of postoperative adverse reactions.

Annotation

The finding:
In a double-blind RCT, one dose of esketamine 0.2 mg/kg IV was compared to the same dose of normal saline given intraoperatively to people getting a unilateral modified radical mastectomy. Primary outcomes were PHQ-9 and VAS (visual analogue scale) scores, and only post-operative day 1 (POD1) PHQ-9 score was found to be significantly reduced in the esketamine group. Among secondary outcomes, white blood cell count was found to be significantly elevated in the esketamine group; there was no difference in measured subjective patient experience.

Strength and weaknesses:
There was a 2023 meta-analysis by Guo et al about perioperative administration of ketamine that involved similarly-modelled studies, and this team used the same outcome measures, which helps for future comparison. The study was straightforward with well-displayed results, but the level of simplicity made some details vague. It is unclear if all of these breast cancer patients were female, and there is no data on socioeconomic status or education. They explicitly chose people who did not have pre-operative depression or any other mental health diagnosis, so generalization is poor especially in the population seen by the CL psychiatrist. While they report significantly lower PHQ-9 on POD1 for the esketamine group, the difference in PHQ-9 score from pre-op to POD1 was 1.03 points; clinical relevance is of this effect is likely negligible. Additionally, the short intervals of repeat PHQ-9s, which prompts patient to reply based on the past 2 weeks, makes it hard to interpret the differences between timepoints. Overall, perhaps the most useful finding is the tolerability of the esketamine compared to control.

Relevance:
As ketamine and esketamine continue to be more accessible as psychiatric and pain management treatments, it will be important for CL psychiatrists to remain informed about the possible uses and benefits of these medications for hospitalized patients and the differences between the two enantiomers. Additionally, CL psychiatrists could be asked to weigh in on selecting these agents as part of anesthesia/periop care, and continued research on their efficacy and safety will help guide any recommendations.