Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies

Guo, Jie; Qiu, Di; Gu, Hanwen; Wang, Xingming; Hashimoto, Kenji; Zhang, Guang-Fen; Yang, Jianjun

doi:10.1038/s41380-023-01945-z

Cited by 15 publications

(12 citation statements)

References 66 publications

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“…Other studies have also evaluated the effect of ketamine on mood ratings in surgical patients 46 ; however, numerous methodological limitations prevent direct comparison to studies of intravenous ketamine for depression in the psychiatric literature. Frequently, these trials were not conducted in a population likely to meet criteria for moderate-to-severe MDD 47-51 .…”

Section: Discussionmentioning

confidence: 99%

Randomized Trial of Ketamine Masked by Surgical Anesthesia in Depressed Patients

Lii

Smith

Flohr

et al. 2023

Preprint

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BACKGROUND Ketamine may have antidepressant properties, but its acute psychoactive effects complicate successful masking in placebo-controlled trials. METHODS In a triple-masked, randomized, placebo-controlled trial, 40 adult patients with major depressive disorder were randomized to a single infusion of ketamine (0.5 mg/kg) or placebo (saline) during anesthesia for routine surgery. The primary outcome was depression severity measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at 1, 2, and 3 days post-infusion. The secondary outcome was the proportion of participants with clinical response (≥50% reduction in MADRS scores) at 1, 2, and 3 days post-infusion. After all follow-up visits, participants were asked to guess which intervention they received. RESULTS Mean MADRS scores did not differ between groups at screening or pre-infusion baseline. The mixed-effects model showed no evidence of effect of group assignment on post-infusion MADRS scores at 1 to 3 days post-infusion (-5.82, 95% CI -13.3 to 1.64, p=0.13). Clinical response rates were similar between groups (60% versus 50% on day 1) and comparable to previous studies of ketamine in depressed populations. Secondary and exploratory outcomes found no evidence of benefit for ketamine. 36.8% of participants guessed their treatment assignment correctly; both groups allocated their guesses in similar proportions. CONCLUSION A single dose of intravenous ketamine compared to placebo has no short-term effect on the severity of depression symptoms in adults with major depressive disorder. This trial successfully masked treatment allocation in moderate-to-severely depressed patients using surgical anesthesia. While it is impractical to use surgical anesthesia for most placebo-controlled trials, future studies of novel antidepressants with acute psychoactive effects should make efforts to fully mask treatment assignment in order to minimize subject-expectancy bias. (ClinicalTrials.gov number,NCT03861988)

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Section: Discussionmentioning

confidence: 99%

Randomized Trial of Ketamine Masked by Surgical Anesthesia in Depressed Patients

Lii

Smith

Flohr

et al. 2023

Preprint

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“…Epidural analgesia will be employed for postoperative pain control, and the commencement time of surgery will be recorded. A prior meta-analysis has indicated that ketamine may ameliorate postoperative depression 24. However, in the study by Qiu et al ,3 no significant differences were observed in depression scores between the two groups during the follow-up period.…”

Section: Discussionmentioning

confidence: 90%

Efficacy of epidural esketamine on postoperative sleep quality after laparoscopic and robotic lower abdominal surgeries: a study protocol for randomised, double-blind, controlled trial

Yang,

Zhang,

Zhou

et al. 2024

BMJ Open

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IntroductionPostoperative sleep disturbances significantly impair postoperative recovery. The administration of intravenous esketamine has been shown to potentially improve postoperative sleep quality. However, the effectiveness of epidural esketamine in improving postoperative sleep quality remains to be elucidated. This study aims to explore the impact of both intraoperative and postoperative use of epidural esketamine on the postoperative sleep quality of patients undergoing minimally invasive lower abdominal surgeries.Methods and analysisThis randomised, double-blind, parallel-group, placebo-controlled trial will be conducted at the Fudan University Shanghai Cancer Centre. A total of 128 adults undergoing minimally invasive lower abdominal surgeries will be randomly allocated in a 1:1 ratio to either the esketamine group or the placebo group. In the esketamine group, epidural esketamine will be administered intraoperatively (0.2 mg/kg) and postoperatively (25 mg). Postoperatively, all patients will receive epidural analgesia. The primary outcome of the study is the incidence of poor sleep quality on the third day after surgery. The sleep quality assessment will be conducted using the Pittsburgh Sleep Quality Index and a Numeric Rating Scale of sleep. The main secondary outcomes include postoperative pain and anxiety and depression scores. The postoperative pain, both rest pain and movement pain, will be assessed using a Numerical Rating Scale within 5 days after surgery. Anxiety and depression scores will be evaluated using the Hospital Anxiety and Depression Scale both before and after the surgery. Safety outcomes will include delirium, fidgeting, hallucinations, dizziness and nightmares. The analyses will be performed in accordance with intention-to-treat principleEthics and disseminationEthics approval has been obtained from the Ethics Committee of the Shanghai Cancer Centre (2309281-9). Prior to participation, all patients will provide written informed consent. The results of the trial are intended to be published in a peer-reviewed journal.Trial registration numberChiCTR2300076862.

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“…In terms of adverse effects, recent studies found that esketamine did not significantly increase the risk for nausea, vomiting, and psychotomimetic adverse events ( 12 , 15 ). On the other hand, a recent meta-analysis showed that perioperative use of ketamine reduced postoperative depression scores, but increased the risk of adverse effects including nausea and vomiting, headache, dizziness, and hallucination ( 14 ). In our study, the most commonly reported adverse events were mild PONV and dizziness, and the rates were similar between groups.…”

Section: Discussionmentioning

confidence: 99%

“…Preclinical studies suggested that those side effects of ketamine may be attributed to S-ketamine, but not R-ketamine ( 7 , 13 ). However, recent clinical evidence showed that perioperative use of ketamine increased the risk of psychotomimetic adverse events ( 14 ), while esketamine did not significantly increase the risk ( 12 , 15 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of esketamine on postoperative depressive symptoms in patients undergoing thoracoscopic lung cancer surgery: A randomized controlled trial

et al. 2023

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BackgroundDepressive symptoms are common among patients with lung cancer. We aimed to assess the effects of esketamine on postoperative depressive symptoms after thoracoscopic lung cancer surgery.MethodsIn this randomized, double-blind, placebo-controlled trial, 156 patients undergoing thoracoscopic lung cancer surgery were randomly allocated in a 1:1 ratio to receive intravenous esketamine (intraoperatively and in patient-controlled analgesia until 48 h postoperatively) or normal saline placebo. The primary outcome was the proportion of patients with depressive symptoms at 1 month postoperatively, assessed using the Beck Depression Inventory-II (BDI-II). Secondary outcomes included depressive symptoms at 48 h postoperatively, hospital discharge and 3 months postoperatively, BDI-II scores, anxious symptoms, Beck Anxiety Inventory scores, Quality of Recovery-15 (QoR-15) scores, and 1- and 3-month mortality.Main resultsA total of 151 patients (75 in the esketamine group and 76 in the normal saline group) completed the 1-month follow-up. The esketamine group had a significantly lower incidence of depressive symptoms at 1 month compared to the normal saline group (1.3% vs. 11.8%; risk difference = −10.5, 95%CI = −19.6% to −0.49%; p = 0.018). After excluding patients without lung cancer diagnosis, the incidence of depressive symptoms was also lower in the esketamine group (1.4% vs. 12.2%; risk difference = −10.8, 95%CI = −20.2% to −0.52%; p = 0.018). The secondary outcomes were similar between groups, except that the esketamine group had higher QoR-15 scores at 1 month postoperatively (median difference = 2; 95%CI = 0 to 5; p = 0.048). The independent risk factors for depressive symptoms were hypertension (odds ratio = 6.75, 95%CI = 1.13 to 40.31; p = 0.036) and preoperative anxious symptoms (odds ratio = 23.83, 95%CI = 3.41 to 166.33; p = 0.001).ConclusionPerioperative administration of esketamine reduced the incidence of depressive symptoms at 1 month after thoracoscopic lung cancer surgery. History of hypertension and preoperative anxious symptoms were independent risk factors for depressive symptoms.Clinical trial registration: Chinese Clinical Trial Registry http://www.chictr.org.cn, Identifier (ChiCTR2100046194).

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Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies

Cited by 15 publications

References 66 publications

Randomized Trial of Ketamine Masked by Surgical Anesthesia in Depressed Patients

Randomized Trial of Ketamine Masked by Surgical Anesthesia in Depressed Patients

Efficacy of epidural esketamine on postoperative sleep quality after laparoscopic and robotic lower abdominal surgeries: a study protocol for randomised, double-blind, controlled trial

Effect of esketamine on postoperative depressive symptoms in patients undergoing thoracoscopic lung cancer surgery: A randomized controlled trial

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