Ketamine Alleviates Perioperative Depression in Patients Undergoing Intracranial Tumor Resection: A Randomized Controlled Trial

Abstract

Background: Depressive symptoms occurs more than 40% in neurosurgery. However, no effective measures proved to resolve depression within the increasingly decreased hospital stay. Methods: PASSION was a single-center, randomized, placebo-controlled and double-blinded trial recruited patients from 2017 to 2018 in Beijing Tiantan Hospital, Capital Medical University. Eligible patients were 18 to 65 years old and having elective surgical resection of brain tumor with moderate-to-severe depression. Participants were randomized to receive 1 of 2 treatments: (1) the dosage of 0·5 mg/kg ketamine i.v at dura opened at the speed of 0·75 ml·kg-1·h-1 or (2) the identical volume of normal saline. Outcomes: A total of 84 patients completed the trial, of whom 41 (48·8%) randomly received ketamine and 43 (51·2%) received placebo. The primary outcome of response rate were dramatically increased by ketamine compared with placebo group (17[41·5%] vs 7[16·3%]; risk ratio, 2·55; 95% CI 1·18 to 5·50; p=0·010) at 3 days after surgery. Further, response rate at 2 days (relative risk, 2·10; 95% CI 1·07 to 4·12; p=0·024) and remission rate at discharge (relative risk, 4·20; 95% CI 1·28 to 13·80; p=0·007) were both improved by ketamine compared with placebo. No major adverse event was reported for either group. Interpretation: This trial showed that intraoperatively administered ketamine can dramatically alleviate depressive symptoms in depressive patients undergoing neurosurgery without any psychiatric side effects. These results suggest that ketamine quickly, effectively and safely eases depression, especially within one-week stay in hospital. Trial Registration: www.ClinicalTrial.gov (Identifier: NCT03086148) Funding Statement: This trial is funded by Beijing Municipal Administration of Hospitals Clinical Medical Development of Special Funding Support (code number: ZYLX201708) and Beijing Municipal Science and Technology Commission (code number: D131100005313011). Declaration of Interests: The authors declare no competing interests in this trial. Ethics Approval Statement: The study was approved by local ethics committee and all patients or their legal representatives provided written informed consent. This study followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.