Effect of esketamine on perioperative depressive symptoms in major surgery patients (PASSION II): study protocol for a randomised controlled trial

Abstract

IntroductionDepressive symptoms are common for patients undergoing major surgery and may worsen their mental health and lead to poor clinical outcomes. It is essential to seek a safe rapid-acting treatment for relieving moderate-to-severe depressive symptoms in patients undergoing major surgery.Methods and analysisThis study is a randomised, placebo-controlled and double-blinded trial aiming to determine the effect of esketamine on moderate-to-severe depressive symptoms in patients undergoing major surgery. Five hundred and sixty-four participants, aged 18–65 years old, undergoing major surgery will be randomly allocated into the esketamine and placebo groups at a 1:1 ratio. Esketamine or placebo will be given intravenously at the same speed on suturing the incision by anaesthesiologists in charge who are blinded to the randomisation. In the esketamine group, the total dosage of esketamine will be 0.2 mg/kg body weight. To estimate the efficacy and safety endpoints, blinded evaluation by trained researchers will be completed at 3 days, 5 days, 1 month, 3 months and 6 months after surgery. The primary outcome is the remission rate at the third postoperative day. The secondary outcomes include depression-related scores, severe pain events and safety-related endpoints such as psychotic symptoms, manic symptoms and dissociative symptoms.Ethics and disseminationThis study was approved by the Institutional Review Board of Beijing Tiantan Hospital, Capital Medical University, Beijing, China on 30 October 2020 (KY-2020-058-02). This trial is designed to explore whether the administration of esketamine could improve the mental health of patients with depressive symptoms undergoing major surgery. The conclusions of this study will be published in peer-reviewed journals.Trial registration numberNCT04425473.