Intraoperative Ketamine Versus Saline in Depressed Patients Undergoing Anesthesia for Non-cardiac Surgery

Phase 4

Completed

Conditions: Major Depressive Disorder
Surgery
Orthopedic Disorder

Interventions: Drug: Normal saline (placebo)
Drug: Ketamine

Registration Number: NCT03861988

Lead Sponsor: Stanford University

Brief Summary: This study evaluates whether ketamine, given as part of an anesthetic, improves depression symptoms in depressed patients undergoing non-cardiac surgery. Half of participants will receive a ketamine infusion during surgery, while the other half will receive a placebo (normal saline) during surgery.

Detailed Description: Major Depressive Disorder (MDD) is widely prevalent among patients preparing to have surgery, and is a known risk factor for complications after surgery, including wound infection, myocardial infarction and opioid use disorder. Ketamine has emerged as an effective, rapid-acting antidepressant therapy for patients with MDD, and may be a useful tool to prevent MDD-related morbidity in the perioperative period. Ketamine has been well studied for MDD in outpatient clinics where it is given as an infusion (0.5 mg/kg over 40 minutes) in awake patients. Ketamine is often used as part of an anesthetic cocktail in sedated or anesthetized patients, but it is unknown whether ketamine has an antidepressant effect in this context. The investigators will determine whether a ketamine infusion, compared to placebo (normal saline infusion), has an antidepressant effect when given during surgical anesthesia. If ketamine is an effective antidepressant in this population under anesthesia, its use could be incorporated into a set of interventions to minimize the perioperative complications associated with MDD.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 45

Inclusion Criteria

Patient presenting for non-cardiac, non-intracranial surgery
Major Depressive Disorder

Exclusion Criteria

Pregnant of breastfeeding women

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Double blind placebo	Normal saline (placebo)	Participants will receive placebo (normal saline infusion) during surgery.
Open label ketamine	Ketamine	Patients will receive an intravenous ketamine infusion during surgery.
Double blind ketamine	Ketamine	Patients will receive an intravenous ketamine infusion during surgery.

Primary Outcome Measures

Name	Time	Method
Montgomery-Asberg Depression Rating Scale (MADRS) Score	Post-intervention days 1, 2 and 3	The MADRS is a 10-item scale for the evaluation of depressive symptoms (Montgomery et al 1979). Each MADRS item is rated on a 0 to 6 scale. Total score range from 0-60, where lower MADRS scores indicate lower levels of depressive symptoms. The assessment for this outcome will be taken once daily on days 1, 2 and 3 post procedure. A mixed model for repeated measures (MMRM) was used to analyze the difference in postoperative MADRS score between ketamine and placebo groups..

Secondary Outcome Measures

Name	Time	Method
Hospital Length of Stay	Average approximately 3 days post-intervention	Number of days from admission (day of surgery) through discharge after surgery.
Number of Participants With Clinical Response	Post-intervention days 1, 2 and 3	Clinical response defined as \>=50% reduction in MADRS score from baseline. MADRS score range: 0 to 60, a lower score indicates lower severity of symptoms.
Number of Participants With Remission	Post-intervention day 14	Remission defined as a MADRS score of \<=12 on day 14. MADRS score range: 0 to 60, a lower score indicates lower severity of symptoms.
Hospital Anxiety and Depression Scale (HADS) Scale Score	Post-intervention days 1, 2, 3, 5, 7 and 14	This outcome measures self-reported symptoms of anxiety and depression on a scale that ranges from 0 to 42. A lower score indicates lower severity of symptoms.
Cumulative Opioid Use	Post-intervention days 1, 2, 3, 5, 7 and 14	This outcome measures how many cumulative morphine-equivalents milligrams of opioid pain medication the patient has taken as an inpatient and after discharge from hospital
Brief Pain Inventory Pain Intensity Scale Score	Post-intervention days 1, 2, 3, 5, 7 and 14	Average pain intensity in the past 24 hours, rated on a numerical scale from 0 to 10 (with 0 representing "No pain" and 10 representing "Pain as bad as you can imagine").
Brief Pain Inventory Pain Interference Scale Score	Post-intervention days 1, 2, 3, 5, 7 and 14	Pain interference in the past 24 hours, rated on a numerical scale from 0 to 10 (with 0 representing "Does not interfere" and 10 representing "Completely interferes").