Preoperative Ketamine and Perioperative Depression

NCT ID: NCT04220125

Last Updated: 2023-02-06

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2023-02-02

Brief Summary

Depressive symptoms, in patients with a life history of major depressive disorder (MDD), are very common in the general population, and are especially so in elderly adults undergoing surgery.Symptoms of depression at the time of surgery is associated with risk for postoperative complications.Attenuating depressive symptoms in patients undergoing surgery is thus a plausible but not adequately tested strategy for improving patient postoperative outcomes. Conventional treatment of depression takes weeks and, therefore, is not always a realistic option, particularly when surgery is urgent. Importantly, there are currently no guidelines for diagnosing and managing MDD in surgical patients. Given its association with complications including perioperative cognitive disorders such as delirium, and over longer periods of time with dementing disorders, the feasibility and efficacy of quick-acting treatments for depressive symptoms in surgical patients are direly needed. This need is particularly acute given the rising number of elderly patients undergoing surgery who are prone to depression and surgical complications.

Aim 1: To assess the feasibility of enrolling patients in a clinical trial where a sub-anesthetic dose of ketamine (0.5 mg/kg over 40 min) or midazolam (0.045 mg/kg) is given 1 to 3 days before surgery in the preoperative clinic as a strategy to improve depressive symptoms during the perioperative period.

Aim 2: To obtain estimates of the variability in improvements of depressive symptoms (increase from baseline in MADRS score ≥ 2)1 day after surgery for patients given a sub-anesthetic dose of ketamine (0.5 mg/kg over 40 min) 1 to 3 days before surgery compared with midazolam 0.045 mg/kg.

Aim 3: To assess for the safety and tolerability of administration of a sub-anesthetic dose of ketamine (0.5 mg/kg over 40 min) given 1 to 3 days before surgery in the preoperative clinic (as an outpatient) by assessment of dysphoric symptoms or other complications including the need for hospitalization.

Hypothesis:

Aim 1: Hypothesis: Patients with preoperative depressive symptoms can be identified before surgery and successfully enrolled in a clinical trial comparing a sub-anesthetic dose of ketamine versus midazolam for improving perioperative depressive symptoms.

Aim 2: Hypothesis: Compared with midazolam, a sub-anesthetic dose of ketamine given preoperatively leads to an improvement in MADRS score ≥ 2 on day 1 after surgery.

Aim 3: Hypothesis: Compared with midazolam, a sub-anesthetic dose of ketamine is not associated with dysphoria or other complications.

Conditions

Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ketamine Group

Ketamine 0.5 mg/kg over 40 min via intravenous catheter.

Group Type: EXPERIMENTAL

Ketamine Group

Intervention Type: DRUG

Ketamine intravenous administration 0.5 mg/kg over 40 minutes.

MIdazolam Group

Midazolam 0.045 mg/kg administered via intravenous catheter.

Group Type: ACTIVE_COMPARATOR

Midazolam injection

Intervention Type: DRUG

Midazolam intravenous administration 0.045 mg/kg IV over 40 minutes.

Interventions

Ketamine Group

Ketamine intravenous administration 0.5 mg/kg over 40 minutes.

Intervention Type: DRUG

Midazolam injection

Midazolam intravenous administration 0.045 mg/kg IV over 40 minutes.

Intervention Type: DRUG

Other Intervention Names

Ketamine; Midazolam

Eligibility Criteria

Inclusion Criteria

• Male or female patients age ≥ 65 years
• Planned lumbar surgery for degenerative disc disease or spinal stenosis involving 2 or more levels
• A life history of MDD (DSM-5 criteria) and a MADRS score ≥20
• Mini-Mental State Examination (MMSE) score ≥ 15
• MMSE is between15-26
• Ability to understand English.

Exclusion Criteria

• MMSE < 15
• History of psychosis
• Poorly controlled hypertension
• Pre-existing aneurysmal vascular disorders
• Cocaine or other illicit drug use.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Charles W Hogue

Chair, Department of Anesthesiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Charles Hogue, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Other Identifiers

STU00211219

Identifier Type: -

Identifier Source: org_study_id