Preoperative Ketamine and Perioperative Depression
Status:
Not yet recruiting
Trial end date:
2023-09-01
Target enrollment:
Participant gender:
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.