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

Ketamine

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.

Intervention / Treatment

  • Ketamine (DRUG)
    0.5 mg/kg over 40 minutes, intravenous.
  • Normal saline (placebo) (DRUG)
    Normal saline infusion over 40 minutes, equivalent volume to ketamine infusion.

Condition or Disease

  • Major Depressive Disorder
  • Surgery
  • Orthopedic Disorder

Phase

  • Phase 4

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 18 Years to 80 Years
    Enrollment: 45 (ACTUAL)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    Masking is for double blind phase only.

    QUADRUPLE:
    • Participant
    • Care Provider
    • Investigator
    • Outcomes Assessor

    Clinical Trial Dates

    Start date: Aug 22, 2019 ACTUAL
    Primary Completion: Sep 22, 2022 ACTUAL
    Completion Date: Sep 27, 2022 ACTUAL
    Study First Posted: Mar 05, 2019 ACTUAL
    Results First Posted: Aug 31, 2020
    Last Updated: Sep 27, 2022

    Sponsors / Collaborators

    Lead Sponsor: Stanford University
    Responsible Party: N/A

    Location

    Stanford, California, USA

    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.

    Participant Groups

    • Patients will receive an intravenous ketamine infusion during surgery.

    • Patients will receive an intravenous ketamine infusion during surgery.

    • Participants will receive placebo (normal saline infusion) during surgery.

    Eligibility Criteria

    Sex: All
    Minimum Age: 18
    Maximum Age: 80
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

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

    Exclusion Criteria:

    * Pregnant of breastfeeding women

    Primary Outcomes

    • This outcome measures symptoms of depression on a scales that ranges 0 to 60. A lower score indicates lower severity of symptoms. The assessment for this outcome measure will be taken once daily on days 1, 2 and 3 post procedure. A mixed model for repeated measures (MMRM) will be used to analyze the difference in postoperative MADRS score compared to pre-procedure.

    Secondary Outcomes
    • Proportion of participants with clinical response (defined as >-50% reduction in MADRS score from baseline) 1 to 3 days post procedure (up to 20 minutes to complete survey)
    Other Outcomes
    • score on Montgomery-Asberg Depression Rating Scale (MADRS) Days 5, 7 and 14 days post procedure compared to pre-procedure

    • This outcome measures self-reported symptoms of anxiety and depression on a scale that ranges from 0-42. A lower score indicates lower severity of symptoms.

    • This outcome measures average pain at the surgical site as reported by the patient on a scale of 0-10, with lower scores corresponding to less pain ("0" = no pain) and higher scores corresponding to more pain.

    • 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

    • Number of days from admission (day of surgery) through discharge after surgery.

    • This self reported outcome measure the extent to which postoperative pain interferes with typical functioning in seven domains, each rated on a scale from 0 (does not interfere) to 10 (completely interferes)

    • Proportion of participants with remission (defined as a MADRS score of <=12 on day 14) up to 14 days post procedure (up to 20 minutes to complete survey)

    More Details

    NCT Number: NCT03861988
    Other IDs: 49114
    Study URL: https://clinicaltrials.gov/study/NCT03861988
    Last updated: Sep 29, 2023