Research Study for Major Depressive Disorder: Investigation of Glutamate Medications

Ketamine

Brief Summary

This study is examining the safety and effectiveness of two medications, ketamine and riluzole, in treating patients with treatment resistant major depressive disorder. This study will also examine the effectiveness of an FDA approved drug called lamotrigine in decreasing the potential side effects associated with ketamine.

Intervention / Treatment

  • Lamotrigine (DRUG)
    anticonvulsant medication
  • Ketamine (DRUG)
    subanesthetic dose of NMDAR antagonist
  • Riluzole (DRUG)
    glutamate release inhibitor

Condition or Disease

  • Major Depression

Phase

  • Phase 4

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 21 Years to 70 Years
    Enrollment: 26 (ACTUAL)
    Funded by: Other|NIH
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    TRIPLE:
    • Participant
    • Care Provider
    • Investigator

    Clinical Trial Dates

    Start date: Dec 01, 2006
    Primary Completion: Jul 01, 2008 ACTUAL
    Completion Date: Sep 01, 2008 ACTUAL
    Study First Posted: Jan 05, 2007 ESTIMATED
    Results First Posted: Mar 21, 2016 ESTIMATED
    Last Updated: Jul 16, 2019

    Sponsors / Collaborators

    Lead Sponsor: Baylor College of Medicine
    Responsible Party: N/A

    Location

    New York, New York, USA

    This research proposal will investigate a glutamate-modulating agent, riluzole, in treatment-resistant patients who exhibit an acute, sustained response to a single dose of intravenous (IV) racemic ketamine. Fifty ketamine-responders will be randomized to riluzole or placebo in a 4-week, randomized, double-blind, continuation-phase study.

    Participant Groups

    • Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. 300 mg of lamotrigine 2 hrs prior to ketamine infusion. Responders were randomized to one of two continuation pharmacotherapy groups, receiving either two capsules of riluzole 50 mg each (100 mg/d) or matching pill placebo under double-blind conditions.

    • 2 hours prior to ketamine infusion each patient received three capsules of placebo identical in size, weight, appearance, and taste to the lamotrigine tablets. Responders were randomized to one of two continuation pharmacotherapy groups, receiving either two capsules of riluzole 50 mg each (100 mg/d) or matching pill placebo under double-blind conditions.

    Eligibility Criteria

    Sex: All
    Minimum Age: 21
    Maximum Age: 70
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

    1. Male or female patients, 21- 70 years of age
    2. Subjects have a history of at least one previous episode of depression prior to the current episode (recurrent major depressive disorder) or have chronic major depressive disorder (at least two years' duration)
    3. Subjects have not responded to an adequate trial of one antidepressant in the current episode

    Exclusion Criteria:

    1. Female subjects who are either pregnant or nursing
    2. Serious, unstable illnesses
    3. Any previous use or treatment with ketamine, or riluzole
    4. Past intolerance to lamotrigine, including drug rash

    Primary Outcomes

    • Montgomery-Asberg Depression Rating Scale, each of the ten items can be scored from 0 (absence of symptoms to 6 most severe) and has a total score range of 0-60. A lower score on a MADRS indicates a less severe depression. The primary outcome for the initial phase of the trial was the 24-h MADRS score, which included all 10 MADRS items.

    Other Outcomes

    • Response rate and side effect differences to IV ketamine infusion based on lamotrigine and placebo pretreatment groups

    More Details

    NCT Number: NCT00419003
    Other IDs: 05-0850
    Study URL: https://clinicaltrials.gov/study/NCT00419003
    Last updated: Sep 29, 2023