Research Study for Major Depressive Disorder: Investigation of Glutamate Medications

Phase 4

Completed

• Conditions: Major Depression
• Interventions: Drug: Lamotrigine; Drug: Ketamine; Drug: Riluzole

• Registration Number: NCT00419003
• Lead Sponsor: Baylor College of Medicine

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.

Detailed Description

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.

Study Timeline

• Study Start: 2006-12
• Study First Submitted: 2007-01-04
• Study First Submitted QC: 2007-01-04
• Study First Posted: 2007-01-05
• Primary Completion: 2008-07
• Study Completion: 2008-09
• Results First Submitted: 2013-09-05
• Results First Submitted QC: 2016-02-19
• Results First Posted: 2016-03-21
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-16
• Last Update Posted: 2019-07-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Lamotrigine Pre-Treatment	Lamotrigine	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.
Lamotrigine Pre-Treatment	Ketamine	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.
Lamotrigine Pre-Treatment	Riluzole	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.
Placebo Pre-Treatment	Riluzole	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.
Placebo Pre-Treatment	Ketamine	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.

Primary Outcome Measures

Name	Time	Method
Montgomery-Asberg Depression Rating Scale (MARDS) Score (Acute Response to IV Ketamine in Patients With Treatment Resistant Major Depression)	24 Hours	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.

Trial Locations

Locations (1)

Mount Sinai School of Medicine; 🇺🇸 New York, New York, United States