Research Study for Major Depressive Disorder: Investigation of Glutamate Medications

Study Overview
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Brief Summary
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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
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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.

Official Title
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Continuation Riluzole in the Prevention of Relapse Following Ketamine in Major Depression

Conditions
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Major Depression

Intervention / Treatment
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* Drug: Lamotrigine
* Drug: Ketamine
* Drug: Riluzole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients, 21- 70 years of age 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) Subjects have not responded to an adequate trial of one antidepressant in the current episode Exclusion Criteria: Female subjects who are either pregnant or nursing Serious, unstable illnesses Any previous use or treatment with ketamine, or riluzole Past intolerance to lamotrigine, including drug rash

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lamotrigine Pre-Treatment<br>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. | Drug: Lamotrigine<br>* anticonvulsant medication<br>* Other names: lamictal;Drug: Ketamine<br>* subanesthetic dose of NMDAR antagonist<br>* Other names: ketalar;Drug: Riluzole<br>* glutamate release inhibitor<br>* Other names: rilutek;|
| Placebo Comparator: Placebo Pre-Treatment<br>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. | Drug: Ketamine<br>* subanesthetic dose of NMDAR antagonist<br>* Other names: ketalar;Drug: Riluzole<br>* glutamate release inhibitor<br>* Other names: rilutek;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale (MARDS) Score (Acute Response to IV Ketamine in Patients With Treatment Resistant Major Depression) | 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. | 24 Hours |