Research Study for Major Depressive Disorder: Investigation of Glutamate Medications

Baylor College of Medicine

Status and phase: Completed; Phase 4

Conditions: Major Depression

Treatments: Drug: Lamotrigine; Drug: Riluzole; Drug: Ketamine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00419003

05-0850

5M01RR000071-46 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 26 patients

Sex: All

Ages: 21 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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26 participants in 2 patient groups, including a placebo group

Lamotrigine Pre-Treatment

Experimental group

Description:

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.

Treatment:

Drug: Ketamine

Drug: Riluzole

Drug: Lamotrigine

Placebo Pre-Treatment

Placebo Comparator group

Description:

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.

Treatment:

Drug: Ketamine

Drug: Riluzole