Major Depression
Conditions
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.
Interventions
DRUGLamotrigine
anticonvulsant medication
DRUGKetamine
subanesthetic dose of NMDAR antagonist
DRUGRiluzole
glutamate release inhibitor
Sponsors
National Alliance for Research on Schizophrenia and Depression
National Center for Research Resources (NCRR)
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Lamotrigine in Decreasing IV Ketamine Psychotomimetic Side Effects | 24, 48, or 72-hrs | Response rate and side effect differences to IV ketamine infusion based on lamotrigine and placebo pretreatment groups |
Countries
United States
Participant flow
Recruitment details
The intent-to-treat sample (n=26) was recruited from media/internet advertising (14), psychiatrist referral (8), or self-referral from the New York Mood Disorders Support Group (4). Patients had marked depressive severity, chronicity, and anxiety comorbidity, and were highly pharmacotherapy-resistant.
Pre-assignment details
2-wk psychotropic medication washout period (4 wk for fluoxetine)
Participants by arm
| Arm | Count |
|---|---|
| Lamotrigine Pre-Treatment 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. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth. | 13 |
| Placebo Pre-Treatment 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. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth. | 13 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase 2, Riluzole/Placebo Follow-Up | Withdrawal by Subject | 1 | 0 |
| Phase I, Ketamine Infusion | Lack of Efficacy | 6 | 6 |
Baseline characteristics
| Characteristic | Lamotrigine Pre-Treatment | Placebo Pre-Treatment | Total |
|---|---|---|---|
| Age, Continuous | 48.2 years STANDARD_DEVIATION 11.8 | 48.2 years STANDARD_DEVIATION 11.8 | 48.2 years STANDARD_DEVIATION 11.8 |
| Region of Enrollment United States | 13 participants | 13 participants | 26 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 5 / 8 | 26 / 26 | 5 / 13 | 0 / 13 |
| serious Total, serious adverse events | 0 / 6 | 0 / 8 | 0 / 26 | 0 / 13 | 0 / 13 |
Outcome results
Primary
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.
Time frame: 24 Hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Riluzole Group | Montgomery-Asberg Depression Rating Scale (MARDS) Score (Acute Response to IV Ketamine in Patients With Treatment Resistant Major Depression) | 24.4 scores on a scale |
| Placebo | Montgomery-Asberg Depression Rating Scale (MARDS) Score (Acute Response to IV Ketamine in Patients With Treatment Resistant Major Depression) | 22.0 scores on a scale |
Other Pre-specified
Efficacy of Lamotrigine in Decreasing IV Ketamine Psychotomimetic Side Effects
Response rate and side effect differences to IV ketamine infusion based on lamotrigine and placebo pretreatment groups
Time frame: 24, 48, or 72-hrs