Trial Outcomes & Findings for Research Study for Major Depressive Disorder: Investigation of Glutamate Medications (NCT NCT00419003)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

26 participants

Primary outcome timeframe

24 Hours

Results posted on

2019-07-31

Participant Flow

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.

2-wk psychotropic medication washout period (4 wk for fluoxetine)

Participant milestones

Participant milestones
Measure	Lamotrigine Pre-Treatment (Phase I)/Riluzole (Phase II) 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. All non responders were exited from the study. All responders (in both the lamotrigine and placebo pre-treatment groups were treated as one group and randomized into either treatment with riluzole or placebo for Phase II)	Placebo Pre-Treatment (Phase I)/Placebo (Phase II) 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. All non responders were exited from the study. All responders (in both the lamotrigine and placebo pre-treatment groups were treated as one group and randomized into either treatment with riluzole or placebo for Phase II)
Phase I, Ketamine Infusion STARTED	13	13
Phase I, Ketamine Infusion COMPLETED	7	7
Phase I, Ketamine Infusion NOT COMPLETED	6	6
Phase 2, Riluzole/Placebo Follow-Up STARTED	6	8
Phase 2, Riluzole/Placebo Follow-Up COMPLETED	5	8
Phase 2, Riluzole/Placebo Follow-Up NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Lamotrigine Pre-Treatment (Phase I)/Riluzole (Phase II) 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. All non responders were exited from the study. All responders (in both the lamotrigine and placebo pre-treatment groups were treated as one group and randomized into either treatment with riluzole or placebo for Phase II)	Placebo Pre-Treatment (Phase I)/Placebo (Phase II) 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. All non responders were exited from the study. All responders (in both the lamotrigine and placebo pre-treatment groups were treated as one group and randomized into either treatment with riluzole or placebo for Phase II)
Phase I, Ketamine Infusion Lack of Efficacy	6	6
Phase 2, Riluzole/Placebo Follow-Up Withdrawal by Subject	1	0

Baseline Characteristics

Research Study for Major Depressive Disorder: Investigation of Glutamate Medications

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lamotrigine Pre-Treatment n=13 Participants 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.	Placebo Pre-Treatment n=13 Participants 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.	Total n=26 Participants Total of all reporting groups
Age, Continuous	48.2 years STANDARD_DEVIATION 11.8 • n=5 Participants	48.2 years STANDARD_DEVIATION 11.8 • n=7 Participants	48.2 years STANDARD_DEVIATION 11.8 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants	13 participants n=7 Participants	26 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Riluzole Group n=13 Participants Patients who responded (n=14) to the ketamine infusion (in either the lamotrigine or placebo pre-treatment groups) were randomized into phase II for treatment with either riluzole or placebo. One patient in the riluzole group was discontinued/withdrew consent before completing the study.	Placebo n=13 Participants Patients who responded (n=14) to the ketamine infusion (in either the lamotrigine or placebo pre-treatment groups) were randomized into phase II for treatment with either riluzole or placebo.
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 Interval 15.9 to 33.0	22.0 scores on a scale Interval 14.9 to 29.1

OTHER_PRE_SPECIFIED outcome

Timeframe: 24, 48, or 72-hrs

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