Major Depressive Disorder
Conditions
Keywords
Major Depression, Major Depressive Disorder, Depression, Riluzole, Glutamate, Sertraline
Brief summary
The investigators are doing a research study to find out if riluzole, when taken along with a standard antidepressant (sertraline) can help people with major depression. This research study will compare riluzole + sertraline to placebo + sertraline. The investigators hypothesize that adding riluzole will lead to a better antidepressant response, in less time, then sertraline alone.
Detailed description
Recent attention has focused on the glutamatergic system as a new, distinct target for depression treatment. Riluzole (Rilutek, Sanofi), an oral modulator of glutamate activity with neuroprotective and anticonvulsant properties, is currently approved by the United States Food and Drug Administration for treatment of amyotrophic lateral sclerosis (ALS). Preliminary studies using riluzole to treat depression in humans are promising, though larger, double-blinded controlled trials are needed. Overall study population: Adult outpatients with a current, untreated major depressive episode. Disallowed therapies include: other psychotropic medications, including antipsychotics, mood stabilizers, benzodiazepines, barbiturates, other sedative-hypnotics, chronic opiates, or additional antidepressants, psychotherapy, electroconvulsive therapy, vagal nerve stimulations therapy, transcranial magnetic stimulation therapy, or phototherapy.
Interventions
DRUGRiluzole
DRUGSertraline
OTHERplacebo
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Adults (ages 18-75) who meet DSM-IV criteria for a major depressive episode, * Hamilton Depression Rating Scale (HDRS) \>22, and * No antidepressant treatment for at least three weeks
Exclusion criteria
* Active drug or alcohol disorder in the past 3 months * History of psychosis, history of mania or hypomania * Epilepsy or history of seizures * Hypothyroidism * Congenital QTc prolongation * Liver disease * Lung disease * Acute suicide or homicide risk * Pregnant women, breastfeeding women, women of childbearing age not using contraception * Unstable medical illness * Elevated thyroid-stimulating hormone (TSH\>5.0mlU/L), or * Abnormal liver function tests (ALT\>50 U/L or AST\>50 U/L) * ADD / ADHD (Attention deficit hyperactivity disorder) Disallowed therapies include: other psychotropic medications, including antipsychotics, mood stabilizers, benzodiazepines, barbiturates, other sedative-hypnotics, chronic opiates, or additional antidepressants, psychotherapy, electroconvulsive therapy, vagal nerve stimulations therapy, transcranial magnetic stimulation therapy, or phototherapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Experiencing an Antidepressant Response (>50% Reduction in HDRS) at Endpoint of 8 Weeks | 0 weeks-8 weeks | The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52. |
| Mean Change in Hamilton Depression Rating Scale (HDRS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks | 0 weeks-8 weeks | The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52. |
| Number of Patients Experiencing Remission From Depression (HDRS<7) at Endpoint of 8 Weeks | 0 weeks-8 weeks | The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Hamilton Anxiety Rating Scale (HARS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks | 0 weeks-8 weeks | The HARS scale is a clinician rated interview scale designed to measure the signs and symptoms of anxiety. It has 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicate less anxiety. |
| Mean Change in Clinical Global Impression (CGI) Scale From Baseline (0 Weeks) to Endpoint at 8 Weeks | 0 weeks-8 weeks | The Clinical Global Impression Scale (CGI) is a brief clinician-rated instrument. The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Treatment response ratings should take account of both therapeutic efficacy and treatment-related adverse events and range from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sertraline + Riluzole sertraline 100 mg po daily and riluzole 50 mg po bid
Riluzole
Sertraline | 6 |
| Sertraline + Placebo sertraline 100 mg po daily and placebo
Sertraline
placebo | 7 |
| Total | 13 |
Baseline characteristics
| Characteristic | Sertraline + Placebo | Sertraline + Riluzole | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 5 Participants | 12 Participants |
| Age, Continuous | 52.86 years STANDARD_DEVIATION 7.71 | 53.83 years STANDARD_DEVIATION 14.88 | 53.31 years STANDARD_DEVIATION 11.06 |
| Clinical Global Impression Scale (CGI) | 5.14 units on a scale STANDARD_DEVIATION 0.9 | 5 units on a scale STANDARD_DEVIATION 0.63 | 5.08 units on a scale STANDARD_DEVIATION 0.76 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 5 Participants |
| Hamilton Anxiety Rating Scale (HARS) | 27.14 units on a scale STANDARD_DEVIATION 10.12 | 29.83 units on a scale STANDARD_DEVIATION 7.33 | 28.38 units on a scale STANDARD_DEVIATION 8.69 |
| Hamilton Depression Rating Scale (HDRS) | 25.14 units on a scale STANDARD_DEVIATION 2.97 | 26 units on a scale STANDARD_DEVIATION 2.53 | 25.54 units on a scale STANDARD_DEVIATION 2.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 7 Participants |
| Region of Enrollment United States | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 12 |
| other Total, other adverse events | 2 / 9 | 2 / 12 |
| serious Total, serious adverse events | 0 / 9 | 0 / 12 |
Outcome results
Primary
Mean Change in Hamilton Depression Rating Scale (HDRS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks
The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.
Time frame: 0 weeks-8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline + Riluzole | Mean Change in Hamilton Depression Rating Scale (HDRS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks | -5.67 score on a scale | Standard Deviation 7.09 |
| Sertraline + Placebo | Mean Change in Hamilton Depression Rating Scale (HDRS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks | -13.43 score on a scale | Standard Deviation 6.53 |
p-value: 0.06ANOVA
Primary
Number of Patients Experiencing an Antidepressant Response (>50% Reduction in HDRS) at Endpoint of 8 Weeks
The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.
Time frame: 0 weeks-8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sertraline + Riluzole | Number of Patients Experiencing an Antidepressant Response (>50% Reduction in HDRS) at Endpoint of 8 Weeks | 1 Participants |
| Sertraline + Placebo | Number of Patients Experiencing an Antidepressant Response (>50% Reduction in HDRS) at Endpoint of 8 Weeks | 3 Participants |
p-value: 0.31Chi-squared
Primary
Number of Patients Experiencing Remission From Depression (HDRS<7) at Endpoint of 8 Weeks
The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.
Time frame: 0 weeks-8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sertraline + Riluzole | Number of Patients Experiencing Remission From Depression (HDRS<7) at Endpoint of 8 Weeks | 0 Participants |
| Sertraline + Placebo | Number of Patients Experiencing Remission From Depression (HDRS<7) at Endpoint of 8 Weeks | 1 Participants |
p-value: 0.34Chi-squared
Secondary
Mean Change in Clinical Global Impression (CGI) Scale From Baseline (0 Weeks) to Endpoint at 8 Weeks
The Clinical Global Impression Scale (CGI) is a brief clinician-rated instrument. The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Treatment response ratings should take account of both therapeutic efficacy and treatment-related adverse events and range from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score.
Time frame: 0 weeks-8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline + Riluzole | Mean Change in Clinical Global Impression (CGI) Scale From Baseline (0 Weeks) to Endpoint at 8 Weeks | -0.67 score on a scale | Standard Deviation 0.82 |
| Sertraline + Placebo | Mean Change in Clinical Global Impression (CGI) Scale From Baseline (0 Weeks) to Endpoint at 8 Weeks | -2.71 score on a scale | Standard Deviation 1.98 |
p-value: 0.04ANOVA
Secondary
Mean Change in Hamilton Anxiety Rating Scale (HARS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks
The HARS scale is a clinician rated interview scale designed to measure the signs and symptoms of anxiety. It has 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicate less anxiety.
Time frame: 0 weeks-8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline + Riluzole | Mean Change in Hamilton Anxiety Rating Scale (HARS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks | -9.50 score on a scale | Standard Deviation 10.88 |
| Sertraline + Placebo | Mean Change in Hamilton Anxiety Rating Scale (HARS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks | -15.57 score on a scale | Standard Deviation 7.72 |
p-value: 0.27ANOVA