Efficacy and Tolerability of Riluzole in Treatment Resistant Depression

Yale University

Status and phase: Completed; Phase 2

Conditions: Depression

Treatments: Drug: Riluzole; Drug: placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01204918

137889 (Other Identifier)

0903004917

Details and patient eligibility

About

This study aims to examine the antidepressant efficacy of riluzole, employing a randomized, double-blind, placebo-controlled, adjunctive trial in treatment-resistant major depressive disorder (TRD).

Full description

This study aims to examine the antidepressant efficacy of riluzole, employing a randomized, double-blind, placebo-controlled, 8 week trial of adjunctive trial in treatment-resistant major depressive disorder (TRD). Preclinical studies have shown riluzole to modulate Glu release and clearance, and to have potent neuroprotective properties, promoting neuro-resiliency. Other preclinical data now also show the drug to have antidepressant-like effects in rodent models used to screen for antidepressant activity. In addition, several small open-label clinical studies further suggest riluzole has antidepressant and anxiolytic properties, even in patients who do not respond to standard monoaminergic antidepressant and anxiolytic medications.

Enrollment: 104 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Group A inclusion/exclusion

Inclusion Criteria:

1. Age 18-65
2. Written informed consent
3. Meets DSM-IV criteria (by Structured Clinical Interview for DSM-IV - SCID-I/P) for MDD, current
4. Inventory of Depressive Symptomatology - Self-Rated (IDS-SR30) score of > 20 at screening, baseline and start of double-blind phase (Phase 2)
5. May have a history of failure to respond to up to two FDA-approved antidepressants at adequate doses during the current episode for at least 8 weeks, and for inclusion into the Phase 2 subjects must have failed the 8-week prospective citalopram treatment.
6. Montgomery Asberg Depression Rating Scale (MADRS) score of 18 or higher at baseline and start of Phase 2.

Exclusion Criteria:

1. Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy)
2. Patients who no longer meet DSM-IV criteria for MDD during the baseline visit
3. Patients who demonstrate > 50% decrease in depressive symptoms as reflected by the IDS-SR total score from screen to baseline
4. Serious suicide or homicide risk, as assessed by evaluating clinician A serious suicide risk will be considered an inability to control suicide attempts, imminent risk of suicide in the investigator's judgment, or a history of serious suicidal behavior, which is defined using the Columbia-Suicide Severity Rating Scale (C-SSRS) as either (1) one or more actual suicide attempts in the 3 years before study entry with the lethality rated at 3 or higher, or (2) one or more interrupted suicide attempts with a potential lethality judged to result in serious injury or death.
5. Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease
6. The following DSM-IV diagnoses: substance use disorders active within the last six months, any bipolar disorder (current or past), any psychotic disorder (current or past)
7. History of a seizure disorder or clinical evidence of untreated hypothyroidism
8. Patients requiring excluded medications (see Table 3 for details)
9. Psychotic features in the current episode or a history of psychotic features, as assessed by SCID
10. Any investigational psychotropic drug within the last 3 months
11. Have failed 3 or more adequate antidepressant trials during the current Major Depressive Episode by MGH-ATRQ criteria.
12. Patients with a history of antidepressant-induced hypomania.
13. Patients with any evidence of clinically significant liver abnormalities, or any liver transaminase level >1.5 X ULN at initial screening, or >5 x ULN during Phase 2 treatment.
14. Axis II personality disorders that are the primary purpose of treatment, or would interfere with a patient's safety or compliance.
15. Patients currently being treated for a respiratory disorder (including asthma or COPD)
16. Any subject who scores a 5 or higher on item #10 of the MADRS

Group B inclusion/exclusion

Inclusion criteria:

1. Age 18-65
2. Written informed consent
3. Meets DSM-IV criteria (by Structured Clinical Interview for DSM-IV - SCID-I/P) for MDD, current
4. Inventory of Depressive Symptomatology - Self-Rated (IDS-SR30) score of > 20 at screening and baseline visits, that is at the start of Phase 2
5. Has a history of failure to respond to 1, 2, or 3 FDA-approved antidepressants at adequate doses during the current episode for at least 8 weeks, as defined by the MGH Antidepressant Treatment Response Questionnaire (MGH-ATRQ), and must be currently on the failed SSRI for at least 8 weeks and on a stable dose for at least 4 weeks.
6. Montgomery Asberg Depression Rating Scale (MADRS) score of 18 or higher at baseline and start of Phase 2.

Exclusion Criteria

1. Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy)
2. Patients who no longer meet DSM-IV criteria for MDD during the baseline visit
3. Serious suicide or homicide risk, as assessed by evaluating clinician A serious suicide risk will be considered an inability to control suicide attempts, imminent risk of suicide in the investigator's judgment, or a history of serious suicidal behavior, which is defined using the Columbia-Suicide Severity Rating Scale (C-SSRS) as either (1) one or more actual suicide attempts in the 3 years before study entry with the lethality rated at 3 or higher, or (2) one or more interrupted suicide attempts with a potential lethality judged to result in serious injury or death.
4. Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease
5. The following DSM-IV diagnoses: substance use disorders active within the last six months, any bipolar disorder (current or past), any psychotic disorder (current or past)
6. History of a seizure disorder or clinical evidence of untreated hypothyroidism;
7. Patients requiring excluded medications (see Table 3 for details)
8. Psychotic features in the current episode or a history of psychotic features, as assessed by SCID
9. Any investigational psychotropic drug within the last 3 months
10. Have failed 3 or more adequate antidepressant trials during the current Major Depressive Episode by MGH-ATRQ criteria.
11. Patients with a history of antidepressant-induced hypomania.
12. Patients with any evidence of clinically significant liver abnormalities, or any liver transaminase level >2 X ULN at initial screening, or >5 x ULN during Phase 2 treatment.
13. Axis II personality disorders that are the primary purpose of treatment, or would interfere with a patients safety or compliance.
14. Patients currently being treated for a respiratory disorder (including asthma or COPD)
15. Any subject who scores a 5 or higher on item #10 of the MADRS

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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104 participants in 3 patient groups, including a placebo group

Riluzole addition to SSRI antidepressant

Experimental group

Description:

Riluzole 100mg added to ongoing SSRI or SNRI antidepressant for 8 weeks

Treatment:

Drug: Riluzole

Placebo addition to standard SSRI antidepressant

Placebo Comparator group

Description:

Placebo will be added to ongoing SSRI or SNRI antidepressant treatment for 8 weeks

Treatment:

Drug: placebo

Riluzole/Placebo addition to SSRI antidepressant

Experimental group

Description:

Riluzole 100mg added to ongoing SSRI or SNRI antidepressant for 4 weeks and placebo will added to ongoing SSRI or SNRI antidepressant treatment for 4 weeks

Treatment:

Drug: placebo

Drug: Riluzole