Efficacy and Tolerability of Riluzole in Treatment Resistant Depression

NCT ID: NCT01204918

Last Updated: 2020-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2015-08-31

Brief Summary

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).

Detailed 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.

Conditions

Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Riluzole addition to SSRI antidepressant

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

Group Type: EXPERIMENTAL

Riluzole

Intervention Type: DRUG

Riluzole 100mg PO

Placebo addition to standard SSRI antidepressant

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo

Riluzole/Placebo addition to SSRI antidepressant

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

Group Type: EXPERIMENTAL

Riluzole

Intervention Type: DRUG

Riluzole 100mg PO

placebo

Intervention Type: DRUG

placebo

Interventions

Riluzole

Riluzole 100mg PO

Intervention Type: DRUG

placebo

placebo

Intervention Type: DRUG

Other Intervention Names

Rilutek

Eligibility Criteria

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.

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. 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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gerard Sanacora, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Maurizio Fava, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusettes General Hospital

Sanjay Matthew, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Carlos Zarate, MD

Role: PRINCIPAL_INVESTIGATOR

National Institute of Mental Health (NIMH)

Locations

Yale University, Yale Depression Research Program

New Haven, Connecticut, United States

Massachussettes General Hospital, Depression Clinical and Research Center

Boston, Massachusetts, United States

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

References

Sanacora G, Kendell SF, Levin Y, Simen AA, Fenton LR, Coric V, Krystal JH. Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms. Biol Psychiatry. 2007 Mar 15;61(6):822-5. doi: 10.1016/j.biopsych.2006.08.037. Epub 2006 Dec 4.

Reference Type: BACKGROUND

PMID: 17141740 (View on PubMed)

Zarate CA Jr, Payne JL, Quiroz J, Sporn J, Denicoff KK, Luckenbaugh D, Charney DS, Manji HK. An open-label trial of riluzole in patients with treatment-resistant major depression. Am J Psychiatry. 2004 Jan;161(1):171-4. doi: 10.1176/appi.ajp.161.1.171.

Reference Type: BACKGROUND

PMID: 14702270 (View on PubMed)

Kheirkhah M, Hejazi NS, Nugent AC, Gilbert JR, Leistritz L, Walter M, Duncan WC Jr, Goldman D, Zarate CA Jr. Exploring the link between waking gamma and sleep delta power in healthy volunteers and individuals with treatment-resistant depression. J Affect Disord. 2025 Sep 15;385:119448. doi: 10.1016/j.jad.2025.119448. Epub 2025 May 19.

Reference Type: DERIVED

PMID: 40398609 (View on PubMed)

Kheirkhah M, Duncan WC Jr, Yuan Q, Wang PR, Jamalabadi H, Leistritz L, Walter M, Goldman D, Zarate CA Jr, Hejazi NS. REM density predicts rapid antidepressant response to ketamine in individuals with treatment-resistant depression. Neuropsychopharmacology. 2025 May;50(6):941-946. doi: 10.1038/s41386-025-02066-7. Epub 2025 Feb 15.

Reference Type: DERIVED

PMID: 39955416 (View on PubMed)

Hejazi NS, Farmer CA, Oppenheimer M, Falodun TB, Park LT, Duncan WC Jr, Zarate CA Jr. The relationship between the HDRS insomnia items and polysomnographic (PSG) measures in individuals with treatment-resistant depression. J Psychiatr Res. 2022 Apr;148:27-33. doi: 10.1016/j.jpsychires.2022.01.022. Epub 2022 Jan 11.

Reference Type: DERIVED

PMID: 35092868 (View on PubMed)

Other Identifiers

137889

Identifier Type: OTHER

Identifier Source: secondary_id

0903004917

Identifier Type: -

Identifier Source: org_study_id

NCT01298427

Identifier Type: -

Identifier Source: nct_alias