Efficacy and Tolerability of Riluzole in Treatment Resistant Depression

NCT01204918 | Completed Phase 2 Results DMC

• 2 other identifiers: 0903004917137889
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 3

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).

Conditions

Depression

Keywords

MDD; Depression; Treatment refractory; Glutamate; Riluzole; Major depressive disorder; psychopharmacology; rilutek

Outcome Measures

Primary Outcomes (2)

• Change in Montgomery and Asberg Depression Rating Scale (MADRS)

  This 10 item instrument is completed by the clinician by using a structured interview and defined anchor points, and aims to quantify the degree of depression over the past 7 days. The MADRS is a widely studied instrument for depression, and its reliability and validity are high. This instrument is administered at every study visit during the double-blind RCT, and at the screening, and baseline. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Usual cutoff points are: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression \>34 - severe depression

  4 weeks of therapy (baseline to week 4)

• Change in Montgomery and Asberg Depression Rating Scale (MADRS)

  This 10 item instrument is completed by the clinician by using a structured interview and defined anchor points, and aims to quantify the degree of depression over the past 7 days. The MADRS is a widely studied instrument for depression, and its reliability and validity are high. This instrument is administered at every study visit during the double-blind RCT, and at the screening, and baseline. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Usual cutoff points are: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression \>34 - severe depression

  4 weeks of therapy (week 4 to week 8)

Secondary Outcomes (2)

• Responders Having at Least a 50% Improvement in MADRS Compared to the Baseline

  8 weeks therapy

• Systematic Assessment for Treatment Emergent Events (SAFTEE-SI)

  8 weeks

Study Arms (3)

Riluzole addition to SSRI antidepressant

EXPERIMENTAL

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

Drug: Riluzole

Placebo addition to standard SSRI antidepressant

PLACEBO COMPARATOR

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

Drug: placebo

Riluzole/Placebo addition to SSRI antidepressant

EXPERIMENTAL

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

Drug: Riluzole; Drug: placebo

Interventions

Riluzole DRUG

Riluzole 100mg PO

Also known as: Rilutek

Riluzole addition to SSRI antidepressant; Riluzole/Placebo addition to SSRI antidepressant

placebo DRUG

placebo

Placebo addition to standard SSRI antidepressant; Riluzole/Placebo addition to SSRI antidepressant

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65
• Written informed consent
• Meets DSM-IV criteria (by Structured Clinical Interview for DSM-IV - SCID-I/P) for MDD, current
• Inventory of Depressive Symptomatology - Self-Rated (IDS-SR30) score of \> 20 at screening, baseline and start of double-blind phase (Phase 2)
• Montgomery Asberg Depression Rating Scale (MADRS) score of 18 or higher at baseline and start of Phase 2.

You may not qualify if:

• 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)
• Patients who no longer meet DSM-IV criteria for MDD during the baseline visit
• Patients who demonstrate \> 50% decrease in depressive symptoms as reflected by the IDS-SR total score from screen to baseline
• 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.
• Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease
• 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)
• History of a seizure disorder or clinical evidence of untreated hypothyroidism
• Patients requiring excluded medications (see Table 3 for details)
• Psychotic features in the current episode or a history of psychotic features, as assessed by SCID
• Any investigational psychotropic drug within the last 3 months
• Have failed 3 or more adequate antidepressant trials during the current Major Depressive Episode by MGH-ATRQ criteria.
• Patients with a history of antidepressant-induced hypomania.
• 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.
• Axis II personality disorders that are the primary purpose of treatment, or would interfere with a patient's safety or compliance.
• Patients currently being treated for a respiratory disorder (including asthma or COPD)

Sponsors & Collaborators

• Yale University: lead

Study Sites (3)

Yale University, Yale Depression Research Program

New Haven, Connecticut, 06511, United States

Location

Massachussettes General Hospital, Depression Clinical and Research Center

Boston, Massachusetts, 02114, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (5)

• 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.

  PMID: 17141740 BACKGROUND

• 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.

  PMID: 14702270 BACKGROUND

• 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.

  PMID: 40398609 DERIVED

• 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.

  PMID: 39955416 DERIVED

• 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.

  PMID: 35092868 DERIVED

MeSH Terms

Conditions

Depression; Depressive Disorder, Major

Interventions

Riluzole

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Gerard Sanacora, PhD, MD: Professor of Psychiatry; Director, Yale Depression Research Program
• Organization: Yale University

gerard.sanacora@yale.edu

(203) 974-7535

Study Officials

• Gerard Sanacora, MD PhD

  Yale University

  PRINCIPAL INVESTIGATOR

• Maurizio Fava, MD

  Massachusettes General Hospital

  PRINCIPAL INVESTIGATOR

• Sanjay Matthew, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Carlos Zarate, MD

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2010
• First Posted: September 17, 2010
• Study Start: June 1, 2011
• Primary Completion: May 1, 2015
• Study Completion: August 1, 2015
• Last Updated: March 6, 2020
• Results First Posted: February 8, 2018

Record last verified: 2020-03

Locations

US (3)