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Efficacy and Tolerability of Riluzole in Treatment Resistant Depression

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ClinicalTrials.gov Identifier: NCT01204918
Recruitment Status : Completed
First Posted : September 17, 2010
Results First Posted : February 8, 2018
Last Update Posted : February 8, 2018
Sponsor:
Information provided by (Responsible Party):
Yale University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Depression
Interventions Drug: Riluzole
Drug: placebo
Enrollment 104
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Riluzole Addition to SSRI Antidepressant Riluzole/Placebo Addition to SSRI Antidepressant Placebo Addition to Standard SSRI Antidepressant
Hide Arm/Group Description

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

Riluzole: Riluzole 100mg PO

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

Riluzole: Riluzole 100mg PO

placebo: placebo

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

placebo: placebo

Period Title: Overall Study
Started 25 39 40
Stage 1 Begin 25 39 40
Stage 1 End 22 35 36
Stage 2 Begin 22 35 36
Stage 2 End 21 29 35
Completed 21 29 35
Not Completed 4 10 5
Reason Not Completed
Withdrawal by Subject             4             10             5
Arm/Group Title Riluzole Addition to SSRI Antidepressant Riluzole/Placebo Addition to SSRI Antidepressant Placebo Addition to Standard SSRI Antidepressant Total
Hide Arm/Group Description

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

Riluzole: Riluzole 100mg PO

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

Riluzole: Riluzole 100mg PO

placebo: placebo

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

placebo: placebo

Total of all reporting groups
Overall Number of Baseline Participants 25 39 40 104
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants 39 participants 40 participants 104 participants
46.3  (12.7) 47.3  (12.1) 46.3  (12.7) 46.3  (12.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 39 participants 40 participants 104 participants
Female
9
  36.0%
24
  61.5%
21
  52.5%
54
  51.9%
Male
16
  64.0%
15
  38.5%
19
  47.5%
50
  48.1%
Antidepressant (Y/N)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 39 participants 40 participants 104 participants
Yes
16
  64.0%
25
  64.1%
24
  60.0%
65
  62.5%
No
9
  36.0%
14
  35.9%
16
  40.0%
39
  37.5%
1.Primary Outcome
Title Change in Montgomery and Asberg Depression Rating Scale (MADRS)
Hide Description

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

Time Frame 4 weeks of therapy (baseline to week 4)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Riluzole Addition to SSRI Antidepressant Riluzole/Placebo Addition to SSRI Antidepressant Placebo Addition to Standard SSRI Antidepressant
Hide Arm/Group Description:

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

Riluzole: Riluzole 100mg PO

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

Riluzole: Riluzole 100mg PO

placebo: placebo

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

placebo: placebo

Overall Number of Participants Analyzed 25 39 40
Mean (Standard Deviation)
Unit of Measure: units on a scale
3.20  (3.86) 5.77  (0.52) 4.83  (7.85)
2.Primary Outcome
Title Change in Montgomery and Asberg Depression Rating Scale (MADRS)
Hide Description

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

Time Frame 4 weeks of therapy (week 4 to week 8)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Riluzole Addition to SSRI Antidepressant Riluzole/Placebo Addition to SSRI Antidepressant Placebo Addition to Standard SSRI Antidepressant
Hide Arm/Group Description:

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

Riluzole: Riluzole 100mg PO

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

Riluzole: Riluzole 100mg PO

placebo: placebo

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

placebo: placebo

Overall Number of Participants Analyzed 25 39 40
Mean (Standard Deviation)
Unit of Measure: units on a scale
4.13  (6.82) 0.84  (5.79) 3.87  (6.49)
3.Secondary Outcome
Title Responders Having at Least a 50% Improvement in MADRS Compared to the Baseline
Hide Description Responders having at least a 50% improvement in MADRS compared to the baseline in the sequential parallel design
Time Frame 8 weeks therapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Riluzole Addition to SSRI Antidepressant Riluzole/Placebo Addition to SSRI Antidepressant Placebo Addition to Standard SSRI Antidepressant
Hide Arm/Group Description:

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

Riluzole: Riluzole 100mg PO

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

Riluzole: Riluzole 100mg PO

placebo: placebo

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

placebo: placebo

Overall Number of Participants Analyzed 25 39 40
Measure Type: Count of Participants
Unit of Measure: Participants
6
  24.0%
8
  20.5%
10
  25.0%
4.Secondary Outcome
Title Systematic Assessment for Treatment Emergent Events (SAFTEE-SI)
Hide Description A commonly used instrument originally developed by NIMH and adapted into a self-report instrument. The version of the scale that we plan to use examines in a systematic fashion all possible treatment-emergent side effects and probes specific adverse symptoms, including suicidal thoughts and behaviors, and self-injurious behavior. Presented below are counts of people that had experienced the event by 8 weeks.
Time Frame 8 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects are included in the analysis- with the exception of sex specific conditions.
Arm/Group Title Riluzole Addition to SSRI Antidepressant Riluzole/Placebo Addition to SSRI Antidepressant Placebo Addition to Standard SSRI Antidepressant
Hide Arm/Group Description:

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

Riluzole: Riluzole 100mg PO

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

Riluzole: Riluzole 100mg PO

placebo: placebo

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

placebo: placebo

Overall Number of Participants Analyzed 25 39 40
Measure Type: Number
Unit of Measure: participants
Trouble Sleeping Number Analyzed 25 participants 39 participants 40 participants
17 24 21
Nightmares Number Analyzed 25 participants 39 participants 40 participants
9 15 11
Drowsy Number Analyzed 25 participants 39 participants 40 participants
14 25 22
Nervousness Number Analyzed 25 participants 39 participants 40 participants
13 19 14
Fatigue Number Analyzed 25 participants 39 participants 40 participants
14 26 28
Irratibility Number Analyzed 25 participants 39 participants 40 participants
15 22 23
Poor Memory Number Analyzed 25 participants 39 participants 40 participants
16 23 24
Poor Concentration Number Analyzed 25 participants 39 participants 40 participants
16 28 25
Strange Feeling/Unreal Number Analyzed 25 participants 39 participants 40 participants
4 7 5
Hearing/Seeing Things Number Analyzed 25 participants 39 participants 40 participants
1 2 1
Abnormal Sensation Number Analyzed 25 participants 39 participants 40 participants
3 5 3
Numbness/Tingling Number Analyzed 25 participants 39 participants 40 participants
2 8 4
Dizziness Number Analyzed 25 participants 39 participants 40 participants
7 10 4
Headache Number Analyzed 25 participants 39 participants 40 participants
8 14 13
Blurred Vision Number Analyzed 25 participants 39 participants 40 participants
5 8 5
Ringing Ears Number Analyzed 25 participants 39 participants 40 participants
4 9 8
Stuffy Nose Number Analyzed 25 participants 39 participants 40 participants
5 14 10
Dry mouth Number Analyzed 25 participants 39 participants 40 participants
3 10 10
Drooling/Salivation Number Analyzed 25 participants 39 participants 40 participants
2 4 0
Muscle Cramp Number Analyzed 25 participants 39 participants 40 participants
5 16 12
Muscle Twitch Number Analyzed 25 participants 39 participants 40 participants
7 10 6
Trouble Sitting Number Analyzed 25 participants 39 participants 40 participants
9 16 14
Tremors/Shakiness Number Analyzed 25 participants 39 participants 40 participants
8 9 6
Poor Coordination Number Analyzed 25 participants 39 participants 40 participants
6 11 5
Slurred Speech Number Analyzed 25 participants 39 participants 40 participants
1 5 3
Rapid Heartbeat Number Analyzed 25 participants 39 participants 40 participants
8 13 9
Hyperventilation Number Analyzed 25 participants 39 participants 40 participants
6 7 3
Chest Pain Number Analyzed 25 participants 39 participants 40 participants
4 6 2
Nausea/Vomiting Number Analyzed 25 participants 39 participants 40 participants
3 5 3
Stomach Discomfort Number Analyzed 25 participants 39 participants 40 participants
5 12 9
Constipation Number Analyzed 25 participants 39 participants 40 participants
3 5 10
Diarrhea Number Analyzed 25 participants 39 participants 40 participants
2 7 11
Difficulty Urinating Number Analyzed 25 participants 39 participants 40 participants
4 6 1
Frequent Urination Number Analyzed 25 participants 39 participants 40 participants
7 10 6
Menstrual Irregularities Number Analyzed 9 participants 24 participants 21 participants
0 2 1
Loss of Sexual Interest Number Analyzed 25 participants 39 participants 40 participants
13 26 22
Sexual Performance Problems Number Analyzed 25 participants 39 participants 40 participants
12 20 16
Delayed/Absent Orgasm Number Analyzed 25 participants 39 participants 40 participants
9 19 16
Sweating Excessively Number Analyzed 25 participants 39 participants 40 participants
9 10 14
Fluid Retention Number Analyzed 25 participants 39 participants 40 participants
4 6 8
Decreased Appetite Number Analyzed 25 participants 39 participants 40 participants
5 7 8
Increased Appetite Number Analyzed 25 participants 39 participants 40 participants
8 8 15
Weight Gain Number Analyzed 25 participants 39 participants 40 participants
7 8 15
Weight Loss Number Analyzed 25 participants 39 participants 40 participants
5 7 7
Skin Rash Number Analyzed 25 participants 39 participants 40 participants
3 4 3
Diminished Mental Acuity Number Analyzed 25 participants 39 participants 40 participants
16 22 22
Difficulty Finding Words Number Analyzed 25 participants 39 participants 40 participants
15 21 18
Apathy Emotional Indifference Number Analyzed 25 participants 39 participants 40 participants
11 18 21
Dizzy When Standing Up Number Analyzed 25 participants 39 participants 40 participants
8 10 2
Bruising Number Analyzed 25 participants 39 participants 40 participants
4 2 2
Hair Thinning Number Analyzed 25 participants 39 participants 40 participants
2 6 8
Hot Flashes Number Analyzed 25 participants 39 participants 40 participants
2 7 12
Clenching Teeth Number Analyzed 25 participants 39 participants 40 participants
4 13 7
Strange Taste in Mouth Number Analyzed 25 participants 39 participants 40 participants
3 8 5
Unable to Sit Still Number Analyzed 25 participants 39 participants 40 participants
9 17 14
Time Frame 8 weeks
Adverse Event Reporting Description These are events that were deemed to not be present at or before baseline and were verified by the study team. These data are not to be confused with the SAFTEE secondary outcome reporting, which was self reported and not verified nor attributed to the study. The SAE's reported in this table occurred after discontinuing the study medication.
 
Arm/Group Title Riluzole Addition to SSRI Antidepressant Riluzole/Placebo Addition to SSRI Antidepressant Placebo Addition to Standard SSRI Antidepressant
Hide Arm/Group Description

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

Riluzole: Riluzole 100mg PO

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

Riluzole: Riluzole 100mg PO

placebo: placebo

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

placebo: placebo

All-Cause Mortality
Riluzole Addition to SSRI Antidepressant Riluzole/Placebo Addition to SSRI Antidepressant Placebo Addition to Standard SSRI Antidepressant
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/25 (0.00%)      0/39 (0.00%)      0/40 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Riluzole Addition to SSRI Antidepressant Riluzole/Placebo Addition to SSRI Antidepressant Placebo Addition to Standard SSRI Antidepressant
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/25 (4.00%)      0/39 (0.00%)      2/40 (5.00%)    
Nervous system disorders       
Global Amnesia *  0/25 (0.00%)  0 0/39 (0.00%)  0 1/40 (2.50%)  1
Psychiatric disorders       
Suicide Attempt *  0/25 (0.00%)  0 0/39 (0.00%)  0 1/40 (2.50%)  1
Respiratory, thoracic and mediastinal disorders       
Bronchitis *  1/25 (4.00%)  1 0/39 (0.00%)  0 0/40 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Riluzole Addition to SSRI Antidepressant Riluzole/Placebo Addition to SSRI Antidepressant Placebo Addition to Standard SSRI Antidepressant
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/25 (76.00%)      31/39 (79.49%)      34/40 (85.00%)    
Cardiac disorders       
Palpitations   0/25 (0.00%)  1/39 (2.56%)  2/40 (5.00%) 
Eye disorders       
Blurred Vision   1/25 (4.00%)  0/39 (0.00%)  3/40 (7.50%) 
Gastrointestinal disorders       
Diarrhea   3/25 (12.00%)  7/39 (17.95%)  6/40 (15.00%) 
GI Issues   1/25 (4.00%)  3/39 (7.69%)  5/40 (12.50%) 
Nausea   1/25 (4.00%)  8/39 (20.51%)  11/40 (27.50%) 
Stomach Pain   0/25 (0.00%)  2/39 (5.13%)  1/40 (2.50%) 
Vomiting   0/25 (0.00%)  2/39 (5.13%)  3/40 (7.50%) 
General disorders       
Abdominal Pain   2/25 (8.00%)  1/39 (2.56%)  0/40 (0.00%) 
Back Pain   3/25 (12.00%)  3/39 (7.69%)  4/40 (10.00%) 
Body Aches   0/25 (0.00%)  0/39 (0.00%)  2/40 (5.00%) 
Clenching Teeth   0/25 (0.00%)  2/39 (5.13%)  1/40 (2.50%) 
Dizziness   0/25 (0.00%)  4/39 (10.26%)  3/40 (7.50%) 
Fall   0/25 (0.00%)  0/39 (0.00%)  2/40 (5.00%) 
Fatigue   5/25 (20.00%)  6/39 (15.38%)  8/40 (20.00%) 
Headache   7/25 (28.00%)  11/39 (28.21%)  8/40 (20.00%) 
Insomnia   1/25 (4.00%)  3/39 (7.69%)  2/40 (5.00%) 
Leg Pain/Stiffness   1/25 (4.00%)  4/39 (10.26%)  3/40 (7.50%) 
Nightmares   1/25 (4.00%)  2/39 (5.13%)  1/40 (2.50%) 
Sexual Dysfunction   1/25 (4.00%)  2/39 (5.13%)  1/40 (2.50%) 
Sleep Disturbance   2/25 (8.00%)  2/39 (5.13%)  4/40 (10.00%) 
Drowsiness   1/25 (4.00%)  2/39 (5.13%)  1/40 (2.50%) 
Toothache   0/25 (0.00%)  0/39 (0.00%)  2/40 (5.00%) 
Vivid Dreams   1/25 (4.00%)  0/39 (0.00%)  2/40 (5.00%) 
Infections and infestations       
Cold/Flu Symptoms   3/25 (12.00%)  13/39 (33.33%)  5/40 (12.50%) 
Nasal Congestion/Pain   0/25 (0.00%)  0/39 (0.00%)  2/40 (5.00%) 
Musculoskeletal and connective tissue disorders       
Muscle Pain   1/25 (4.00%)  1/39 (2.56%)  2/40 (5.00%) 
Nervous system disorders       
Numbness   0/25 (0.00%)  2/39 (5.13%)  1/40 (2.50%) 
Sweating   0/25 (0.00%)  0/39 (0.00%)  2/40 (5.00%) 
Tingling Sensation   1/25 (4.00%)  2/39 (5.13%)  1/40 (2.50%) 
Psychiatric disorders       
Anxiety   0/25 (0.00%)  0/39 (0.00%)  2/40 (5.00%) 
Renal and urinary disorders       
Frequent Urination   2/25 (8.00%)  2/39 (5.13%)  0/40 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough   0/25 (0.00%)  3/39 (7.69%)  1/40 (2.50%) 
Skin and subcutaneous tissue disorders       
Bruising   1/25 (4.00%)  0/39 (0.00%)  2/40 (5.00%) 
Rash   1/25 (4.00%)  3/39 (7.69%)  0/40 (0.00%) 
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Gerard Sanacora, PhD, MD: Professor of Psychiatry; Director, Yale Depression Research Program
Organization: Yale University
Phone: (203) 974-7535
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01204918     History of Changes
Obsolete Identifiers: NCT01298427
Other Study ID Numbers: HIC#0903004917
First Submitted: September 16, 2010
First Posted: September 17, 2010
Results First Submitted: October 10, 2017
Results First Posted: February 8, 2018
Last Update Posted: February 8, 2018