Efficacy and Tolerability of Riluzole in Treatment Resistant Depression

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01204918
• Collaborator: (none)
• Enrollment: 104
• Locations: 3
• Arms: 3
• Duration (Months): 50
• Patients Per Site: 34.7
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Depression	Drug: Riluzole; Drug: placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 104 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy and Tolerability of Riluzole in Treatment Resistant Depression
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Riluzole addition to SSRI antidepressant Riluzole 100mg added to ongoing SSRI or SNRI antidepressant for 8 weeks	Drug: Riluzole; Riluzole 100mg PO; Other Names: Rilutek
Placebo Comparator: Placebo addition to standard SSRI antidepressant Placebo will be added to ongoing SSRI or SNRI antidepressant treatment for 8 weeks	Drug: placebo; placebo
Experimental: 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	Drug: Riluzole; Riluzole 100mg PO; Other Names: Rilutek ; Drug: placebo; placebo

Outcome Measures

Primary Outcome Measures

1. Change in Montgomery and Asberg Depression Rating Scale (MADRS) [4 weeks of therapy (baseline to week 4)]

   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

2. Change in Montgomery and Asberg Depression Rating Scale (MADRS) [4 weeks of therapy (week 4 to week 8)]

   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

Secondary Outcome Measures

1. Responders Having at Least a 50% Improvement in MADRS Compared to the Baseline [8 weeks therapy]

   Responders having at least a 50% improvement in MADRS compared to the baseline in the sequential parallel design

2. Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) [8 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University, Yale Depression Research Program	New Haven	Connecticut	United States	06511
2	Massachussettes General Hospital, Depression Clinical and Research Center	Boston	Massachusetts	United States	02114
3	Baylor College of Medicine	Houston	Texas	United States	77030

Sponsors and Collaborators

• Yale University

Investigators

• Principal Investigator: 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)

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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. Epub 2006 Dec 4.
• 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.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01204918
• Other Study ID Numbers: 0903004917; 137889; NCT01298427
• First Posted: Sep 17, 2010
• Last Update Posted: Mar 6, 2020
• Last Verified: Mar 1, 2020

• Keywords provided by Yale University: MDD; Depression; Treatment refractory; Glutamate; Riluzole; Major depressive disorder; psychopharmacology; rilutek
• Additional relevant MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Riluzole

Study Results

Participant Flow

Arm/Group Title	Riluzole Addition to SSRI Antidepressant	Riluzole/Placebo Addition to SSRI Antidepressant	Placebo Addition to Standard SSRI Antidepressant
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

Baseline Characteristics

Arm/Group Title	Riluzole Addition to SSRI Antidepressant	Riluzole/Placebo Addition to SSRI Antidepressant	Placebo Addition to Standard SSRI Antidepressant	Total
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 Participants	25	39	40	104
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.3 (12.7)	47.3 (12.1)	46.3 (12.7)	46.3 (12.3)
Sex: Female, Male (Count of Participants)
Female	9 36%	24 61.5%	21 52.5%	54 51.9%
Male	16 64%	15 38.5%	19 47.5%	50 48.1%
Antidepressant (Y/N) (Count of Participants)
Yes	16 64%	25 64.1%	24 60%	65 62.5%
No	9 36%	14 35.9%	16 40%	39 37.5%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

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
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
Measure Participants	25	39	40
Mean (Standard Deviation) [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)
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)

Outcome Measure Data

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
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
Measure Participants	25	39	40
Mean (Standard Deviation) [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
Description	Responders having at least a 50% improvement in MADRS compared to the baseline in the sequential parallel design
Time Frame	8 weeks therapy

Outcome Measure Data

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
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
Measure Participants	25	39	40
Count of Participants [Participants]	6 24%	8 20.5%	10 25%

4. Secondary Outcome

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

Outcome Measure Data

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
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
Measure Participants	25	39	40
Trouble Sleeping	17 68%	24 61.5%	21 52.5%
Nightmares	9 36%	15 38.5%	11 27.5%
Drowsy	14 56%	25 64.1%	22 55%
Nervousness	13 52%	19 48.7%	14 35%
Fatigue	14 56%	26 66.7%	28 70%
Irratibility	15 60%	22 56.4%	23 57.5%
Poor Memory	16 64%	23 59%	24 60%
Poor Concentration	16 64%	28 71.8%	25 62.5%
Strange Feeling/Unreal	4 16%	7 17.9%	5 12.5%
Hearing/Seeing Things	1 4%	2 5.1%	1 2.5%
Abnormal Sensation	3 12%	5 12.8%	3 7.5%
Numbness/Tingling	2 8%	8 20.5%	4 10%
Dizziness	7 28%	10 25.6%	4 10%
Headache	8 32%	14 35.9%	13 32.5%
Blurred Vision	5 20%	8 20.5%	5 12.5%
Ringing Ears	4 16%	9 23.1%	8 20%
Stuffy Nose	5 20%	14 35.9%	10 25%
Dry mouth	3 12%	10 25.6%	10 25%
Drooling/Salivation	2 8%	4 10.3%	0 0%
Muscle Cramp	5 20%	16 41%	12 30%
Muscle Twitch	7 28%	10 25.6%	6 15%
Trouble Sitting	9 36%	16 41%	14 35%
Tremors/Shakiness	8 32%	9 23.1%	6 15%
Poor Coordination	6 24%	11 28.2%	5 12.5%
Slurred Speech	1 4%	5 12.8%	3 7.5%
Rapid Heartbeat	8 32%	13 33.3%	9 22.5%
Hyperventilation	6 24%	7 17.9%	3 7.5%
Chest Pain	4 16%	6 15.4%	2 5%
Nausea/Vomiting	3 12%	5 12.8%	3 7.5%
Stomach Discomfort	5 20%	12 30.8%	9 22.5%
Constipation	3 12%	5 12.8%	10 25%
Diarrhea	2 8%	7 17.9%	11 27.5%
Difficulty Urinating	4 16%	6 15.4%	1 2.5%
Frequent Urination	7 28%	10 25.6%	6 15%
Menstrual Irregularities	0 0%	2 5.1%	1 2.5%
Loss of Sexual Interest	13 52%	26 66.7%	22 55%
Sexual Performance Problems	12 48%	20 51.3%	16 40%
Delayed/Absent Orgasm	9 36%	19 48.7%	16 40%
Sweating Excessively	9 36%	10 25.6%	14 35%
Fluid Retention	4 16%	6 15.4%	8 20%
Decreased Appetite	5 20%	7 17.9%	8 20%
Increased Appetite	8 32%	8 20.5%	15 37.5%
Weight Gain	7 28%	8 20.5%	15 37.5%
Weight Loss	5 20%	7 17.9%	7 17.5%
Skin Rash	3 12%	4 10.3%	3 7.5%
Diminished Mental Acuity	16 64%	22 56.4%	22 55%
Difficulty Finding Words	15 60%	21 53.8%	18 45%
Apathy Emotional Indifference	11 44%	18 46.2%	21 52.5%
Dizzy When Standing Up	8 32%	10 25.6%	2 5%
Bruising	4 16%	2 5.1%	2 5%
Hair Thinning	2 8%	6 15.4%	8 20%
Hot Flashes	2 8%	7 17.9%	12 30%
Clenching Teeth	4 16%	13 33.3%	7 17.5%
Strange Taste in Mouth	3 12%	8 20.5%	5 12.5%
Unable to Sit Still	9 36%	17 43.6%	14 35%

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/39 (0%)		0/40 (0%)
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%)		0/39 (0%)		2/40 (5%)
Nervous system disorders
Global Amnesia	0/25 (0%)	0	0/39 (0%)	0	1/40 (2.5%)	1
Psychiatric disorders
Suicide Attempt	0/25 (0%)	0	0/39 (0%)	0	1/40 (2.5%)	1
Respiratory, thoracic and mediastinal disorders
Bronchitis	1/25 (4%)	1	0/39 (0%)	0	0/40 (0%)	0
Other (Not Including 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	19/25 (76%)		31/39 (79.5%)		34/40 (85%)
Cardiac disorders
Palpitations	0/25 (0%)		1/39 (2.6%)		2/40 (5%)
Eye disorders
Blurred Vision	1/25 (4%)		0/39 (0%)		3/40 (7.5%)
Gastrointestinal disorders
Diarrhea	3/25 (12%)		7/39 (17.9%)		6/40 (15%)
GI Issues	1/25 (4%)		3/39 (7.7%)		5/40 (12.5%)
Nausea	1/25 (4%)		8/39 (20.5%)		11/40 (27.5%)
Stomach Pain	0/25 (0%)		2/39 (5.1%)		1/40 (2.5%)
Vomiting	0/25 (0%)		2/39 (5.1%)		3/40 (7.5%)
General disorders
Abdominal Pain	2/25 (8%)		1/39 (2.6%)		0/40 (0%)
Back Pain	3/25 (12%)		3/39 (7.7%)		4/40 (10%)
Body Aches	0/25 (0%)		0/39 (0%)		2/40 (5%)
Clenching Teeth	0/25 (0%)		2/39 (5.1%)		1/40 (2.5%)
Dizziness	0/25 (0%)		4/39 (10.3%)		3/40 (7.5%)
Fall	0/25 (0%)		0/39 (0%)		2/40 (5%)
Fatigue	5/25 (20%)		6/39 (15.4%)		8/40 (20%)
Headache	7/25 (28%)		11/39 (28.2%)		8/40 (20%)
Insomnia	1/25 (4%)		3/39 (7.7%)		2/40 (5%)
Leg Pain/Stiffness	1/25 (4%)		4/39 (10.3%)		3/40 (7.5%)
Nightmares	1/25 (4%)		2/39 (5.1%)		1/40 (2.5%)
Sexual Dysfunction	1/25 (4%)		2/39 (5.1%)		1/40 (2.5%)
Sleep Disturbance	2/25 (8%)		2/39 (5.1%)		4/40 (10%)
Drowsiness	1/25 (4%)		2/39 (5.1%)		1/40 (2.5%)
Toothache	0/25 (0%)		0/39 (0%)		2/40 (5%)
Vivid Dreams	1/25 (4%)		0/39 (0%)		2/40 (5%)
Infections and infestations
Cold/Flu Symptoms	3/25 (12%)		13/39 (33.3%)		5/40 (12.5%)
Nasal Congestion/Pain	0/25 (0%)		0/39 (0%)		2/40 (5%)
Musculoskeletal and connective tissue disorders
Muscle Pain	1/25 (4%)		1/39 (2.6%)		2/40 (5%)
Nervous system disorders
Numbness	0/25 (0%)		2/39 (5.1%)		1/40 (2.5%)
Sweating	0/25 (0%)		0/39 (0%)		2/40 (5%)
Tingling Sensation	1/25 (4%)		2/39 (5.1%)		1/40 (2.5%)
Psychiatric disorders
Anxiety	0/25 (0%)		0/39 (0%)		2/40 (5%)
Renal and urinary disorders
Frequent Urination	2/25 (8%)		2/39 (5.1%)		0/40 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/25 (0%)		3/39 (7.7%)		1/40 (2.5%)
Skin and subcutaneous tissue disorders
Bruising	1/25 (4%)		0/39 (0%)		2/40 (5%)
Rash	1/25 (4%)		3/39 (7.7%)		0/40 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.