Depression
Conditions
Keywords
MDD, Depression, Treatment refractory, Glutamate, Riluzole, Major depressive disorder, psychopharmacology, rilutek
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.
Interventions
DRUGRiluzole
Riluzole 100mg PO
DRUGplacebo
placebo
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Riluzole Addition to SSRI Antidepressant Riluzole 100mg added to ongoing SSRI or SNRI antidepressant for 8 weeks
Riluzole: Riluzole 100mg PO | 25 |
| 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
Riluzole: Riluzole 100mg PO
placebo: placebo | 39 |
| Placebo Addition to Standard SSRI Antidepressant Placebo will be added to ongoing SSRI or SNRI antidepressant treatment for 8 weeks
placebo: placebo | 40 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 4 | 10 | 5 |
Baseline characteristics
| Characteristic | Riluzole Addition to SSRI Antidepressant | Riluzole/Placebo Addition to SSRI Antidepressant | Placebo Addition to Standard SSRI Antidepressant | Total |
|---|---|---|---|---|
| Age, Continuous | 46.3 years STANDARD_DEVIATION 12.7 | 47.3 years STANDARD_DEVIATION 12.1 | 46.3 years STANDARD_DEVIATION 12.7 | 46.3 years STANDARD_DEVIATION 12.3 |
| Antidepressant (Y/N) No | 9 Participants | 14 Participants | 16 Participants | 39 Participants |
| Antidepressant (Y/N) Yes | 16 Participants | 25 Participants | 24 Participants | 65 Participants |
| Sex: Female, Male Female | 9 Participants | 24 Participants | 21 Participants | 54 Participants |
| Sex: Female, Male Male | 16 Participants | 15 Participants | 19 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 39 | 0 / 40 |
| other Total, other adverse events | 19 / 25 | 31 / 39 | 34 / 40 |
| serious Total, serious adverse events | 1 / 25 | 0 / 39 | 2 / 40 |
Outcome results
Primary
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
Time frame: 4 weeks of therapy (baseline to week 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riluzole Addition to SSRI Antidepressant | Change in Montgomery and Asberg Depression Rating Scale (MADRS) | 3.20 units on a scale | Standard Deviation 3.86 |
| Riluzole/Placebo Addition to SSRI Antidepressant | Change in Montgomery and Asberg Depression Rating Scale (MADRS) | 5.77 units on a scale | Standard Deviation 0.52 |
| Placebo Addition to Standard SSRI Antidepressant | Change in Montgomery and Asberg Depression Rating Scale (MADRS) | 4.83 units on a scale | Standard Deviation 7.85 |
Primary
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
Time frame: 4 weeks of therapy (week 4 to week 8)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riluzole Addition to SSRI Antidepressant | Change in Montgomery and Asberg Depression Rating Scale (MADRS) | 4.13 units on a scale | Standard Deviation 6.82 |
| Riluzole/Placebo Addition to SSRI Antidepressant | Change in Montgomery and Asberg Depression Rating Scale (MADRS) | 0.84 units on a scale | Standard Deviation 5.79 |
| Placebo Addition to Standard SSRI Antidepressant | Change in Montgomery and Asberg Depression Rating Scale (MADRS) | 3.87 units on a scale | Standard Deviation 6.49 |
Secondary
Responders Having at Least a 50% Improvement in MADRS Compared to the Baseline
Responders having at least a 50% improvement in MADRS compared to the baseline in the sequential parallel design
Time frame: 8 weeks therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Riluzole Addition to SSRI Antidepressant | Responders Having at Least a 50% Improvement in MADRS Compared to the Baseline | 6 Participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Responders Having at Least a 50% Improvement in MADRS Compared to the Baseline | 8 Participants |
| Placebo Addition to Standard SSRI Antidepressant | Responders Having at Least a 50% Improvement in MADRS Compared to the Baseline | 10 Participants |
Secondary
Systematic Assessment for Treatment Emergent Events (SAFTEE-SI)
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
Population: All subjects are included in the analysis- with the exception of sex specific conditions.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Irratibility | 15 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Delayed/Absent Orgasm | 9 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Muscle Cramp | 5 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Nightmares | 9 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Sexual Performance Problems | 12 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Muscle Twitch | 7 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Dizzy When Standing Up | 8 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Loss of Sexual Interest | 13 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Trouble Sitting | 9 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Poor Memory | 16 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Menstrual Irregularities | 0 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Tremors/Shakiness | 8 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Abnormal Sensation | 3 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Frequent Urination | 7 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Poor Coordination | 6 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Apathy Emotional Indifference | 11 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Difficulty Urinating | 4 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Slurred Speech | 1 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Poor Concentration | 16 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Diarrhea | 2 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Rapid Heartbeat | 8 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Clenching Teeth | 4 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Constipation | 3 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Hyperventilation | 6 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Difficulty Finding Words | 15 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Stomach Discomfort | 5 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Chest Pain | 4 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Strange Feeling/Unreal | 4 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Nausea/Vomiting | 3 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Drowsy | 14 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Diminished Mental Acuity | 16 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Trouble Sleeping | 17 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Skin Rash | 3 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Numbness/Tingling | 2 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Hot Flashes | 2 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Weight Loss | 5 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Dizziness | 7 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Nervousness | 13 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Weight Gain | 7 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Headache | 8 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Unable to Sit Still | 9 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Hearing/Seeing Things | 1 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Blurred Vision | 5 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Hair Thinning | 2 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Increased Appetite | 8 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Ringing Ears | 4 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Fatigue | 14 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Decreased Appetite | 5 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Stuffy Nose | 5 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Strange Taste in Mouth | 3 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Fluid Retention | 4 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Dry mouth | 3 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Bruising | 4 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Sweating Excessively | 9 participants |
| Riluzole Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Drooling/Salivation | 2 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Increased Appetite | 8 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Hearing/Seeing Things | 2 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Trouble Sleeping | 24 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Nightmares | 15 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Drowsy | 25 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Nervousness | 19 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Fatigue | 26 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Irratibility | 22 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Poor Memory | 23 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Poor Concentration | 28 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Strange Feeling/Unreal | 7 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Abnormal Sensation | 5 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Numbness/Tingling | 8 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Dizziness | 10 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Headache | 14 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Blurred Vision | 8 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Ringing Ears | 9 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Stuffy Nose | 14 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Dry mouth | 10 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Drooling/Salivation | 4 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Muscle Cramp | 16 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Muscle Twitch | 10 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Trouble Sitting | 16 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Tremors/Shakiness | 9 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Poor Coordination | 11 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Slurred Speech | 5 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Rapid Heartbeat | 13 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Hyperventilation | 7 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Chest Pain | 6 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Nausea/Vomiting | 5 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Stomach Discomfort | 12 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Constipation | 5 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Diarrhea | 7 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Difficulty Urinating | 6 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Frequent Urination | 10 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Menstrual Irregularities | 2 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Loss of Sexual Interest | 26 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Sexual Performance Problems | 20 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Delayed/Absent Orgasm | 19 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Sweating Excessively | 10 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Fluid Retention | 6 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Decreased Appetite | 7 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Weight Gain | 8 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Weight Loss | 7 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Skin Rash | 4 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Diminished Mental Acuity | 22 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Difficulty Finding Words | 21 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Apathy Emotional Indifference | 18 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Dizzy When Standing Up | 10 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Bruising | 2 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Hair Thinning | 6 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Hot Flashes | 7 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Clenching Teeth | 13 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Strange Taste in Mouth | 8 participants |
| Riluzole/Placebo Addition to SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Unable to Sit Still | 17 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Sexual Performance Problems | 16 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Drooling/Salivation | 0 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Trouble Sleeping | 21 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Delayed/Absent Orgasm | 16 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Dry mouth | 10 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Bruising | 2 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Sweating Excessively | 14 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Stuffy Nose | 10 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Nervousness | 14 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Fluid Retention | 8 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Ringing Ears | 8 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Unable to Sit Still | 14 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Decreased Appetite | 8 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Blurred Vision | 5 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Headache | 13 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Increased Appetite | 15 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Dizziness | 4 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Hair Thinning | 8 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Weight Gain | 15 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Numbness/Tingling | 4 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Drowsy | 22 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Weight Loss | 7 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Abnormal Sensation | 3 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Strange Taste in Mouth | 5 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Skin Rash | 3 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Strange Feeling/Unreal | 5 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Hot Flashes | 12 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Diminished Mental Acuity | 22 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Poor Concentration | 25 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Chest Pain | 2 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Nightmares | 11 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Nausea/Vomiting | 3 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Hyperventilation | 3 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Difficulty Finding Words | 18 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Stomach Discomfort | 9 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Rapid Heartbeat | 9 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Poor Memory | 24 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Constipation | 10 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Slurred Speech | 3 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Hearing/Seeing Things | 1 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Diarrhea | 11 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Poor Coordination | 5 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Apathy Emotional Indifference | 21 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Difficulty Urinating | 1 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Tremors/Shakiness | 6 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Irratibility | 23 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Frequent Urination | 6 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Trouble Sitting | 14 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Clenching Teeth | 7 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Menstrual Irregularities | 1 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Muscle Twitch | 6 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Dizzy When Standing Up | 2 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Loss of Sexual Interest | 22 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Muscle Cramp | 12 participants |
| Placebo Addition to Standard SSRI Antidepressant | Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) | Fatigue | 28 participants |