Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, Depression
Brief summary
The purpose of this study was to evaluate the efficacy, safety, and tolerability of 2 fixed dose levels of vilazodone compared to placebo in patients with major depressive disorder.
Interventions
DRUGVilazodone
Vilazodone was supplied as film-coated tablets.
DRUGPlacebo to citalopram
Placebo to citalopram was supplied as a capsule.
DRUGPlacebo to vilazodone
Placebo to vilazodone was supplied as film-coated tablets.
DRUGCitalopram
Citalopram was supplied as encapsulated tablets.
Sponsors
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Men and women, 18-70 years of age. * Currently meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for Major Depressive Disorder. * The patient's current major depressive episode must be at least 8 weeks and no longer than 12 months in duration.
Exclusion criteria
* Women who are pregnant, women who will be breastfeeding during the study, and women of childbearing potential who are not practicing a reliable method of birth control. * Patients with a history of meeting DSM-IV-TR criteria for: * Any manic, hypomanic or mixed episode, including bipolar disorder and substance-induced manic, hypomanic, or mixed episode * Any depressive episode with psychotic or catatonic features * Panic disorder with or without agoraphobia * Obsessive-compulsive disorder * Schizophrenia, schizoaffective, or other psychotic disorder * Bulimia or anorexia nervosa * Presence of borderline personality disorder or antisocial personality disorder * Mental retardation, dementia, amnesia, or other cognitive disorders. * Patients who are considered a suicide risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 10 | Baseline to Week 10 | The MADRS is a clinician-rated scale based on participant interviews. The scale assesses depressive symptomatology that occurred in participants during the week preceding each interview. Participants were rated on 10 items: Apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item was scored on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score was the sum of the scores of the 10 items and ranged from 0 to 60. A higher score indicates more depressive symptomatology. A negative change score indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 10 in the Clinical Global Impressions-Severity (CGI-S) Scale Score | Baseline to Week 10 | The Clinical Global Impressions-Severity scale is a clinician-rated scale used to rate the severity of the participant's current state of mental illness compared with a patient population with major depressive disorder. In particular, the clinician is asked to respond to the following question: Considering your total clinical experience with this population, how mentally ill is the patient at this time? The patient is rated on the following 7-point scale: 1-normal, not at all ill, 2-borderline ill, 3-mildly ill, 4-moderately ill, 5-markedly ill, 6-severely ill, 7-among the most extremely ill patients. A higher score indicates more mental illness. A negative change score indicates improvement. |
| Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response | Baseline to Week 10 | The MADRS is a clinician-rated scale based on participant interviews. The scale assesses depressive symptomatology that occurred in participants during the week preceding each interview. Participants were rated on 10 items: Apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item was scored on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score was the sum of the scores of the 10 items and ranged from 0 to 60. A higher score indicates more depressive symptomatology. A MADRS sustained response was defined as a MADRS total score ≤ 12 for at least the last 2 visits during the double-blind treatment period (Weeks 1-10). A total MADRS score ≤ 12 corresponds to an average score of 1 per item and is indicative of very low level of depressive symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received 2 placebo to vilazodone tablets, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study. | 281 |
| Vilazodone 20 mg/Day Participants received 1 vilazodone tablet, 1 placebo to vilazodone tablet, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20 mg/day during Weeks 2 to 10, and vilazodone 10 mg/day during Week 11. | 288 |
| Vilazodone 40 mg/Day Participants received 1 placebo to vilazodone tablet, 1 vilazodone tablet, and 1 placebo to citalopram capsule orally once daily during Weeks 1 and 2 of the study. Participants received 2 vilazodone tablets and 1 placebo to citalopram capsule orally once daily during Weeks 3 -10 of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20/day mg during Week 2, and vilazodone 40 mg/day during Weeks 3 to 10. During Week 11, participants received vilazodone 20 mg/day for 4 days and 10 mg/day for 3 days. | 287 |
| Citalopram 40 mg/Day Participants received 2 placebo vilazodone tablets, and 1 citalopram capsule once daily for the 11 weeks of the study. Participants received citalopram 20 mg/day during Weeks 1 and 2, citalopram 40 mg/day during Weeks 3 to 10, and citalopram 20 mg/day during Week 11. | 282 |
| Total | 1,138 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 20 | 25 | 17 |
| Overall Study | Insufficient Therapeutic Response | 10 | 1 | 2 | 3 |
| Overall Study | Lost to Follow-up | 25 | 28 | 35 | 23 |
| Overall Study | Other Reasons | 0 | 0 | 1 | 3 |
| Overall Study | Protocol Violation | 17 | 23 | 19 | 17 |
| Overall Study | Withdrawal of Consent | 20 | 21 | 20 | 26 |
Baseline characteristics
| Characteristic | Placebo | Vilazodone 20 mg/Day | Vilazodone 40 mg/Day | Citalopram 40 mg/Day | Total |
|---|---|---|---|---|---|
| Age, Continuous | 42.0 years STANDARD_DEVIATION 13 | 41.7 years STANDARD_DEVIATION 12.7 | 40.8 years STANDARD_DEVIATION 13.2 | 42.6 years STANDARD_DEVIATION 12.6 | 41.8 years STANDARD_DEVIATION 12.8 |
| Age, Customized ≥ 20-29 years | 63 participants | 62 participants | 63 participants | 53 participants | 241 participants |
| Age, Customized < 20 years | 5 participants | 2 participants | 9 participants | 2 participants | 18 participants |
| Age, Customized ≥ 30-39 years | 48 participants | 59 participants | 68 participants | 59 participants | 234 participants |
| Age, Customized ≥ 40-49 years | 73 participants | 88 participants | 62 participants | 76 participants | 299 participants |
| Age, Customized ≥ 50-59 years | 66 participants | 50 participants | 62 participants | 66 participants | 244 participants |
| Age, Customized ≥ 60 years | 26 participants | 27 participants | 23 participants | 26 participants | 102 participants |
| Body Mass Index (BMI) | 28.70 kilograms per meter squared STANDARD_DEVIATION 5.4 | 28.79 kilograms per meter squared STANDARD_DEVIATION 5.49 | 28.45 kilograms per meter squared STANDARD_DEVIATION 5.43 | 28.36 kilograms per meter squared STANDARD_DEVIATION 5.17 | 28.58 kilograms per meter squared STANDARD_DEVIATION 5.37 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 59 Participants | 55 Participants | 43 Participants | 53 Participants | 210 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 222 Participants | 233 Participants | 244 Participants | 229 Participants | 928 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 167.60 cm | 167.60 cm | 168.90 cm | 169.00 cm | 168.50 cm |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 participants | 0 participants | 2 participants | 4 participants | 9 participants |
| Race/Ethnicity, Customized Asian | 7 participants | 7 participants | 3 participants | 3 participants | 20 participants |
| Race/Ethnicity, Customized Black or African American | 71 participants | 73 participants | 74 participants | 83 participants | 301 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 1 participants | 2 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized Other | 3 participants | 2 participants | 4 participants | 7 participants | 16 participants |
| Race/Ethnicity, Customized White | 197 participants | 205 participants | 202 participants | 184 participants | 788 participants |
| Sex: Female, Male Female | 158 Participants | 166 Participants | 164 Participants | 165 Participants | 653 Participants |
| Sex: Female, Male Male | 123 Participants | 122 Participants | 123 Participants | 117 Participants | 485 Participants |
| Weight | 82.27 kg STANDARD_DEVIATION 17.02 | 82.40 kg | 82.10 kg | 82.37 kg STANDARD_DEVIATION 18.3 | 82.41 kg STANDARD_DEVIATION 17.82 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 124 / 281 | 168 / 288 | 177 / 287 | 147 / 282 |
| serious Total, serious adverse events | 3 / 281 | 4 / 288 | 4 / 287 | 6 / 282 |
Outcome results
Primary
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 10
The MADRS is a clinician-rated scale based on participant interviews. The scale assesses depressive symptomatology that occurred in participants during the week preceding each interview. Participants were rated on 10 items: Apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item was scored on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score was the sum of the scores of the 10 items and ranged from 0 to 60. A higher score indicates more depressive symptomatology. A negative change score indicates improvement.
Time frame: Baseline to Week 10
Population: Intent-to-treat population: All randomized participants who received at least 1 dose of placebo, vilazodone, or citalopram and who had a baseline and at least 1 post-baseline assessment of the MADRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 10 | -14.76 Units on a scale | Standard Error 0.62 |
| Vilazodone 20 mg/Day | Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 10 | -17.33 Units on a scale | Standard Error 0.63 |
| Vilazodone 40 mg/Day | Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 10 | -17.58 Units on a scale | Standard Error 0.65 |
| Citalopram 40 mg/Day | Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 10 | -17.50 Units on a scale | Standard Error 0.64 |
p-value: 0.007395% CI: [-4.3, -0.84]Mixed-effect model
p-value: 0.003495% CI: [-4.57, -1.06]Mixed-effect model
p-value: 0.00295% CI: [-4.48, -1]Mixed-effect model
Secondary
Change From Baseline to Week 10 in the Clinical Global Impressions-Severity (CGI-S) Scale Score
The Clinical Global Impressions-Severity scale is a clinician-rated scale used to rate the severity of the participant's current state of mental illness compared with a patient population with major depressive disorder. In particular, the clinician is asked to respond to the following question: Considering your total clinical experience with this population, how mentally ill is the patient at this time? The patient is rated on the following 7-point scale: 1-normal, not at all ill, 2-borderline ill, 3-mildly ill, 4-moderately ill, 5-markedly ill, 6-severely ill, 7-among the most extremely ill patients. A higher score indicates more mental illness. A negative change score indicates improvement.
Time frame: Baseline to Week 10
Population: Intent-to-treat population: All randomized participants who received at least 1 dose of placebo, vilazodone, or citalopram and who had a baseline and at least 1 post-baseline assessment of the MADRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 10 in the Clinical Global Impressions-Severity (CGI-S) Scale Score | -1.53 Units on a scale | Standard Error 0.08 |
| Vilazodone 20 mg/Day | Change From Baseline to Week 10 in the Clinical Global Impressions-Severity (CGI-S) Scale Score | -1.88 Units on a scale | Standard Error 0.08 |
| Vilazodone 40 mg/Day | Change From Baseline to Week 10 in the Clinical Global Impressions-Severity (CGI-S) Scale Score | -1.86 Units on a scale | Standard Error 0.08 |
| Citalopram 40 mg/Day | Change From Baseline to Week 10 in the Clinical Global Impressions-Severity (CGI-S) Scale Score | -1.88 Units on a scale | Standard Error 0.08 |
p-value: 0.007395% CI: [-0.58, -0.13]Mixed-effect model
p-value: 0.009795% CI: [-0.55, -0.1]Mixed-effect model
p-value: 0.002595% CI: [-0.57, -0.12]Mixed-effect model
Secondary
Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response
The MADRS is a clinician-rated scale based on participant interviews. The scale assesses depressive symptomatology that occurred in participants during the week preceding each interview. Participants were rated on 10 items: Apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item was scored on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score was the sum of the scores of the 10 items and ranged from 0 to 60. A higher score indicates more depressive symptomatology. A MADRS sustained response was defined as a MADRS total score ≤ 12 for at least the last 2 visits during the double-blind treatment period (Weeks 1-10). A total MADRS score ≤ 12 corresponds to an average score of 1 per item and is indicative of very low level of depressive symptoms.
Time frame: Baseline to Week 10
Population: Intent-to-treat population: All randomized participants who received at least 1 dose of placebo, vilazodone, or citalopram and who had a baseline and at least 1 post-baseline assessment of the MADRS total score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response | 26.3 Percentage of participants |
| Vilazodone 20 mg/Day | Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response | 29.9 Percentage of participants |
| Vilazodone 40 mg/Day | Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response | 33.5 Percentage of participants |
| Citalopram 40 mg/Day | Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response | 31.1 Percentage of participants |
p-value: 0.356395% CI: [-3.9, 10.9]Cochran-Mantel-Haenszel
p-value: 0.161195% CI: [-0.4, 14.6]Cochran-Mantel-Haenszel
p-value: 0.267295% CI: [-2.7, 12.2]Cochran-Mantel-Haenszel