Major Depressive Disorder
Conditions
Keywords
Vilazodone, Citalopram, Major Depressive Disorder
Brief summary
The purpose of this study is to evaluate the safety and effectiveness of vilazodone for the treatment of major depressive disorder versus citalopram. Doctors want to determine if vilazodone is effective for the treatment of major depressive disorder in those who have not responded to generic selective serotonin reuptake inhibitors (SSRI), which is a class of anti-depressant drugs such as Prozac, Lexapro, Paxil, or Zoloft. Both vilazodone and citalopram have been approved for the treatment of major depressive disorder. This research is being done because the researchers want to find out if vilazodone works in reducing the symptoms of depression significantly more than a generic SSRI.
Detailed description
The goal of the proposed study is to evaluate the efficacy and safety of switching to Vilazodone in patients with major depressive disorder (MDD) who are unresponsive to, only partially responsive to, or cannot tolerate a trial of the generic SSRI, citalopram (e.g., partially responsive means patients who report that their depressive symptoms have improved through the use of citalopram but that significant depressive symptoms persist; cannot tolerate refers to patient report of intolerable side effects that result in a desire to discontinue the medication). Seventy-two subjects with major depressive disorder who are still symptomatic or report intolerable side effects after a 6-week open-label trial of citalopram 20mg/day ( i.e. who are not classified as responders) will be randomized to receive a higher maximum dose of citalopram (40mg/day) or switch to vilazodone during the randomization phase of the trial for 6 weeks. The hypothesis to be tested is that vilazodone will result in greater rates of treatment response and be better tolerated compared to being titrated up to a higher maximum dose (40mg/day) of citalopram. The proposed study will provide needed data on the efficacy of switching antidepressants when individuals do not fully respond to previous treatment or have intolerable side effects with a generic SSRI.
Interventions
DRUGVilazodone
A fixed dose titration (with doses ranging from 10mg to 40mg/day) will be used. Subjects will take 10mg/day for 1 week, 20mg/day for 1 week and then 40mg/day.
DRUGCitalopram
For those assigned to citalopram, the dose of citalopram will be maximized to 40mg/day. For those assigned to vilazodone, their citalopram dose will be maintained at 20mg/day for 1 week, then reduced to 10mg/day for 1 week, then switched to vilazodone 10mg/day.
Sponsors
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women age 18-60; 2. Primary diagnosis of MDD. Diagnosis of MDD will be made with the Structured Clinical Interview for DSM-IV 3. Score of at least 23 on the Montgomery-Åsberg Depression Rating Scale 4. Treatment with citalopram at a dose no higher than 20mg/day for no longer than 4 weeks (subjects not currently taking an antidepressant will be started on citalopram 20mg/day for the 6-week open-label phase) 5. Ability to understand and sign the consent form.
Exclusion criteria
1. Unstable medical illness based on history or clinically significant abnormalities on baseline physical examination (e.g., congestive heart failure, bradyarrhythmias). 2. Current pregnancy or lactation, or inadequate contraception in women of childbearing potential 3. Subjects considered an immediate suicide risk based on the Columbia Suicide Severity rating Scale (C-SSRS) 4. Past 3-month DSM-IV substance abuse or dependence 5. Illegal substance use based on urine toxicology screening 6. Initiation of psychotherapy or behavior therapy specifically for MDD from a mental health professional within 3 months prior to study baseline 7. Initiation of any other psychotropic medication within 2 months prior to study inclusion 8. Concomitant use of any antidepressant (except low dose doxepin, amitriptyline, trazodone when used PRN as a hypnotic). 9. Concomitant use of medications that prolong the QT interval or are CYP2C19 inhibitors (e.g., cimetidine) 10. Previous treatment with vilazodone 11. Diagnosis of bipolar I or II disorder or any psychotic disorder (anxiety disorders will be allowed as long as MDD is considered the primary psychiatric disorder) 12. Cognitive impairment that interferes with the capacity to understand and self-administer medication or provide written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Åsberg Depression Rating Scale (MADRS) | Baseline and final MADRS scores during the double-blind phase. | The entire study will last 18 weeks. For the first 6 weeks, subjects will come in once every 2 weeks. For the next 4 weeks, subjects will come in once per week. For the next 6 weeks, subjects will come in once every 2 weeks. The final visit will come 2 weeks later for a total of 11 visits where the MADRS will be administered. Only the baseline and final (last observation) assessments for the outcome measure was used in determining results, thus these are the only values included. MADRS scores range from 0-60, with higher scores indicating a greater level of severity. No subscales were used. |
Countries
United States
Participant flow
Recruitment details
The Enrollment number in the Protocol Section (79) conflicts with the number of participants Started in the Participant Flow module (48) because the assessment of interested was the double-blind portion of the study. Only 48 subjects were enrolled in this phase of the study, while 79 were enrolled in the preliminary open-label phase.
Pre-assignment details
The results reported are for the double-blind phase, not the open label citalopram phase of the study.
Participants by arm
| Arm | Count |
|---|---|
| Vilazodone A fixed dose titration (with doses ranging from 10mg to 40mg/day) will be used. Subjects will take 10mg/day for 1 week, 20mg/day for 1 week and then 40mg/day.
Vilazodone: A fixed dose titration (with doses ranging from 10mg to 40mg/day) will be used. Subjects will take 10mg/day for 1 week, 20mg/day for 1 week and then 40mg/day. | 19 |
| Citalopram For those assigned to citalopram, the dose of citalopram will be maximized to 40mg/day. For those assigned to vilazodone, their citalopram dose will be maintained at 20mg/day for 1 week, then reduced to 10mg/day for 1 week, then switched to vilazodone 10mg/day.
Citalopram: For those assigned to citalopram, the dose of citalopram will be maximized to 40mg/day. For those assigned to vilazodone, their citalopram dose will be maintained at 20mg/day for 1 week, then reduced to 10mg/day for 1 week, then switched to vilazodone 10mg/day. | 23 |
| Total | 42 |
Baseline characteristics
| Characteristic | Citalopram | Vilazodone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 19 Participants | 42 Participants |
| Age, Continuous | 38.6 years STANDARD_DEVIATION 11.1 | 31.7 years STANDARD_DEVIATION 11.3 | 35.4 years STANDARD_DEVIATION 11.6 |
| Region of Enrollment United States | 23 Participants | 19 Participants | 42 Participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 21 Participants |
| Sex: Female, Male Male | 13 Participants | 8 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 19 | 1 / 23 |
| serious Total, serious adverse events | 0 / 19 | 0 / 23 |
Outcome results
Primary
Montgomery-Åsberg Depression Rating Scale (MADRS)
The entire study will last 18 weeks. For the first 6 weeks, subjects will come in once every 2 weeks. For the next 4 weeks, subjects will come in once per week. For the next 6 weeks, subjects will come in once every 2 weeks. The final visit will come 2 weeks later for a total of 11 visits where the MADRS will be administered. Only the baseline and final (last observation) assessments for the outcome measure was used in determining results, thus these are the only values included. MADRS scores range from 0-60, with higher scores indicating a greater level of severity. No subscales were used.
Time frame: Baseline and final MADRS scores during the double-blind phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vilazodone | Montgomery-Åsberg Depression Rating Scale (MADRS) | First Randomized Visit (Visit 8) | 13.9 units on a scale | Standard Deviation 5.3 |
| Vilazodone | Montgomery-Åsberg Depression Rating Scale (MADRS) | Second Randomized Visit (Visit 9) | 14.5 units on a scale | Standard Deviation 4.4 |
| Vilazodone | Montgomery-Åsberg Depression Rating Scale (MADRS) | Third Randomized Visit (Visit 10) | 13.9 units on a scale | Standard Deviation 5.1 |
| Vilazodone | Montgomery-Åsberg Depression Rating Scale (MADRS) | Fourth Randomized Visit (Visit 11) | 13.9 units on a scale | Standard Deviation 5.3 |
| Citalopram | Montgomery-Åsberg Depression Rating Scale (MADRS) | Fourth Randomized Visit (Visit 11) | 12.7 units on a scale | Standard Deviation 8.4 |
| Citalopram | Montgomery-Åsberg Depression Rating Scale (MADRS) | First Randomized Visit (Visit 8) | 12.7 units on a scale | Standard Deviation 8.4 |
| Citalopram | Montgomery-Åsberg Depression Rating Scale (MADRS) | Third Randomized Visit (Visit 10) | 13.5 units on a scale | Standard Deviation 8.5 |
| Citalopram | Montgomery-Åsberg Depression Rating Scale (MADRS) | Second Randomized Visit (Visit 9) | 13.2 units on a scale | Standard Deviation 8.5 |
p-value: 0.342Regression, Linear