Major Depressive Disorder
Conditions
Keywords
depressed, geriatric, older adults, antidepressants, depression, anxious, major depressive disorder, MDD
Brief summary
The purpose of this study is to examine the effects of vilazodone for the treatment of depression in older adults.
Detailed description
This is a 12-week double-blind comparison of a novel antidepressant, vilazodone, to the gold-standard drug, paroxetine, for the treatment of geriatric depression. We are interested in assessing the difference in response to vilazodone (VLZ) compared to paroxetine (PAR). We hope to detect difference in response in primary outcomes (depressed mood) and secondary outcomes cognition. We are seeking to examine this directly in 80 older adults (60 years of age or older) with major depression with anticipated 60 completers. This proposed trial will serve as a pilot study to estimate the efficacy and tolerability of the drug in older depressed adults, and use this project for dose-finding in this population.
Interventions
DRUGVilazodone; Viibryd
Subjects randomized to receive vilazodone blindly will have incremental dose titration of 10mg per day for the 1st week; 20mg per day the 2nd week; 40mg per day for the 3rd-12th week. Doses of the drugs will be adjusted according to individual tolerability and safety.
DRUGParoxetine; Paxil
Subjects randomized to receive paroxetine blindly will have incremental dose titration of paroxetine 10mg per day for the 1st week; 20mg per day for the 2nd week; and 30mg per day for the 3rd-12 week. Doses of the drugs will be adjusted according to individual tolerability and safety.
Sponsors
Forest Laboratories
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 60 years of age or older * The presence of a major depressive disorder diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria * A 24-item Hamilton Depression Rating Scale (HAMD) score of 17 or higher at baseline * Mini-Mental State Exam (MMSE) score \> 24.
Exclusion criteria
* Subjects will be excluded if they had any current and/or lifetime history of other psychiatric disorders (except unipolar depression with or without comorbid generalized anxiety disorder), or recent unstable medical or neurological disorders; any disabilities preventing their participation in the study; diagnosis of mild cognitive impairment (MCI)/dementia; those with known allergic reactions to paroxetine or vilazodone.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale (HDRS) | Baseline and 12 weeks | The HAMD measures the severity of depressive symptoms in participants with major depressive disorder (MDD). It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| UKU Side-effect Profile | Each visit for 12 weeks | Number of participants with each side-effect event. |
| Neurocognitive Measure: The Rey-Osterrieth Complex Figure Test | Baseline and Final Visit | The The Rey-Osterrieth Complex Figure Test (REY-O) is a neuropsychological assessment in which measures visual perception and long-term visual memory. Total raw scores range from 0 to 36 with higher scores representing better outcomes in recall. The total raw score represents a sum of subscales scored by 18 individual elements which are scored for both distortion and placement. Two points are awarded to elements that are accurately drawn and properly placed, one point is given to distorted or misplaced elements, 0.5 points are given if an element is both distorted and misplaced, and missing or unrecognizable elements receive zero points. |
| Changes in Proinflammatory Gene Expression From Baseline to Final Visit (up to 12 Weeks) | Baseline and Final Visit | Gene expression data were quantile-normalized and log2-transformed in RNA expression units. The measure included the promoter transcription factor binding motif prevalence ratio of the unit (log2 Vilazodone/Paroxetine) and ranging from a minimum of -3 to a maximum of 3 with higher scores indicating better outcomes. |
Countries
United States
Participant flow
Recruitment details
Single site outpatient clinic in the U.S.
Pre-assignment details
208 volunteers were assessed for eligibility, of which 100 declined to participate and 37 did not meet inclusion criteria. Seventy-one persons consented to participate, of which 65 passed screening and were enrolled; nine of 65 enrolled participants withdrew before randomization.
Participants by arm
| Arm | Count |
|---|---|
| Vilazodone; Viibryd After screening and baseline test results are reviewed and eligibility criteria are confirmed, medications will be dispensed if patients continue to meet eligibility criteria and sign the informed consent form. All eligible subjects will be randomized to vilazodone or paroxetine group using a computer-generated random assignment scheme, which assigned subjects in a 1:1 ratio to each group. Randomization will be done prior to subject's being assigned to the groups. Doses of the drugs will be adjusted according to individual tolerability and safety.
Vilazodone; Viibryd: Subjects randomized to receive vilazodone blindly will have incremental dose titration of 10mg per day for the 1st week; 20mg per day the 2nd week; 40mg per day for the 3rd-12th week. Doses of the drugs will be adjusted according to individual tolerability and safety. | 26 |
| Paroxetine; Paxil After screening and baseline test results are reviewed and eligibility criteria are confirmed, medications will be dispensed if patients continue to meet eligibility criteria and sign the informed consent form. All eligible subjects will be randomized to vilazodone or paroxetine group using a computer-generated random assignment scheme, which assigned subjects in a 1:1 ratio to each group. Randomization will be done prior to subject's being assigned to the groups. Doses of the drugs will be adjusted according to individual tolerability and safety.
Paroxetine; Paxil: Subjects randomized to receive paroxetine blindly will have incremental dose titration of paroxetine 10mg per day for the 1st week; 20mg per day for the 2nd week; and 30mg per day for the 3rd-12 week. Doses of the drugs will be adjusted according to individual tolerability and safety. | 30 |
| Total | 56 |
Baseline characteristics
| Characteristic | Paroxetine; Paxil | Vilazodone; Viibryd | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 21 Participants | 42 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 5 Participants | 14 Participants |
| Age, Continuous | 71.5 years STANDARD_DEVIATION 7.7 | 71.5 years STANDARD_DEVIATION 7.2 | 71.5 years STANDARD_DEVIATION 7.4 |
| Region of Enrollment United States | 30 participants | 26 participants | 56 participants |
| Sex: Female, Male Female | 13 Participants | 13 Participants | 26 Participants |
| Sex: Female, Male Male | 17 Participants | 13 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 26 | 16 / 30 |
| serious Total, serious adverse events | 0 / 26 | 0 / 30 |
Outcome results
Primary
Hamilton Depression Rating Scale (HDRS)
The HAMD measures the severity of depressive symptoms in participants with major depressive disorder (MDD). It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms.
Time frame: Baseline and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vilazodone; Viibryd | Hamilton Depression Rating Scale (HDRS) | HDRS Baseline | 17.2 units on a scale | Standard Deviation 3.7 |
| Vilazodone; Viibryd | Hamilton Depression Rating Scale (HDRS) | HDRS Final Visit | 7.6 units on a scale | Standard Deviation 4.8 |
| Paroxetine; Paxil | Hamilton Depression Rating Scale (HDRS) | HDRS Final Visit | 7.5 units on a scale | Standard Deviation 5.9 |
| Paroxetine; Paxil | Hamilton Depression Rating Scale (HDRS) | HDRS Baseline | 16.6 units on a scale | Standard Deviation 4.1 |
Secondary
Changes in Proinflammatory Gene Expression From Baseline to Final Visit (up to 12 Weeks)
Gene expression data were quantile-normalized and log2-transformed in RNA expression units. The measure included the promoter transcription factor binding motif prevalence ratio of the unit (log2 Vilazodone/Paroxetine) and ranging from a minimum of -3 to a maximum of 3 with higher scores indicating better outcomes.
Time frame: Baseline and Final Visit
Population: The Arms/Groups are not combined, but results are presented as a ratio of Vilazodone/Paroxetine.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vilazodone; Viibryd | Changes in Proinflammatory Gene Expression From Baseline to Final Visit (up to 12 Weeks) | AP-1, Activator Protein | -0.8 RNA expression units | Standard Error 0.5 |
| Vilazodone; Viibryd | Changes in Proinflammatory Gene Expression From Baseline to Final Visit (up to 12 Weeks) | NF-kB, Nuclear Factor Kappa B | -1.25 RNA expression units | Standard Error 0.5 |
| Vilazodone; Viibryd | Changes in Proinflammatory Gene Expression From Baseline to Final Visit (up to 12 Weeks) | GR, Glucocorticoid Receptor | 0.2 RNA expression units | Standard Error 0.6 |
| Vilazodone; Viibryd | Changes in Proinflammatory Gene Expression From Baseline to Final Visit (up to 12 Weeks) | CREB, cAMP response element binding protein | -2.1 RNA expression units | Standard Error 0.7 |
Secondary
Neurocognitive Measure: The Rey-Osterrieth Complex Figure Test
The The Rey-Osterrieth Complex Figure Test (REY-O) is a neuropsychological assessment in which measures visual perception and long-term visual memory. Total raw scores range from 0 to 36 with higher scores representing better outcomes in recall. The total raw score represents a sum of subscales scored by 18 individual elements which are scored for both distortion and placement. Two points are awarded to elements that are accurately drawn and properly placed, one point is given to distorted or misplaced elements, 0.5 points are given if an element is both distorted and misplaced, and missing or unrecognizable elements receive zero points.
Time frame: Baseline and Final Visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vilazodone; Viibryd | Neurocognitive Measure: The Rey-Osterrieth Complex Figure Test | REY-O 3 Minute Delay Baseline | 13.3 units on a scale | Standard Deviation 5.9 |
| Vilazodone; Viibryd | Neurocognitive Measure: The Rey-Osterrieth Complex Figure Test | REY-O 3 Minute Delay Final Visit | 15.2 units on a scale | Standard Deviation 7.4 |
| Paroxetine; Paxil | Neurocognitive Measure: The Rey-Osterrieth Complex Figure Test | REY-O 3 Minute Delay Baseline | 13.3 units on a scale | Standard Deviation 5.3 |
| Paroxetine; Paxil | Neurocognitive Measure: The Rey-Osterrieth Complex Figure Test | REY-O 3 Minute Delay Final Visit | 16.3 units on a scale | Standard Deviation 4.8 |
Secondary
UKU Side-effect Profile
Number of participants with each side-effect event.
Time frame: Each visit for 12 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vilazodone; Viibryd | UKU Side-effect Profile | Concentration Difficulties | 3 participants |
| Vilazodone; Viibryd | UKU Side-effect Profile | Sedation | 1 participants |
| Vilazodone; Viibryd | UKU Side-effect Profile | Increased dream activity | 3 participants |
| Vilazodone; Viibryd | UKU Side-effect Profile | Reduced salivation | 3 participants |
| Vilazodone; Viibryd | UKU Side-effect Profile | Diarrhea | 3 participants |
| Vilazodone; Viibryd | UKU Side-effect Profile | Constipation | 3 participants |
| Vilazodone; Viibryd | UKU Side-effect Profile | Orthostatic dizziness | 3 participants |
| Paroxetine; Paxil | UKU Side-effect Profile | Reduced salivation | 1 participants |
| Paroxetine; Paxil | UKU Side-effect Profile | Concentration Difficulties | 0 participants |
| Paroxetine; Paxil | UKU Side-effect Profile | Constipation | 5 participants |
| Paroxetine; Paxil | UKU Side-effect Profile | Sedation | 3 participants |
| Paroxetine; Paxil | UKU Side-effect Profile | Diarrhea | 1 participants |
| Paroxetine; Paxil | UKU Side-effect Profile | Increased dream activity | 3 participants |
| Paroxetine; Paxil | UKU Side-effect Profile | Orthostatic dizziness | 3 participants |