Major Depressive Disorder
Conditions
Keywords
depressed, older adults, antidepressants, depression, MDD
Brief summary
The purpose of this study is to examine the effects of levomilnacipran (FETZIMA) compared to placebo for the treatment of depression in older adults.
Detailed description
A 12-week pilot double-blind comparison of levomilnacipran (FETZIMA) to placebo for the treatment of geriatric depression. The investigators are interested in assessing the efficacy of levomilnacipran (LMIL) to placebo (PBO), and exploring the effects of antidepressant response on brain connectivity and neuroplasticity. This pilot study is designed to determine any differences in the efficacy, safety and tolerability of levomilnacipran compared to placebo, and to perform dose finding (20-120 mg per day) in 40 older depressed adults. The investigators anticipate that the LMIL will be superior to PBO in improving levels of depressive symptoms and rates of remission, as well as improving cognition, apathy, and quality of life. This proposal expands the investigator's focus on the biomarkers of neuroplasticity that have been used in several prior studies and demonstrated responsivity to antidepressant treatment. The purpose is to examine this directly in 40 older adults with major depression. This proposed trial will also serve as a pilot study to estimate the efficacy and tolerability of the drug in older depressed adults, and the dose-finding in this population.
Interventions
DRUGlevomilnacipran
antidepressant
DRUGPlacebo
an inactive drug
Sponsors
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 and Mental Disorders, 5th edition (DSM-V) criteria * A 24-item Hamilton Rating Scale for Depression (HAMD) score of 16 or higher at baseline * Mini-Mental State Exam (MMSE) score \> 24.
Exclusion criteria
Subjects will be excluded if they had 1) any current and/or lifetime history of other psychiatric disorders (except unipolar depression with or without comorbid generalized anxiety disorder), or 2) recent unstable medical or neurological disorders; 3) any disabilities preventing participation in the study or in the MRI; 4) diagnosis of dementia; 5) acute suicidality; 6) subjects with known allergic reactions to milnacipran, uncontrolled narrow angle glaucoma, seizures, poorly-controlled hypertension or ischemic changes on ECG, serotonin syndrome, or the recently used monoamine oxidase inhibitors (MAOIs) within last 4 weeks; 7) ineligible for MRI (e.g., metal in the body or claustrophobia)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale (HDRS) Scores 24 | Baseline and 12 weeks | This measure includes 24 items. Response options vary item to item and include the following ranges: \[0-2\], \[0-3\], and \[0-4\]. A score of 0 suggests absence of symptoms and/or difficulties and higher scores represent more severe difficulties. Possible overall score range \[0-74\], higher scores representing more severe difficulties. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression Scale (CGI) Scores | Week 12 reported | 7-Point Likert Scale \[1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse\]. |
| Geriatric Depression (GDS) Scores | Baseline and 12 weeks | The GDS has a total of 30 items with response options \[Yes/No\]. Total score range is \[0-30\]. Higher scores represent more severe difficulties. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Levomilnacipran (FETZIMA) All eligible subjects will be randomized to levomilnacipran or placebo 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.
levomilnacipran: antidepressant | 17 |
| Placebo All eligible subjects will be randomized to levomilnacipran or placebo 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.
Placebo: an inactive drug | 12 |
| Total | 29 |
Baseline characteristics
| Characteristic | Levomilnacipran (FETZIMA) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 8 Participants | 25 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 4 Participants | 4 Participants |
| Age, Continuous | 73.24 years STANDARD_DEVIATION 4.6 | 69.08 years STANDARD_DEVIATION 6.6 | 71.5 years STANDARD_DEVIATION 5.8 |
| Hamilton Depression Rating Scale Score | 17.88 units on a scale STANDARD_DEVIATION 2.5 | 19.92 units on a scale STANDARD_DEVIATION 2.6 | 18.7 units on a scale STANDARD_DEVIATION 2.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 16 Participants | 8 Participants | 24 Participants |
| Region of Enrollment United States | 17 Participants | 12 Participants | 29 Participants |
| Sex: Female, Male Female | 10 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Male | 7 Participants | 4 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 12 |
| other Total, other adverse events | 11 / 17 | 2 / 12 |
| serious Total, serious adverse events | 0 / 17 | 0 / 12 |
Outcome results
Primary
Hamilton Depression Rating Scale (HDRS) Scores 24
This measure includes 24 items. Response options vary item to item and include the following ranges: \[0-2\], \[0-3\], and \[0-4\]. A score of 0 suggests absence of symptoms and/or difficulties and higher scores represent more severe difficulties. Possible overall score range \[0-74\], higher scores representing more severe difficulties.
Time frame: Baseline and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levomilnacipran (FETZIMA) | Hamilton Depression Rating Scale (HDRS) Scores 24 | 12 Weeks | 6.86 units on a scale | Standard Deviation 5.7 |
| Levomilnacipran (FETZIMA) | Hamilton Depression Rating Scale (HDRS) Scores 24 | Baseline | 17.88 units on a scale | Standard Deviation 2.5 |
| Placebo | Hamilton Depression Rating Scale (HDRS) Scores 24 | 12 Weeks | 10.33 units on a scale | Standard Deviation 7.1 |
| Placebo | Hamilton Depression Rating Scale (HDRS) Scores 24 | Baseline | 19.92 units on a scale | Standard Deviation 2.6 |
Secondary
Clinical Global Impression Scale (CGI) Scores
7-Point Likert Scale \[1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse\].
Time frame: Week 12 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levomilnacipran (FETZIMA) | Clinical Global Impression Scale (CGI) Scores | 3.00 units on a scale | Standard Deviation 0.81 |
| Placebo | Clinical Global Impression Scale (CGI) Scores | 3.33 units on a scale | Standard Deviation 1.11 |
Secondary
Geriatric Depression (GDS) Scores
The GDS has a total of 30 items with response options \[Yes/No\]. Total score range is \[0-30\]. Higher scores represent more severe difficulties.
Time frame: Baseline and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levomilnacipran (FETZIMA) | Geriatric Depression (GDS) Scores | Baseline | 13.5 units on a scale | Standard Deviation 4 |
| Levomilnacipran (FETZIMA) | Geriatric Depression (GDS) Scores | 12 Weeks | 11.71 units on a scale | Standard Deviation 5.6 |
| Placebo | Geriatric Depression (GDS) Scores | Baseline | 15.33 units on a scale | Standard Deviation 4.8 |
| Placebo | Geriatric Depression (GDS) Scores | 12 Weeks | 11.33 units on a scale | Standard Deviation 3.6 |