The purpose of this study is to examine the effects of levomilnacipran (FETZIMA) compared to
placebo for the treatment of depression in older adults.
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 60
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 60 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.
- 60 years of age or older
- The presence of a major depressive disorder diagnosed according to the DSM-V criteria
- A 24-item Hamilton Rating Scale for Depression (HAMD) score of 17 or higher at
- Mini-Mental State Exam (MMSE) score > 24.
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 MAOIs within last 4 weeks; 7)
ineligible for MRI (e.g., metal in the body or claustrophobia)
Helen Lavretsky, M.D.
University of California, Los Angeles
Helen Lavretsky, M.D.