Trial of Levomilnacipran in Geriatric Depression

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.

Inclusion Criteria:

- 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 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 MAOIs within last 4 weeks; 7)
ineligible for MRI (e.g., metal in the body or claustrophobia)