Antidepressant Response in the Treatment of Depressive Symptoms and Frailty Characteristics in Older Adults

The goal of this open-administration treatment study of citalopram (or duloxetine) is to evaluate the effect of antidepressant medication on treating the syndrome of "frailty" in older adults with depressive symptoms. Patients with significant depressive symptoms (defined as CES-D (Center for Epidemiological Studies - Depression scale) \> 10) and 1 or more symptoms of the frailty syndrome (exhaustion, decreased energy, weight loss, decreased grip strength, and slow/unsteady gait) will be evaluated and treated with citalopram (or duloxetine) for 8 weeks to test whether antidepressant medication improves both the syndrome of frailty and depressive symptoms. Patients evaluated at the Adult and Late Life Depression clinic and eligible to participate in the study will be treated with an antidepressant medication and assessed on the primary outcome variables (characteristics of frailty, depressive symptoms) as well as on secondary variables which include cognition (global cognition, episodic memory, executive function), and function (physical mobility, instrumental activities of daily living, and social functioning) prior to treatment initiation and following 8-weeks of treatment. The hypotheses for this protocol predict that we will discover a significant improvement on both frailty characteristics and depressive symptoms in this clinical population when treated with antidepressant medication (citalopram or duloxetine).

Frailty, "a syndrome of decreased resiliency and reserves", is defined by five characteristics: 1)"shrinking" (definition: unintentional weight loss of \> 10 lbs in prior year, or \> 5% loss of body weight in prior year at follow-up), 2) weakness (definition: grip strength in lowest 20% at baseline, adjusted for gender and BMI), 3) poor endurance/energy (definition: self-report of exhaustion on 2 items on the CES-D), 4) slowness (definition: slowest 20% on timed 4 meter or 15 foot walk, adjusted for gender and standing height), and 5) low physical activity (definition: weighted score of kilocalories expended per week as calculated from the Minnesota Leisure Time Activity questionnaire). Frailty is associated with poor prognosis including hospitalization, falls, worsening disability and mobility, and death.

Data from the Cardiovascular Health Study document the rate of comorbid depressive symptoms in frail older adults (16.2% of older adults with at least 1 frailty characteristic had a CES-D \> 10, including 31% of older adults with 3 or more frailty characteristics, compared to 2.6% of nonfrail older adults) despite study exclusion of individuals who were taking an antidepressant (this is in part why we chose to include patients with a CES-D of \> 10, rather than requiring a diagnosis of a depressive disorder such as major depression or dysthymia for this study). The relationship between frailty and depression however goes beyond this association; the five defining characteristics of frailty (exhaustion, decreased energy, weight loss, decreased grip strength, and slow/unsteady gait) overlap significantly with symptoms of geriatric depression (decreased energy and motivation, psychomotor slowing, weight loss, decreased participation in leisure activities).

The proposed study is innovative in that it is focuses on a group of older adults who have been unrepresented (via exclusion criteria) in previous clinical studies (frail older adults with comorbid depressive symptoms), and it treats the comorbid depressive symptoms and targets characteristics of the frailty syndrome in the hopes of altering the prognostic trajectory of this clinical sample. This protocol serves two purposes: 1. It tests the feasibility of recruiting and retaining frail older adults with depressive symptoms in a treatment trial, and 2. It provides pilot data for the effectiveness of an antidepressant medication on treating the characteristics of frailty and the comorbid depressive symptoms.

Eligibility Criteria:
Inclusion Criteria:

* Anyone with 1 or more characteristics of frailty
* HRSD\>16 and a DSM-IV depressive disorder (e.g. MDD, Dysthymia)
* Capable of providing informed consent
* Currently followed by a PCP (had an eval in last 6-months)

Exclusion Criteria:

* Acute cancer treatment
* Acute, severe or unstable medical illness
* End stage medical illness (e.g. liver, kidney, pulmonary)
* Mini Mental Exam \< 24 or a diagnosis of dementia
* Individuals who do not have capacity to consent
* Diagnosis of substance abuse or dependence (last 12 months), excluding Nicotine dependence
* History of psychosis or psychotic disorder or bipolar disorder
* Patient is considered a significant risk of suicide
* Subject is considered based on history to be unlikely to respond to the single agent antidepressant (i.e., subjects with treatment resistant depression, including subjects with previous treatment with ECT)
* History of allergic or adverse reaction to escitalopram or duloxetine, or non-response to adequate trial of escitalopram (at least 4 weeks at dose of 20 mg) or duloxetine (at least 4 weeks at dose of 90mg).