Antidepressant Response in the Treatment of Depressive Symptoms and Frailty Characteristics in Older Adults
Condition: Major Depressive Disorder; Dysthymic Disorder; Depressive Disorder, NOS
MeSH terms: Frailty; Depressive Disorder; Depression; Depressive Disorder, Major; Dysthymic Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      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).
    

Detailed description: 
      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.
    

Intervention name(s): Antidepressant Medication
Intervention type(s): Drug
Intervention description(s): If patient has a history of non-response or cannot tolerate escitalopram and/or duloxetine, then they will be treated openly with an approved antidepressant.
Other intervention name(s): Escitalopram; Duloxetine; Open treatment
Intervention MeSH terms: Duloxetine Hydrochloride; Antidepressive Agents; Escitalopram
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment