Memantine Plus Es-citalopram in Elderly Depressed Patients With Cognitive Impairment
Condition: Mild Cognitive Impairment; Major Depressive Disorder; Alzheimer's Disease
MeSH terms: Alzheimer Disease; Depressive Disorder; Cognitive Dysfunction; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Alzheimer's disease (AD), the most common dementing disorder of later life, is a major cause
      of disability and death in the elderly. Although a number of theoretical causes exist, the
      etiology of AD is still unknown. Consequently, the focus of treatments has been palliative,
      designed to ameliorate AD symptoms. Recent efforts, however, have revealed some surprising
      data suggesting that cholinesterase inhibitors (AchEIs), used over the last decade, and
      recently released memantine (an N-methyl-D-aspartate (NMDA) receptor antagonist), may confer
      protection to neurons. Thus, they may offer a slowing of cognitive decline and/or improvement
      in behavioral symptoms associated with memory impairment.

      Over the last decade, it has been well documented that mild cognitive impairment (MCI)
      increases the risk of conversion to AD and that coincident depression and MCI (Dep-MCI)
      further increases the risk 2 to 3 fold. The primary focus of this line of investigation is to
      treat the very high risk to dement patient population with Dep-MCI, before they develop AD,
      in the hopes of delaying AD onset.

      Memantine had not been studied in DEP-MCI patients. Since treatment of these patients with
      combined antidepressant and AChEIs has been associated with cognitive improvement in pilot
      studies, we explore whether treatment of DEP-MCI with memantine in addition to antidepressant
      treatment would benefit cognitive performance and lead to a low rate of conversion to
      dementia. We evaluate the cognitive and antidepressant benefit of combined open-label
      es-citalopram and memantine treatment over 48 weeks in a DEP-CI sample.
    

Detailed description: 
      The study is conducted in a sample of 35 elderly (50-90 years old) outpatients who meet study
      inclusion criteria for depression (DEP) (DSM-IV criteria for major depression, dysthymic
      disorder, or depression NOS) and mild cognitive impairment (MCI; e.g. operationally defined
      as between "normal" and "dementia"), i.e., Dep-MCI. The research plan includes: i) Obtaining
      a baseline psychiatric and neuropsychological test profile, ii) If currently on an
      ineffective antidepressant, having a one week washout (3 weeks for fluoxetine), iii) A
      treatment trial beginning with a two-week es-citalopram lead-in period. At two weeks,
      memantine (Namenda) is added starting at 5 mg/day and increased until the maximum dose of 20
      mg/day is reached by six weeks. The study psychiatrist administers: the 24-item Hamilton
      Depression Rating Scale (HAM-D); the Clinical Global Impression (CGI, 1-7 scale) initial
      severity and subsequent change ratings separately for depression, cognition, and overall
      clinical status; the Treatment Emergent Symptom Scale (TESS) for somatic side effects. A
      trained technician administers the neuropsychological battery at baseline, 12, 24 and 48
      weeks. If the patient is an antidepressant non-responder during the first 12-weeks, the
      es-citalopram is changed to an alternative antidepressant, as clinically indicated by the
      treating psychiatrist. The patient remains on the memantine for the entire 48-weeks,
      irrespective of antidepressant response.

      This will tell us about the efficacy and tolerability of es-citalopram+memantine on both
      cognitive and depressive symptoms in Dep-MCI patients and will potentially have broader
      public health implications because Dep-MCI is a wide-spread clinical problem where management
      needs to be improved.
    

Intervention name(s): es-citalopram; Memantine
Intervention type(s): Drug; Drug
Intervention description(s): es-citalopram 10mg/day will be given for the first week, and 20mg/day starting at week 2.; After two weeks on Lexapro, Memantine 5mg will be added. The dose will increase to 10mg for the second week and will be increased at a rate of 5mg per week. Memantine dosage will not exceed 20mg.
Other intervention name(s): Lexapro; Namenda
Intervention MeSH terms: Memantine; Citalopram; Escitalopram
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Memory Decline; Depression; Elderly; Antidepressants; Treatment; memantine