Memantine Plus Es-citalopram in Elderly Depressed Patients With Cognitive Impairment

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.