OBJECTIVES: An array of antidepressant agents are available in the treatment of geropsychiatric patients with depression. While most current agents, such as the selective serotonin reuptake inhibitors (SSRI’s) (e.g., fluoxetine; sertraline) and agents acting upon both serotonin and norepinephrine (e.g., mirtazapine; venlaxafine), are reasonably effective in ameliorating depressive symptomatology, less is known about the impact of these agents on other common areas of deficit in older depressed patients, such as cognition. This study examines change in cognitive functioning in geropsychiatric patients (age 55 and older) with major depression (ICD-9-CM codes 296.20-296.36) treated with fluoxetine (n=269), mirtazapine (n=275), sertraline (n=713), or venlaxafine (n=259). METHODS: Data were obtained from the CQI+SM Outcomes Measurement System, a Joint Commission of Accredited Hospital Organizations (JCAHO) ORYX accepted performance improvement system, which tracked patients admitted to geropsychiatric inpatient programs in 111 general hospitals across 33 states between 1997-1999. Cognitive functioning was measured at admission and discharge using the Mini-Mental State Examination (MMSE) (Folstein, Folstein, & McHugh, 1975). A Medication Usage Questionnaire was used to track medications prescribed to patients just prior to admission and at discharge. One-way Analyses of Variance and if significant, Tukey’s pairwise comparisons, were used to compare medication groups. RESULTS: At admission, patients exhibited moderate evidence of cognitive impairment (Mean MMSE score of 21 out of 30). Medication groups were indistinguishable on change scores in cognitive functioning from time of admission to discharge (average length of stay around 16 days). The average change score on the MMSE was 1.1 to 1.6 points, suggesting very mild improvement. CONCLUSIONS: Antidepressant agents in this analysis were associated with modest improvement in cognitive functioning as assessed by the MMSE. New treatment modalities that improve cognition along with depressive symptomatology in older patients would be beneficial.