Objective Selective Serotonin Reuptake Inhibitors (SSRIs) are the most commonly prescribed medications for geriatric depression. The association of late-life depression and cognitive impairment has been well documented. However, there have been few placebo-controlled trials examining the impact of SSRIs on cognitive functioning. Design Pre-post neuropsychological data collected as part of an 8-week, double-blind, placebo-controlled trial of citalopram in depressed patients aged 75 years and older were used to examine change in cognitive functioning. Setting University affiliated outpatient psychiatry clinics. Participants One hundred seventy-four community dwelling men and women 75 years or older with non-psychotic unipolar depression. Measurements Neuropsychological assessments included mental status (Mini-Mental Status Exam), psychomotor speed (WAIS-III Digit Symbol Subtest), reaction time (Choice Reaction Time), visual-spatial skill (Judgment of Line Orientation), executive functioning (Stroop Color/Word Test), and memory (Buschke Selective Reminding Test). Results Differences in the pattern of change by treatment group depended on responder status. Citalopram non-responders were the only group to decline on verbal learning and psychomotor speed. Citalopram responders showed significant improvement in visuospatial functioning compared to non-responders in either condition, but their improvement was not greater than responders on placebo. Citalopram responders showed greater improvement on psychomotor speed than citalopram non-responders, but their improvement was not greater than placebo responders or non-responders. Conclusions Medication may have a deleterious effect on some aspects of cognition among patients age 75 and over who have not responded. This suggests that patients should not be maintained on a medication if they have not had an adequate response.

Objectives To determine whether there is differential response to placebo or citalopram among older patients with and without deficient response inhibition. Design 8-week, double-blind, placebo controlled trial. Setting Outpatient psychiatry. Participants Unipolar depressed patients aged 75 years and older. Intervention citalopram (20–40 mg/d) or placebo pill. Measurements Baseline Stroop Color Word Test and weekly 24-item Hamilton Rating Scale for Depression assessments. Results Citalopram treated patients with deficient response inhibition did significantly worse than placebo treated patients with deficient response inhibition. Conversely, citalopram treated patients without deficient response inhibition did significantly better than placebo treated patients without deficient response inhibition. Conclusion Patients with late-life depression and deficient response inhibition respond worse to SSRI than placebo. These findings suggest that there may be a deleterious interaction between deficient response inhibition and antidepressant medication in late-life depression and that the mechanism of SSRI and placebo response is different.