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Response to Antidepressant Medications in Late-Life Depression Across the Spectrum of Cognitive Functioning

Aaron M. Koenig, MD; Meryl A. Butters, PhD; Amy Begley, MA; Semhar Ogbagaber, MS; Abdus S. Wahed, PhD; and Charles F. Reynolds III, MD

Published: February 15, 2014

Article Abstract

Objective: Late-life depression frequently co-occurs with cognitive impairment. To inform clinical management of these conditions, we examined the hypotheses that, relative to cognitively normal elders meeting DSM-IV criteria for major depressive disorder, those with cognitive impairment would require greater intensity of pharmacotherapy to reach criteria for antidepressant response and would take longer to respond.

Method: Using data from the MTLD-3 study, we conducted a series of secondary analyses examining the implications of cognitive impairment for short-term, open-trial pharmacotherapy of late-life depression (major depressive disorder in individuals 65 years and older). The treatment algorithm consisted of 3 steps: initial treatment with a selective serotonin reuptake inhibitor (SSRI), a switch to a serotonin-norepinephrine reuptake inhibitor (SNRI) if the patient did not respond, and addition of an atypical antipsychotic if the patient did not respond to the SNRI. The first subject entered the protocol in April 2004, and the last subject exited in September 2009. We examined data for participants who completed the acute phase of MTLD-3 as responders and received a cognitive diagnosis (N = 153) based on National Alzheimer’s Coordinating Center (NACC) Uniform Data Set criteria. We divided participants into 3 groups on the basis of NACC cognitive diagnosis: no cognitive disorder (n = 74), mild cognitive impairment (n = 60), and dementia (n = 19). For each group, we calculated the proportion of participants requiring first- (SSRI), second- (SNRI), or third-step (add-on atypical antipsychotic) treatment to meet criteria for response (17-Item Hamilton Depression Rating Scale score ≤ 10 for 3 consecutive weeks). We compared time to response across groups and correlates of nonresponse.

Results: The 3 groups did not differ in intensity of pharmacotherapy (P = .68) or time to response (P = .84). Nonresponse was more strongly correlated with longer major depressive episode duration (P = .0015), presence of recurrent depression (P = .002), and younger current age (P = .047), rather than cognitive status (P = .61).

Conclusions: Cognitive status does not appear to impact short-term pharmacotherapy response variability in individuals whose depression responds to treatment with open-trial antidepressants delivered in a supportive, university-based medication clinic.

J Clin Psychiatry 2014;75(2):e100-e107

Submitted: February 26, 2013; accepted September 19, 2013 (doi:10.4088/JCP.13m08442).

Corresponding author: Meryl A. Butters, PhD, Western Psychiatric Institute and Clinic, 3811 O’ Hara St, Room 462, Pittsburgh, PA 15213 (

Volume: 75

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