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

Abstract

Objective Depression in later life frequently coexists with cognitive impairment. To inform clinical management of these co-occurring conditions, we examined the hypotheses that, relative to cognitively normal elders meeting DSM-IV criteria for major depression, those with cognitive impairment would require greater intensity of pharmacotherapy to reach criteria for response, and take longer to respond. Method Using data from the recent Maintenance Therapies in Late Life Depression (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 depression in individuals aged 65 years and older). This short-term treatment trial consisted of three steps: initial treatment with an SSRI, subsequent switch to an SNRI if patient did not meet criteria for response, and addition of an atypical antipsychotic (AAP) for non-response to SNRI monotherapy. The first subject entered the MTLD-3 protocol in April 2004, and the last subject exited the protocol in September 2009. We examined data for participants who completed the acute phase of MTLD-3 as responders and received a consensus cognitive diagnosis (N=153) from the University of Pittsburgh Alzheimer’s Disease Research Center, based on National Alzheimer Coordinating Center Uniformed Data Set criteria. We divided participants into three groups, based on cognitive diagnosis: normal cognitive function (N=74), Mild Cognitive Impairment (N=60), and dementia (N=19). For each group, we calculated the proportion of participants who required first (SSRI), second (SNRI), or third-step (add-on AAP) treatment to meet criteria for clinical response (HRSD-17 score ≤ 10 for three consecutive weeks). We compared time to response across groups, and examined patterns of response by inspection of weekly HRSD-17 scores. Finally, we examined correlates of non-response. Results The three groups did not differ significantly with respect to time to response (p=0.84), trajectories to response, or intensity of antidepressant pharmacotherapy (p=0.68). Non-response was more strongly correlated with longer index MDE duration (p=0.0015), presence of recurrent depression (p=0.002), and younger current age (p=0.047), rather than with cognitive status (p=0.61). Conclusion Cognitive status does not appear to impact short-term pharmacotherapy response variability in individuals whose depression responds to treatment with open-trial antidepressant pharmacotherapy delivered in a supportive, university-based medication clinic.

Disrupted Interhemispheric Synchrony in Default Mode Network Underlying the Impairment of Cognitive Flexibility in Late-Onset Depression

“…Furthermore, impaired visuospatial ability, information-processing speed, and delayed memory were persistent despite the remission of depressive symptoms after 1 year (Bhalla et al, 2006 ). Emerging research proposed that late-life depression (Koenig et al, 2014 ), especially late-onset depression (LOD), exhibit more dementia-related neuropathology, which could be regarded as an important risk factor for deterioration in Alzheimer’s disease (Sierksma et al, 2010 ; Dillon et al, 2014 ; Sachs-Ericsson et al, 2014 ). The problem with the medication of LOD is the lack of specific, objective biomarkers to assist clinicians in establishing an individualized diagnosis and in improving specific treatment.…”

Persistent benefits of slow titration of paroxetine in a six‐month follow‐up

“…Cognitive functioning was not assessed in our patients. Before discussing this as a limitation, recent studies have reported no substantial impact of cognitive status on short‐term antidepressant response variability in individuals 65 years and older (Koenig et al ., ); moreover, cognitive‐impaired subjects are not considered for treatment in our center. Relapses and recurrences could not be estimated in our sample because of the small number of complete follow‐ups.…”

Depression in the Context of Medical Disorders: New Pharmacological Pathways Revisited

“…treatment with sertraline in patients with Alzheimers Disease is not associated with greater improvement in cognition at week 24 than treatment with placebo [128]. Cognitive status does not appear to be impacted by short-term pharmacotherapy, at least in patients treated with SSRI and SNRI [129]. Given this potential risk and the myriad of other well-known adverse effects (i.e.…”