Critique date: Tue, 04/20/2010 - 1:56pm
Article Citation
Citation:
Ricardo, J et al. Escitalopram and Enhancement of Cognitive Recovery Following Stroke. Arch Gen Psychiatry. 2010; 67 (2): 187-196
Clinical Bottom Lines
Compared with patients receiving placebo or PST, patients receiving escitalopram showed higher scores in neuropsychological tests assessing global cognitive functioning, specifically measures probing verbal and visual memory.
The reported changes in neuropsychological performance resulted in an improvement in related ADLs.
Beneficial effect of escitalopram on cognitive recovery was independent of its effect on depressive symptoms and not influenced by stroke type or mechanism of ischemic stroke.
Escitalopram was well-tolerated and frequency of adverse effects was similar to that observed among patients receiving placebo.
Methods
Study Design:
Randomized, controlled clinical trial
Patient Population:
Patients recruited at University of Iowa Stroke Center between July 9, 2003, to October 1, 2007 were within 3 months of an index stroke. This was a subset of patients from a multicenter trial investigating the efficacy of escitalopram
Inclusions:
Age older than 50, younger than 90 years
Clinical and imaging findings consistent with cerebral hemisphere, brainstem, or cerebellar stroke
Patients with both ischemic and hemorrhagic strokes
Significant Exclusions:
Met DSM-IV diagnostic criteria for major or minor depressive disorder
Had 17-item Hamilton Scale for Depression (HAM-D) score greater than 11
Severe comprehension deficits (demonstrated by an inability to complete part 1 of Token Test) or with neuropsychological testing showing impaired decision-making capacity
Strokes secondary to complications from an intracranial aneurysm, AVM, or neoplastic process and stroke during course of MI or revascularization surgery
Life-threatening organ failure
Severely disabling musculoskeletal disorder
Cancer
Neurodegenerative disorders (idiopathic Parkinson or Alzheimer Diseases)
Met DSM-IV criteria for alcohol or substance abuse or dependence within the 12 months prior to enrollment
met DSM-IV criteria for depressive disorder at time to index stroke
Intervention/Exposure:
Neurologic and Neuroradiologic Evaluation
At entry, complete neurological evaluation performed
Lesion location classified: right/left hemispheres or brainstem/cerebellar
Stroke type: ischemic or hemorrhagic
Ischemic further categorized: large-artery atherosclerosis, cardioembolic, small-artery occlusion, undetermined or other cause
Severity of stroke
Neuroimaging scans
Randomization-129 patients randomized to either:
Escitalopram (10mg daily for pts<65 years, 5mg daily for pts≥65 years)
Placebo (all pills identical)
Problem Solving Therapy
Three main goals: 1) pt educated about relationship between depressive symptoms and problems in living and the attending rationale for learning adaptive problem-solving skills; 2) pt’s problems delineated through spontaneous report and questioning about key areas of living (e.g., finances, relationships, work problems); and 3) attempt is made to solve the problems in a structured way using the PST-PC intervention.
The intervention consists of seven stages: 1) defining and clarifying the problem, 2) establishing a realistic goal, 3) generating multiple alternative solutions, 4) implementing decision making guidelines, 5) choosing a solution, 6) implementing the solution, and 7) evaluating the outcome. Sessions last approximately 1 hour for the first visit and 30 minutes for each subsequent visit, for a total of four to six visits. An effort is made to implement the entire problem-solving intervention for at least one problem each session.
Assessment
Pts administered Structured Clinical Interview for DSM-IV at initial evaluation and at 3-,6-, 9-, and 12- month follow-ups
HAM-D, Hamilton Anxiety Rating Scale, and Functional Independence Measure (FIM) administered at initial and each follow-up interview
Socioeconomic status determined
Adverse effects recorded
Neuropsychological testing (Repeatable Battery for Assessment of Neuropsychological Status, Trail-Making Test, Controlled Oral Word Association, Wechsler Adult Intelligence Scale, Stroop Test)
Emphasis on memory and executive functioning
Performed at baseline and at end of intervention for 70-85 minutes by trained technician (masked to treatment status)
Outcome Measures:
Change in scores from baseline to the end of treatment for the RBANS and Trail-Making, Controlled Oral Word Association, Wechsler Adult Intelligence Scale-III Similarities, and Stroop Tests
Analysis:
Univariate analysis
Assessed whether treatment predicted change in neuropsychological scores between baseline and end of treatment evaluations after controlling for potential confounders
Age, education, change in HAM-D scores, time elapsed between index stroke and start of treatment, baseline FIM score and the stroke mechanism
Built several multiple linear regression models for each outcome of interest
Intent-to-treat analysis
Conclusion
Results:
129 patients randomized, 117 began treatment
Patients who received PST were older than patients randomized to escitalopram or placebo
Patients who received PST had HTN more often than those randomized to escitalopram
No differences between 3 groups in baseline scores of neuropsychological tests assessing memory and executive functioning
RBANS Total Score
Before controlling for other covariates, there was a difference in change in RBANS--Change in score higher among participants who received escitalopram compared with other 2 groups
After controlling for change in HAM-D and stroke mechanism--escitalopram group had higher change in score compared w/other 2 groups (E=9.9, PST=1.9, p<0.1, placebo=4, p=.02)
After combining placebo group and PST group into single group and then controlling for HAM-D and stroke mechanism (fig 2)--there was an effect of escitalopram on change in RBANS total score (10 vs 3.1, p<0.1)
RBANS Delayed Memory Score
Before controlling for covariates, a difference in change was noted between the 3 groups
Change in score higher among pts receiving escitalopram than in other 2 groups
After controlling for time elapsed between stroke and treatment, change in HAM-D score, stroke mechanism, and interaction between treatment and change in HAM-D
Group receiving escitalopram had greater change in score than the other 2 groups
After combining placebo and PST groups, there was a significant effect of escitalopram on change in RBANS delayed memory score (Fig 2) after controlling for time elapsed between stroke and treatment, change in HAM-D score and stroke mechanism
RBANS Immediate Memory Score
Before controlling for covariates, a difference in change was noted between the 3 groups
Change in score higher among pts receiving escitalopram than in other 2 groups
After controlling for time elapsed between stroke and treatment, change in HAM-D score, stroke mechanism and interaction between treatment and change in HAM-D:
Group receiving escitalopram had a higher change in score thatn other 2 groups
After combining placebo and PST groups, there was a significant effect of escitalopram on change in RBANS immediate memory score (Fig 2) after controlling for time elapsed between stroke and treatment, change in HAM-D score and stroke mechanism
No effect of treatment on change in RBANS attention, language or visuospatial/construction domains; Trail-making test, COWA, Stroop Trial or WAIS
FIM
Escitalopram group showed greater changes in FIM cognitive domain than those not receiving it
Escitalopram group showed greater changes in FIM memory scores than other 2 groups
There was a positive correlation between change in RBANS total scores and change in FIM total scores
Adverse Events/Effects
No differences between groups in frequency of any events
No differences between groups in frequency of hospital admissions due to GI Bleed or falls
Concerns Regarding Methodology, Applicability to Older Adults, etc.:
Limitations:
Study obtained neuropsychological data on nondepressed patients with mild to moderate strokes recruited in specialized stroke unit, may not apply to other stroke patients with different characteristics
Patients receiving escitalopram were younger than patients in other groups
Study did not obtain baseline neuroimaging variables and therefore examine effect on cognitive outcomes
Comments:
Escitalopram was hypothesized to have a beneficial effect on memory and executive function, but effect was only observed in immediate memory and delayed recall.
Present findings suggest that chronic administration of SSRIs may also improve cognitive function
Funding Source and Role:
Supported by Grant R01 MH-65134 from the National Institute of Mental Health. While multiple authors have had affiliations and/or support with various pharmaceutical companies and Forest Laboratories, none of the design, analysis, or expenses (including cost of medications) of this study were supported by monies, materials or any intellectual input from the companies or Forest Laboratories.
Created By:
Lorie N. Smith, MD, Fellow, Integrated Palliative Medicine and Geriatrics Brookdale Department of Geriatrics and Palliative Medicine Mount Sinai School of Medicine
This is a review of the validity of a single study; the ‘bottom lines’ do not reflect comparison with the rest of the literature on this subject.