SSRI escitalopram improves cognitive function recovery in recent stroke survivors

A randomized controlled trial of recent stroke survivors found that patients receiving the selective serotonin reuptake inhibitor escitalopram had greater improvement in global cognitive function than those receiving placebo or Problem Solving Therapy.

Key Points

A randomized controlled trial of recent stroke survivors found that patients receiving the selective serotonin reuptake inhibitor (SSRI) escitalopram had greater improvement in global cognitive function than those receiving placebo or Problem Solving Therapy (PST). Escitalopram improved both verbal and visual memory function, according to the report published in the February 2010 issue of the Archives of General Psychiatry. This beneficial effect of escitalopram on post-stroke cognitive function appeared to be unrelated to the drug's well-documented antidepressant effects.

There has been growing interest in identifying therapies that can be given during the first few months post-stroke, the period when the greatest degree of spontaneous recovery of initial cognitive function is seen. The researchers stressed in the article, "A therapeutic intervention that fosters cognitive recovery of stroke patients has the potential to significantly reduce the burden of this disease."

STROKE STATISTICS

In order to examine the effect of escitalopram on post-stroke cognitive function, researchers evaluated 129 patients enrolled in a previous randomized controlled trial. These patients were randomly assigned within 3 months of their ischemic or hemorrhagic stroke to receive escitalopram 5 or 10 mg (n=43) or placebo (n=45) in a double-blinded fashion, or to open-label PST without medication (n=41).

Key study end points included the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a 25- to 30-minute group of tests that assesses cognitive functioning in 5 domains (immediate memory, visuospatial/constructional, language, attention, and delayed memory). Other neuropsychological tests administered included the Trail-Making test, Controlled Oral Word Association, Wechsler Adult Intelligence Scale III-Similarities, and Stroop tests.

After 12 months of participant follow-up, researchers found the RBANS immediate memory score was improved to a greater extent in the escitalopram arm (adjusted mean change from baseline: 13.4) than in the PST arm (adjusted mean change from baseline: 2.0), placebo arm (adjusted mean change from baseline: 7.2), and the 2 non-escitalopram arms combined (adjusted mean change from baseline: 5.3) (P<.04 for all) after adjusting for potential confounders including the drug's effect on depression (assessed using the Hamilton Scale for Depression).

Similar results were seen on the RBANS delayed memory score, with patients in the escitalopram-treated arm of the trial (adjusted mean change from baseline: 11.2) showing greater improvement than those in the PST (adjusted mean change from baseline: –0.7), placebo (adjusted mean change from baseline: 3.9), and combined non-escitalopram arms (adjusted mean change from baseline: 2.5) (P<.02 for all). Likely as a result of benefits in immediate and delayed memory, researchers also detected a significantly better effect of escitalopram on the RBANS total score (adjusted mean change from baseline: 9.9) compared with the PST arm (adjusted mean change from baseline: 1.9), placebo arm (adjusted mean change: 4.0), and the 2 non-escitalopram arms combined (adjusted mean change from baseline 3.1) (P<.02 for all). The effect of escitalopram on other neuropsychological measures was no better than non-escitalopram treatment arms.

RESTORATIVE AGENTS

"Overall, the neurotrophic effects of antidepressants and the fact that they are widely used medications of proven safety make them excellent candidates for use as restorative agents in the subacute phase of stroke and other forms of brain damage," remarked Ricardo E. Jorge, MD, the lead trial researcher and associate professor of psychiatry at the University of Iowa. "The utility of antidepressants in the process of post-stroke recovery should be further investigated," Dr Jorge said.

The National Institute of Mental Health was the sole financial supporter of this trial.

SOURCE

Jorge RE, Acion L, Moser D, Adams Jr HP, Robinson RG. Escitalopram and enhancement of cognitive recovery following stroke. Arch Gen Psychiatry. 2010;67:187–196.

Lloyd-Jones D, Adams R, Carnethon M, et al.; for the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics - 2009 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009;119:480–486.