Do Antidepressants Enhance Stroke Recovery?

A few months ago, in the February issue of Archives of General Psychiatry appeared this study (1) title, "Escitalopram and Enhancement of Cognitive Recovery Following Stroke."

The design was simple: a placebo group, an escitalopram group, and a problem solving therapy group (a manual based therapy to treat depression in the medically ill). No patients in this group met diagnostic criteria for Major Depression (so why the PST group?) according to the Hamilton Scale for Depression (HAM-D). Patients were administered the following neuropsychological tests at baseline and post-treatment:

"-The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). This 25- to 30-minute battery assesses functioning in 5 domains (immediate memory, visuospatial/constructional, language, attention, and delayed memory). These domains are evaluated by 12 individual subtests, including List Learning, List Recall, List Recognition, Story Memory, Story Recall, Figure Copy, Figure Recall, Line Orientation, Picture Naming, Semantic Fluency, Digit Span, and Coding. This battery provides age-corrected norms for overall performance (total scale score) and scores in each domain."

(Number of Subjects in Each Treatment Group)

Here is what the researchers discovered: "We found a difference among the 3 treatment groups in change in RBANS total score (P<.01) and RBANS delayed memory score (P<.01)." They also found a significant result for immediate memory too, but for reasons beyond my knowledge (crack-cocaine?) they neglected to report this result. Test scores are below.

(Click to Enlarge)

The authors then engaged in a trite discussion about how escitalopram led to an improvement in memory and how serotonin theoretically affects memory, and blah, blah, blah.

On the surface, it does appear that escitalopram led to better outcomes: For the Total Score (a global measure of cognition) the escitalopram improved by 9.1 points compared to 5.7 for placebo; for delayed memory the escitalopram group improved by 12.4 points versus 5.9 for placebo, and for immediate memory (i.e., learning) the escitalopram group improved by 11.7 points versus 7.4 versus placebo.

However, look at the post-treatment final scores for both groups: total score: 89.8 (escitalopram) versus 91 (placebo); delayed memory 96.6 (escitalopram) versus 94.2 (placebo); and immediate memory 95.1 (escitalopram) versus 98.5 (placebo). Essentially, both groups post-treatment performance was nearly identical. The reason why the escitalopram group showed a larger magnitude in change was because that group had lower baseline scores.

The authors did point out that there was not statistical different between any of the baseline scores; however, that's irrelevant. Neuropsychological test performance scores are classified as either average, low average, mild deficit, moderate deficit, or severe deficit. Many of the escitalopram group baseline scores where in the mild-deficit range while the placebo group scores were in the low-average range. Functionally, that kind of difference is significant*.

Another factor not discussed is the rate of recovery in stroke patients. There is a pretty well delineated recovery curve for patients with mild-to-moderate strokes. Most recovery occurs in the first 6 months, followed by a slower recovery over the next 1-2 years. Those with more severe deficits will show greater initial recovery and then plateau at a level similar to the less sever group. This is why the groups matched on post-treatment assessment scores.

*It's actually more complicated than that. Scores actually fall within a certain range. So a person could perform in the mild-deficit range at point then in the low-average range at another point. So it's quite possible that these results reflect the error in the psychological instrument rather than a benefit from escitalopram.

Either way, I'm skeptical that escitalopram actually helped these people.



Jorge RE, Acion L, Moser D, Adams HP Jr, & Robinson RG (2010). Escitalopram and enhancement of cognitive recovery following stroke. Archives of general psychiatry, 67 (2), 187-96 PMID: 20124118