Thursday, April 22, 2010

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


The Shrink said...

What's the pathology in a stroke?

Isn't it something to do with ischaemic damage and subsequent neuronal cell death/gliosis?

So stroke damage to the temporal lobe/parietal lobe will effect recognition/working/declarative memory. I'm fine with that.

Where I struggle is how, when a stroke's caused structural brain damage, fiddling with serotonin levels is going to make it all better?

If the disorder's that you've a structural problem, having organic brain damage, how's a functional (chemical) pharmacological solution going to help?

I know, I know, it's awfully reductionist and we know cognitive stimulation therapy etc has evidenced restorative function, but that's a physiological developmental change, enhancing cognitive performance, not a solution/fix/feigned restoration of function that escitalopram's purported to effect.

Anonymous said...

A few years ago I sat next to a doctor on a plane who told me that he'd suffered severe brain damage after an auto accident, and that it was only reversed after several weeks of IV prozac. I believe his argument contra "it would have fixed itself" was that months had passed and his recovery had already plateaued.
Probably the sort of anecdote that motivated this study.

NeuroPsych said...

"IV Prozac." As in intravenous? I've only seen one study with IV Prozac and it was done 1998 on rats. I don't think that stuff is commercially available nor FDA approved.

Anyone have more info?

Anonymous said...

Most likely the rationale for this study was the neurotrophin theory of antidepressant drug action. After a lag period, antidepressant drugs and also ECT induce the synthesis of BDNF – brain derived neurotrophic factor. BDNF, in turn, is supposed to help in the process of neurogenesis, at least in the hippocampus. Lately, BDNF has become the new serotonin, and the inspiration for many new and trite just so stories.

Barney Carroll.

Anonymous said...

Hey: What's your take on this article and new book about the alleged epidemic of psychiatric drugs?

Neuroskeptic said...

But here's an observational study finding that patients on SSRIs when they have a stroke do worse... although that might just be because they were depressed which is why they were on SSRIs.

Anonymous said...

what do you make of this study?
Lancet Neurology
Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial
"In patients with ischaemic stroke and moderate to severe motor deficit, the early prescription of fluoxetine with physiotherapy enhanced motor recovery after 3 months. Modulation of spontaneous brain plasticity by drugs is a promising pathway for treatment of patients with ischaemic stroke and moderate to severe motor deficit."

Maria said...

Depression occurs in up to two-thirds of patients with stroke, and placebo-controlled trials have shown improvement in post-stroke depressive symptoms with antidepressant drug treatment. However, recent studies suggest that antidepressants could also improve outcome from stroke itself. At least three mechanisms may be involved: protection against acute ischemic neuronal injury, increased ischemia-induced neurogenesis and enhanced brain repair.cardiologo cirujano general y plástico dermatologo endocrinologo gastroenterologo ginecologo homeopata médico internista nefrologo neumologo neurologo oftalmologo ortopedista otorrinolaringologo pediatra urologo consulta medica online consultar medico online medico online doctor online psicologo online psiquiatra online chatear psicologo online preguntar con psicologo online consulta psicologia online consultar psicologo online abogado colombia online abogado online consultar abogado online abogado españa online consultas abogado mexico online dentista online veterinario online consulta online consultar Thanks