“That's Great if You're a Rat”

"That’s great if you’re a rat," you say, when you find out that an article published last month (Science 319, 385 (2008)) showed that in the brain of the adult rat, Prozac (fluoxetine) restores plasticity, or changeability – the potential to adapt after injury. But there's more to the story. This finding shows us a possible reason why antidepressants, given for a few months soon after strokes in humans, improve survival and recovery years after the treatments are finished.

Plasticity is a sort of brain rewiring

Plasticity, the ability of the brain to change, adapt, and form new connections, is usually seen only in the immature, developing brain. In the Science journal article, antidepressants induced plasticity, or changeability, which allowed recovery from an experimentally induced brain injury in the rat. Without the drug, recovery did not occur.

Benefits of antidepressants after stroke – improved function

In humans, remarkable benefits have been seen when antidepressants are given after strokes. In a clinical trial (J. of Nerv. & Mental Dis. 191, 645 (2003)), patients in one group were given a 3 month course of antidepressants within a month after a stroke. Patients in the other group were given the same treatment, but the antidepressants were started after more than one month post-stroke, an average of 140 days after the stroke. The early treatment group had a better recovery with respect to self care, mobility, speech, less cognitive impairment, and in other ways. The improved recovery in the early treatment group was maintained for over 2 years.

Another benefit – better survival

In another study (Am. J. Psych. 160, 1823 (2003)), three months of antidepressants after a stroke dramatically reduced death rates for as long as 9 years. Antidepressants or an inert placebo were given to patients within 6 months after a stroke. At the 9 year follow up, 68% of the antidepressant group survived compared to 36% of the placebo patients. This benefit occurred whether patients were depressed or not when they entered the study.

How do the antidepressants cause these effects?

The mechanisms by which antidepressants produce these benefits in stroke patients are unknown. Antidepressants given soon after a stroke may, as in rats, enhance the ability of the brain to recover and adapt. Antidepressants are known to increase the levels of brain growth factors which may enhance the growth and survival of brain cells.

Should antidepressants after stroke be a standard treatment?

Obviously, more research is needed. One could make the case that soon after a stroke, all patients should be put on antidepressants whether or not they are depressed. One class of antidepressants, the selective serotonin uptake inhibitors (SSRIs), can increase the risk of falls, hip fractures, and bleeding. However, the treated patients still had overall improvements in survival and function. So the benefits appear to outweigh the risks.

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