Mortality and Poststroke Depression

To the Editor: In their innovative study on mortality and poststroke depression, Ricardo E. Jorge, M.D., et al. (1) found a significantly increased 9-year survival rate in stroke patients treated for 12 weeks with either fluoxetine or nortriptyline versus placebo, regardless of baseline level of depression, severity of stroke, concomitant medical illness, and impairment in cognitive and social functioning. The authors note that this remarkable extension of survival needs explanation.

One possibility might be the significant increase in levels of brain-derived neurotrophic factor found with long-term administration of antidepressants (2). Multiple investigators (see reference 3 for a review) have found that 1) levels of brain-derived neurotrophic factor are decreased in depression, 2) long-term use of antidepressants can prevent stress-induced reduction of brain-derived neurotrophic factor, and 3) stress can lead to atrophy and death of neurons, especially in the hippocampus (4). Indeed, antidepressant-induced neurogenesis in the hippocampus appears to be central to the behavioral effects of antidepressants (5). However, it is clear that brain-derived neurotrophic factor promotes neuronal survival, growth, and plasticity in the adult brain, whether or not depression is present.

Since stress and the accompanying increase in glucocorticoids seems to make neurons more vulnerable to ischemic insults (see reference 6 for an excellent review), the protective effect of increased levels of brain-derived neurotrophic factor in the brains of stroke subjects would be invaluable. It would have been interesting had the present authors measured baseline and subsequent levels of brain-derived neurotrophic factor in these patients since it seems plausible that survivors would have developed a significant and sustained increase in brain-derived neurotrophic factor compared with those who died.

Although the present study is intriguing, one hesitates to endorse the suggestion that all survivors of acute stroke be given antidepressants, especially in view of their association with falls and hip fractures (7) as well as bleeding with selective serotonin reuptake inhibitors (SSRIs) (8).