Fluoxetine's effects on cognitive performance in patients with traumatic brain injury

Objective: There are preclinical data showing that fluoxetine stimulated expression of Brain Derived Neurotrophic Factor (BDNF) and its specific tyrosine kinase receptor, and caused neuritic elongation and increased dendritic branching density of CA3 hippocampal pyramidal cell neurons in rodents. The latter effect of fluoxetine has been referred to as neuronal remodeling. In view of this preclinical data, we wondered if specific cognitive measures could serve as novel therapeutic targets for fluoxetine in head-injured patients. Theoretically, fluoxetine-induced "neuronal remodeling" might improve cognition, independently of a primary effect on mood. Method: In an open-label pilot investigation, fluoxetine hydrochloride (Prozac; 20-60 mg/day) was administered to a heterogeneous group of five head-injured patients with either no or moderate depression for a period of eight months. These patients had no histories of prior treatment with antidepressant medications. They were administered cognitive and memory tests at baseline and after eight months of treatment on fluoxetine. Results: The preliminary results showed that fluoxetine improved mood, in addition to improving performance on the Trail Making Test Part A, an attentional-motor speed task, and the letter-number sequencing subtest of the WAIS-III, a measure reflecting "working memory." Conclusions: Although fluoxetine had beneficial effects on some measures of cognition, more work is needed to connect these improvements with neuronal remodeling.