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.


METHODS
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.
Horsfield
Stefanie A
SA
Mental Health Service Line, Department of Veterans Affairs Medical Center, Washington, DC 20422, USA.
Rosse
Richard B
RB
Tomasino
Vincent
V
Schwartz
Barbara L
BL
Mastropaolo
John
J
Deutsch
Stephen I
SI
D000368:Aged; D001930:Brain Injuries / Q000150:complications*; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014145:Trail Making Test
D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors