Fluoxetine, Learning and Memory in Epilepsy

FLAME is a randomised controlled, double blind feasibility trial investigating the efficacy of fluoxetine treatment in improving memory and learning impairments in patients with mesial temporal lobe epilepsy.

Learning problems and memory problems are common in people with mesial temporal lobe epilepsy (TLE). There are currently no treatments available to combat these problems and it represents a significant unmet clinical need.

Part of the reason that there are no effective treatments is because we do not really understand what goes wrong in the brains of people with TLE which means they develop learning and memory problems. We know that new nerve cells are continually being formed (neurogenesis) in a part of the brain called the hippocampus throughout adult life. The hippocampus is very important for learning and memory and we know that the new-born nerve cells are an important part of this. We also know that neurogenesis is permanently reduced in chronic TLE, which may explain some of the learning and memory problems from which patients suffer.

Studies have shown that the widely available oral antidepressant drug fluoxetine, restores both the production of new nerve cells. It can also restore the ability to learn a difficult spatial navigation task in an animal model of temporal lobe epilepsy that exhibits exactly the same pattern of learning and memory problems seen in patients with chronic TLE.

The Fluoxetine, Learning and Memory in Epilepsy (FLAME) study will examine whether oral fluoxetine has a similar effect in patients with chronic TLE who are not actively depressed. If successful it will provide proof of concept that drug treatment can restore learning ability in patients with TLE, using currently licensed drugs.