About 1 out of 3 people with epilepsy are at risk for a mood disorder such as depression, while this number may rise to 1 out of 2 people with poorly controlled seizures. These conditions (known as “comorbidities”) may be even more debilitating and worrisome than the seizures themselves.

People with epilepsy and depression are often prescribed antidepressants. However, little is known about how antidepressants affect the process of epileptogenesis (or how the brain develops epilepsy) and the long-term effects of antidepressants in someone with epilepsy.

What causes epilepsy and depression to occur together?

One reason is the understandable stresses of living with epilepsy. However, it’s also been suggested that depression may contribute to epilepsy. Also, changes within the brain that can occur from brain injury or genetic factors may cause both depression and epilepsy. For example:

Neurotransmitters (substances in the brain that help send messages among brain cells) like serotonin and its receptors may contribute to seizures and depression.

Part of the brain that regulates the release of hormones and other substances (the hypothalamus and pituitary gland) also involves areas of the brain that affect mood, stress, and behavior.

The presence of newborn cells in the brain could also explain the co-occurrence of epilepsy and depression.

Does medicine used to treat depression affect seizures?

A recent review describes what is known about when the two conditions (epilepsy and depression) happen together and how antidepressants may affect the brain of someone with epilepsy. The effects of antidepressants on epilepsy may be short-term or long-term. Some important findings:

First-generation antidepressants (also known as tricylic antidepressants) could trigger seizures, which made clinicians a bit reluctant to prescribe these to people with epilepsy.

Recent studies suggest that newer, second-generation antidepressants may be helpful in epilepsy by decreasing seizure frequency.

There is much evidence that suggests that the use of antidepressants in epilepsy is beneficial, but the authors stress the need for caution.

Until now, studies have only looked at the effects of antidepressants on seizures, but not on the mechanisms that cause seizures in the first place. This type of study would be difficult to do in people with epilepsy, but could be done with animal models.

How can research in animals help us understand depression and seizures in people?

There are many animal models of epilepsy that scientists use in the lab. Some, like the maximal electroshock (MES) model can help study the new development of seizures in a rodent that is otherwise healthy. Chronic models of epilepsy take a longer time but help researchers study the circuits that underlie epilepsy in the brain.

The effects of antidepressants on epilepsy should be studied in chronic animal models of epilepsy to give us a better understanding about the long-term effects of antidepressants in an epileptic brain.

Although antidepressants have positive effects in epilepsy, more studies should be done in animal models to understand how this works.

Important Tips for People with Epilepsy