Writer: Poppy Pendergast
Editor: Celine Tedja
Artist: Jin Yu
Epilepsy is one of the oldest recognised medical conditions in the world, with accounts of what we now believe to be epileptic seizures dating back to 2000 BCE. Epilepsy is defined as a brain disorder characterised by recurring, unprovoked seizures. For most of this time, the association between epilepsy and depression has been recognised and commented on, for example by Hippocrates, who stated, “Melancholics ordinarily become epileptics, and epileptics melancholics.”
The evidence for this link has also been well documented in more recent times, with research showing that adults with epilepsy are twice as likely to experience feelings of depression compared to adults without epilepsy. The data also shows a correlation between severe epilepsy and severe depression; however, questions regarding the mechanism responsible for this relationship remain unanswered.
It has been hypothesised that the difficulties associated with living with epilepsy lead to depression. It seems logical that the unpredictable nature of seizures and their impact on quality of life and independence would lead to poorer mental health. Other common comorbidities and potential complications, such as sudden unexpected death in epilepsy (SUDEP), can cause excess stress and worry, therefore negatively impacting wellbeing. Epilepsy can also be a barrier to educational opportunities and certain occupations, potentially leading to financial issues, which have been shown to contribute significantly to poor mental health. This is likely particularly significant for those living in low- and middle-income countries, which account for nearly 80% of people living with epilepsy. Perhaps most importantly, discrimination and misunderstanding have surrounded epilepsy for centuries, and so it seems probable that the widespread stigma and fears of disclosure that often come with a diagnosis could contribute to feelings of depression.
It has also been argued that seizure medications may contribute to changes in mood. While some may have positive effects on mood, there is evidence that others could worsen mood, particularly at high doses. Therefore, in 2008, the FDA warned that antiepileptic drugs may increase the risk of suicide or suicidal thoughts through a range of possible mechanisms, such as potentiation of GABA neurotransmission and by causing folate deficiency. However, a 2009 review found that many other factors were not addressed when analysing the association, including the risk of pre-existing depression in people with epilepsy, potentially invalidating the research and suggesting that antiepileptic medications may not be causing depression in epilepsy patients.
In addition, it must be considered that the relationship between epilepsy and depression appears to be bidirectional, since people with depression also have a higher risk of developing epilepsy. One potential explanation for this could be the proconvulsant properties of some types of common antidepressants, as these drugs lower the seizure threshold of the brain. However, the two-way interaction has also been demonstrated in those with depression not treated with medication. This points towards the conclusion that there is something about the physiology of the brain that makes a person with epilepsy more likely to experience depression, and vice versa. It is suggested that some of the areas of the brain responsible for certain types of seizures also affect mood, and therefore, physiological abnormalities in these areas could lead to both epilepsy and depression. Further evidence for this hypothesis is based on the fact that people with epilepsy have a higher risk of developing depression and other mood disorders before even experiencing their first seizure. This would suggest that some of the changes in the brain that make a person susceptible to seizures (such as lower neural plasticity or brain damage due to traumatic brain injury or infection) could also make them more susceptible to depression than the general population.
Nevertheless, most experts in the field would agree that regardless of the nature of the relationship between epilepsy and depression, care for patients living with these conditions must be better integrated, given that they often occur together. Progress in this area has the potential to improve many people’s lives, given that around 50 million people have epilepsy globally, and a large proportion of these also experience depression. If the two conditions are linked by a common physiological cause, then it is clearly relevant to consider how they could both be treated using a similar method, and how this treatment may differ from practices used to treat just one of the conditions in isolation. Even if they do not share the same root cause, their complex interplay necessitates an understanding of both conditions, which is not always the case. This is demonstrated by the fact that most of the information regarding treating depression in patients with epilepsy is anecdotal, rather than being based on randomised controlled trials or any kind of systematic investigation.
It is critical that we take the mental health comorbidities of epilepsy more seriously, as they can affect self-management and prognosis, even when symptoms are mild. Therefore, more holistic treatment could significantly improve patient experiences. These comorbidities are also associated with increased inpatient care and hospitalisations, so improving treatment methods would also be economically beneficial.
Most research suggests that a multidisciplinary team approach is necessary to tackle the difficulties patients face when dealing with the interaction between epilepsy and depression. This should include the integration of mental health professionals into epilepsy care teams, as well as mental health training for neurologists, many of whom have identified this as a key part in improving care. Through a better understanding of the intersection between these two challenging conditions, patients can be better supported in maintaining both their physical and mental health, ultimately minimising or eliminating the negative impact that these conditions might have on their quality of life.
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