We know that there is an increased risk of depression among people with epilepsy, and conversely, that people who suffer from depression have an increased risk of epilepsy. Up until now, however, there has been a lack of knowledge about the extent of the increased risks and the temporal correlations between the diagnoses of the two brain diseases.

For this reason, researchers at Aarhus University Hospital and Aarhus University, in collaboration with colleagues at the University of Copenhagen, have conducted a major nationwide register-based study of the scope of and long-term correlation between epilepsy and depression. In addition, they have compared the risk of developing epilepsy and depression, respectively, with asthma, another chronic disease.

In the National Patient Register and the Psychiatric Central Research Register, the researchers identified 139,014 people with epilepsy, 219,990 people with depression, and 358,821 people with asthma, who received their first diagnosis in the period 1980 to 2016. The groups were comparable in terms of age and gender, and were adjusted for other diseases, drug abuse and the date of first diagnosis. In addition, comparable healthy control subjects were selected for each group.

Risk almost twice as high

The risk of developing depression turned out to be almost twice as high among people with epilepsy, compared to the control group of people without depression. The risk was greatest in the first months and years after the epilepsy diagnosis, but remained elevated throughout the observation period.

The frequency of epilepsy was more than double in people with depression, compared with the control group of people with no epilepsy, and just as in the reverse case, the risk was greatest in the first months and years after the depression diagnosis, but decreased over time. The frequency of epilepsy was highest among the youngest persons, i.e. those who were diagnosed with depression before the age of 20.

The frequency of depression and epilepsy in people with asthma was 1.63 times and 1.48 times greater, respectively, compared with the control group without asthma – i.e. the risk associated with asthma was lower than the risk associated with depression and epilepsy.

Need for further research

We know very little about the causes of the correlation between epilepsy and depression, but the results confirm that there is a correlation “both ways” between them, and because of the many test subjects involved and the long follow-up period in the study, it produced some very precise figures for the risk.

“The results underline the need for healthcare professionals to be aware of this correlation, and confirms that there is a need for further research to better understand the correlation between depression and epilepsy and the consequences of this relationship,” says Jakob Christensen, a consultant at Aarhus University Hospital and Associate Professor at Aarhus University.

“The discovery of the two-way correlation between depression and epilepsy supports previously presented theories that there may be common denominators among the pathogenic mechanisms that lead to epilepsy and depression, respectively.

There has been a concern that antidepressant medicine could trigger epileptic seizures, which may be the reason why some doctors have been reluctant to prescribe antidepressants to treat depression in patients with epilepsy.

“There are now many studies showing that antidepressant medicine in recommended doses, especially the commonly used SSRIs, are safe for patients with epilepsy,” says Jakob Christensen.

Behind the research results:

Type of study: Nationwide, register-based, matched cohort study.

Partners: Department of Neurology, Aarhus University Hospital, Department of Clinical Medicine and the National Centre for Register-based Research, Aarhus University, Department of Clinical Medicine and Department of Public Health, University of Copenhagen.

External funding: The study was financed by the Lundbeck Foundation, the Danish Epilepsy Association and the Novo Nordisk Foundation (NNF16OC0019126).

Conflicts of interest: None.

Read the scientific article: Eva Bølling-Ladegaard, Julie Werenberg Dreier, Lars Vedel Kessing, Esben Budtz-Jørgensen, Kasper Lolk, Jakob Christensen: Directionality of the Association Between Epilepsy and Depression: A Nationwide, Register-Based Cohort Study. Neurology. November 2022 DOI: 10.1212/WNL.0000000000201542

Further information

Eva Bølling-Ladegaard
Doctor of Medicine, Department of Neurology, Aarhus University Hospital and PhD student at the Department of Clinical Medicine, Aarhus University

Tel. + 45 2168 6302

E-mail EVBOEL@rm.dk

Jakob Christensen
Consultant, Department of Neurology, Aarhus University Hospital abd associate Professor at the Department of Clinical Medicine, Aarhus University

Tel. + 45 6086 5899

E-mail: jakob@clin.au.dk