Clinical Topics & News

Epilepsy and Comorbidities

Nikesh Ardeshna, MD/> Dr. Ardeshna is the Medical Director of Adult Epilepsy Services at Royal Oak Hospital, Beaumont Health System, in Royal Oak, Michigan.



The primary focuses of epilepsy treatment are seizure control and achieving seizure freedom. Nevertheless, certain additional comorbidities and associated medical conditions are seen more frequently in patients with epilepsy, compared with the general population, and these comorbidities require evaluation and treatment. These conditions are either directly or indirectly, and wholly or in part, due to the underlying seizures and epilepsy. Their exact causes are not known, but they may share common electrical and chemical mechanisms. Examples of these comorbidities include cognitive changes or deficits (including memory loss) and mood disorders. This summary discusses the basic characteristics of these comorbidities.

These comorbidities have garnered more attention over the last few years not only because patients are reporting these symptoms more frequently, but also because these symptoms, in addition to seizures, can significantly affect a patient’s quality of life. This influence, in turn, has led to more research and literature documenting these comorbid conditions. At times, the conditions’ impact on quality of life can be greater than the impact of the epilepsy itself.

Cognitive deficits (including memory loss) or mood changes can be present before the diagnosis of epilepsy. These deficits can be related to or independent of the epilepsy. Objective measurement of various cognitive domains is performed mainly through neuropsychologic testing.

Diagnosis and management of these associated medical conditions is integral to the comprehensive care of patients with epilepsy. Diagnosis is not easy, in part because some of these symptoms can be considered subjective. Patients are at times reluctant to discuss these issues and sometimes do not mention them unless the physician inquires about them. Many times it is another family member who brings up these concerns.

To complicate maters further, some of the conditions mentioned above can be side effects of antiepileptic drugs (AEDs), which are the first line of treatment for seizures. In addition, if a mood disorder, memory loss, or certain other medical condition is already present, it can affect the choice of AED treatment. Consequently, epilepsy management is often a delicate balancing act between controlling seizures and minimizing side effects while maintaining quality of life.

Cognition can be affected by AED dose, rate of titration, concentration, and number (as in polytherapy). Cognition can also be affected by the age of seizure onset, seizure type, duration, severity, and cause. Cognitive changes in patients with epilepsy include, but are not limited to, deficits in attention, processing, executive function, and memory. All of these deficits, either individually or in combination, can affect school or work performance. Consequently, patients may need accommodation. The physician should serve as the patient’s advocate and support, in appropriate cases, the need for accommodation.

The cognitive change that raises the most patient concern is memory loss. Recurrent seizures associated with temporal lobe epilepsy are correlated with hippocampal volume loss and memory impairment. Memory loss is more likely with longer epilepsy duration and uncontrolled epilepsy. Studies have shown that achieving and maintaining control of epilepsy as soon as possible minimizes memory loss. In appropriate candidates, temporal lobe epilepsy surgery may improve cognition by achieving seizure freedom and reducing the need for antiseizure medication. No medication is indicated for the treatment of memory loss associated with seizures.

Mood disorders are more common in patients with epilepsy, compared with the general population. The most common mood disorders in patients with epilepsy are depression and anxiety. Sometimes these disorders can coexist.

Approximately 30% of patients with epilepsy have depression. Treatment of depression in patients with epilepsy is highly recommended and has been shown to reduce seizures and improve quality of life.

There is also a bidirectional relationship between epilepsy and depression. Individuals with one condition are more likely to have the other, compared with someone who does not have either condition. The best treatments for depression in patients with epilepsy are selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy. Sometimes these treatments are used in combination. Tricyclic antidepressants are second-line therapies because of their greater risk for side effects.

In addition, depression is the primary risk factor for suicide. The rate of suicide in patients with epilepsy is approximately 25 times greater than that in the general population. According to an FDA warning in 2008, AEDs can increase the risk of suicidal behaviors and ideation. However, some epilepsy specialists do not fully agree with these findings because of how the data were collected. It is unclear whether this increased risk of suicidal behaviors and ideation results from the AED or the epilepsy itself.

Anxiety is also more frequent in patients with epilepsy; its prevalence is approximately 19%. Anxiety may result partly from the ongoing fear of having a breakthrough seizure and the stigma associated with epilepsy.

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