Epilepsy and Depression

By Dominique Celestino

Epilepsy is defined as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures (Fisher et al., 2014). In this paper, a seizure refers to a sudden burst of electrical activity within the brain impairing an individual for up to 3 minutes or more. A diagnosis of epilepsy is dependent upon the reoccurrence of severe seizures over a 10-year time period. According to the Centers for Disease Control and Prevention (CDC, 2019), the prevalence of active epilepsy in the United States was 1.2% in 2015. Research has revealed that up to 60% of people living with epilepsy (PWE) had associated depression, and a seizure frequency of >1 per month produced a 2.5 times increased risk of depression (Chandrasekharan, Menon, Wadwekar, & Nair, 2017). PWE have been found to develop depression and other mood disorders at a higher rate compared to individuals with no neurological diagnoses, prior to experiencing their first seizure. Research suggests that the structural components in the brain that make a person more susceptible to seizures also make that individual more susceptible to depression than the general population (Hesdorffer et al., 2012). When paired together, epilepsy and depression negatively affect the structural components of neural activity in the brain, causing individuals to experience increased levels of distress.

The brain is a complex system of nerve cells that are continuously communicating to carry-out the functions of the body ranging from simple tasks to intricate processes. The brain belongs to the central nervous system (CNS) responsible for relaying information between the spinal cord and the rest of the body. Nerve cells, known as neurons, are designed to transmit chemical and electrical signals from one end of the cell to the other (Lovinger 196). Neurons are termed “excitable” cells because of their ability to interact with charged particles, which are used to communicate between cells. Each neuron contains ion channels, allowing the transfer of small charged particles between the axon terminal of one neuron to the dendrite of the other (Lovinger, 2008). As information is collected from various surrounding neurons, if the threshold is reached, an action potential will be sent down the axon of a neuron. This passes the message on to the adjacent neuron where the process begins again. Neurons are designed to be continuously firing within the brain, PWE may experience an epileptic seizure when there is abnormal neuron activity such as a silence in neural communication. Immediately following a seizure, a depressive episode may be triggered, possibly lasting up to 2 weeks (Kanner, 2006).

According to Bertram (2013) in “Neuronal circuits in epilepsy: Do they matter?” seizures are a product of several circuits within the brain activating at the same time. Pandya, Altinay, Malone, and Anand (2012) determined that the pathophysiology of depression may be distributed across many regions and circuits of the brain similar to epilepsy. During an epileptic seizure, this sudden outburst of neural activity depletes energy that could be used on positive contributions resulting in inadequate brain functioning in the form of depression. Among a sample of 76 patients with epilepsy, 43% were found to have a major depressive disorder (MDD) (Kanner, 2006).  

It is important in the case of epilepsy and depression to properly identify and diagnose both disorders together, as failure to do so may result in various consequences for the patient. In “Depression and Epilepsy: A New Perspective on Two Closely Related Disorders,” Kanner (2006) states three possible consequences of a misdiagnosis: (1) Increased suicidality risk, (2) negative impact on quality of life, and (3) impact on costs and use of medical services. Patients suffering from both epilepsy and depression have been shown to have a higher rate of suicide compared to the general population. In a 2003 study, Jones et al. found the suicide rate of PWE to be 12% while only 1.1% in the general population.

The areas associated with the origin of a seizure are known as focus areas, which, if properly identified, can be targets for surgical removal. Epilepsy surgery is only recommended to patients whose focus areas do not conflict with a critical area of neural function, such as the ability of speech, movement, memory, or vision. The highest success rates are in cases whose abnormality on a magnetic resonance imaging (MRI) match the area identified on an electroencephalogram (EEG) monitoring system (Cascino & Britton, 2018).

For the best post-surgical outcome, both the epileptic seizures and depression must be affecting the same brain region or neural circuits. In a study by Shamim, Hasler, Liew, Sato, and Theodore (2009), it was determined that epilepsy and depression were associated with reduced hippocampal volumes. The hippocampus is located in the temporal lobe of the brain, which is known for its role in emotions. A type of neurosurgery aiding in the removal of the focus area of epileptic seizures is known as a lobectomy, and is typically conducted on the anterior temporal lobe (anterior temporal lobectomy). This has shown the highest success rate with 60-70% of patients being free of seizures that impair their consciousness or cause abnormal movements (Cascino & Britton, 2018). Although the surgery does not completely eliminate the chance of having seizures later on in life, it does significantly improve seizure control in PWE.

Although surgical operations can improve seizures in some individuals, it is seen as a last resort when considering treatment options for PWE and depression. Medication can be provided as a non-invasive means for regulating and controlling the symptoms of both epilepsy and depression. When looking at the two disorders separately, epilepsy can be treated with antiepileptic drugs whereas depression can be treated with antidepressant drugs. Since, depression and epilepsy are typically treated separately, it raises concerns when pairing prescription drugs together because drug interactions, side effects, and expenses are not well established (Noe, Locke, & Sirven, 2011). In therapeutic studies, antiepileptic drugs used as mood stabilizers showed positive results in patients with epilepsy and mild depressive symptoms (Miller, Kustra, Vuong, Hammer, & Messenheimer, 2008). For example, Miller, Kustra, Vuong, Hammer, and Messenheimer used valproic acid, lamotrigine and carbamazepine as the antiepileptic drugs over a 7 to 8 week study (2008). It is important to note there is a wide range of antiepileptic drugs; it is the job of a physician to determine the correct prescription and drug dosage for each individual patient.

As the brain is a highly sensitive organ, neurosurgery can threaten the integrity of other vital biological systems. Medication is the first treatment option used when treating epilepsy and depression as they present a lower risk of damaging the nervous system. Although, epilepsy is not directly associated with depression, there is strong evidence to suggest a linkage between the two disorders centralized around the temporal lobe. It is the role of the physician to properly diagnose a patient with epilepsy and depression when relevant. This diagnosis could save the patient from further pain and suffering. More research is needed on patients with both epilepsy and depression in order to properly treat the two disorders when diagnosed together. As technology advances, researchers will be able to precisely determine the neural circuits responsible for epilepsy and depression and target them for repair or removal.

References

Bertram, E. H. (2013). Neuronal circuits in epilepsy: Do they matter?. Experimental neurology, 244, 67-74. doi:10.1016/j.expneurol.2012.01.028.

Cascino, G. D., & Britton, J. W. (Oct. 2018). Types of epilepsy surgery. Epilepsy Foundation. Retrieved from https://www.epilepsy.com/learn/treating-seizures-and-epilepsy/surgery/types-epilepsy-surgery

Chandrasekharan, S. C., Menon, V., Wadwekar, V., & Nair, P. P. (2017). High frequency of depressive symptoms among adults with epilepsy: Results from a Hospital-based Study. Journal of neurosciences in rural practice, 8(Suppl 1), S13. doi:10.4103/jnrp.jnrp_21_17

Epilepsy prevalence in the United States 2019. (2019). Centers for Disease Control and Prevention. Retrieved from https://www.cdc.gov/epilepsy/data/index.html

Fisher, R. S., Acevedo, C., Arzimanoglou, A., Bogacz, A., Cross, J. H., Elger, C. E., ... & Hesdorffer, D. C. (2014). ILAE official report: a practical clinical definition of epilepsy. Epilepsia, 55(4), 475-482. doi:10.1111/epi.12550.

Hesdorffer, D. C., Ishihara, L., Mynepalli, L., Webb, D. J., Weil, J., & Hauser, W. A. (2012). Epilepsy, suicidality, and psychiatric disorders: a bidirectional association. Annals of neurology, 72(2), 184-191. doi:10.1002/ana.23601.

Jones, J. E., Hermann, B. P., Barry, J. J., Gilliam, F. G., Kanner, A. M., & Meador, K. J. (2003). Rates and risk factors for suicide, suicidal ideation, and suicide attempts in chronic epilepsy. Epilepsy & Behavior, 4, 31-38. doi:10.1016/j.yebeh.2003.08.019.

Kanner, A. M. (2006). Depression and epilepsy: a new perspective on two closely related disorders. Epilepsy currents, 6(5), 141-146. doi:10.1111/j.15357511.2006.00125.x

Lovinger, D. M. (2008). Communication networks in the brain: neurons, receptors, neurotransmitters, and alcohol. Alcohol Research & Health: the journal of the National Institute on Alcohol Abuse and Alcoholism, 31(3), 196-214.

Miller, J. M., Kustra, R. P., Vuong, A., Hammer, A. E., & Messenheimer, J. A. (2008). Depressive symptoms in epilepsy: Prevalence, impact, aetiology, biological correlates and effect of treatment with antiepileptic drugs. Drugs, 68(11), 1493-509.

Noe, K. H., Locke, D. E., & Sirven, J. I. (2011). Treatment of depression in patients with epilepsy. Current treatment options in neurology, 13(4), 371-379. https://doi.org/10.1007/s11940-011-0127-8

Pandya, M., Altinay, M., Malone, D. A., & Anand, A. (2012). Where in the brain is depression?. Current psychiatry reports, 14(6), 634-642. doi:10.1007/s11920-012-0322-7.

Shamim, S., Hasler, G., Liew, C., Sato, S., & Theodore, W. H. (2009). Temporal lobe epilepsy, depression, and hippocampal volume. Epilepsia, 50(5), 1067-1071. doi:10.1111/j.15281167.2008.01883.x.