By: Maura Toner
Depression and epilepsy have been clinically proven to be two closely related disorders with a highly bidirectional relationship. The comorbid relationship between epilepsy, anxiety, and depression is well documented. The National Institute of Health cites many epidemiological studies stating that there is a higher prevalence of depression and anxiety among people with epilepsy. Among people with epilepsy, roughly 9-37% suffer from depression and 11-25 percent suffer from anxiety. In fact, the NIH states that the reverse is also true; people with anxiety and depression are also clinically more likely to have epilepsy. The comorbid relationship of anxiety with depression inflates the effects of these disorders even further. Among people with epilepsy, around one in three people are either anxious, depressed, or both, making depression the most frequently occurring comorbid psychiatric disorder in epilepsy.
Depression in epilepsy most often presents as inter-ictal (between seizure) depression, with common symptoms including lack of enjoyment, low energy, reduced appetite, abnormal sleep patterns, and agitation. More severe symptoms include psychosis or impulsive self-harm. Pre-ictal depression may appear before a seizure; if this pattern occurs, a short acting benzodiazepine can be used to prevent seizures. Ictal (during seizure) depression is extremely rare but documented, with ictal anxiety more common.
Depression lowers the quality of life, regardless of having epilepsy or not, and is an easily treatable condition. Comorbid depression and epilepsy can have catastrophic effects on the body; failure to treat can lead to suicide, negative effects of epileptic medication worsen, and seizure frequency can increase if sleep deprivation is also present. Despite the known increased prevalence of depression among epileptics, doctors often fail to diagnose or are hesitant to treat patients, in fear of worsening or more frequent seizures. This is most often untrue, as some antidepressants can be taken with anticonvulsants.
People with epilepsy commonly have panic disorder, generalized anxiety-disorder, or seizure induced fear. Note that anxiety in epilepsy patients, like depression, can be ictal or inter-ictal. In fact, many studies conducted both in hospital and community settings find the prevalence of intere-ictal anxiety disorder to be around 10-25%. Anxiety is more difficult to diagnose as it often presents with similar signs to depression or occurs simultaneously within patients. People with panic disorder have panic attacks and an anticipatory fear of them that affects daily functioning. Generalized anxiety disorder patients, on the other hand, experience excessive worry and anxiety combined with restlessness, lack of concentration, irregular sleep patterns, fatigue, irritability and muscle tension, among others. The majority of people with epilepsy and anxiety are diagnosed with generalized anxiety disorder. It’s hypothesized that the onset of anxiety in epilepsy is due to the lack of control and erratic nature of seizures.
Many people with epilepsy have neither panic disorder nor generalized anxiety disorder, but have similar feelings of fear related to their seizures; fear is a common symptom of partial seizures in the temporal lobe, and therefore it is often difficult to distinguish between an anxious panic attack and this seizure symptom. Nevertheless, phobic disorders are very prevalent among people with epilepsy, stemming from poor seizure control and subsequent onset of social anxiety and feelings of being unsafe.
Sadly, anxiety and depression in epilepsy lead to ideation and attempt of suicide more often than in the general population. About 5% of people with epilepsy die by suicide, compared to 1.4% in the general population. Those that have epilepsy, are 25-49 years of age, have co-existing psychological or personality disorders, have temporal lobe epilepsy, uncontrolled seizures, prolonged epilepsy and/or personal/social/professional life difficulties are more at risk for suicide. Sadly, 80-90% of suicide attempts are overdoses.
Physiology
There are various areas of the brain associated with the pathophysiology of depression in people with epilepsy; these include the frontal, temporal, and limbic areas of the brain. More specifically, abnormalities in the monoamine pathways, glucose metabolism, interleukin-1b, among others, have been hypothesized as the pathogenesis for depression among epileptics. Anxiety, on the other hand, is linked to the amygdala and hippocampus; abnormalities with gamma-aminobutyric acid and serotonin are linked to its cause.
Medication: the common link
Both depression and anxiety may cause dark thoughts and suicidal ideation. Although these experiences are not common among people with both epilepsy and anxiety-depression, depressive thoughts may increase the adverse side effects associated with anti-epileptic drugs. In turn, these negative effects are linked to weak responses to surgery and pharmacological epilepsy treatments. Conversely, patients taking antiepileptic drugs may become depressed as a result of the medical treatment. The antiepileptic drugs most commonly associated with acute depression symptoms are vigabatrin, phenobarbitone, and topiramate.
Closing
Quality of life can be severely affected by the conditions of depression, anxiety, and epilepsy, especially in tandem with one another. Thus, timely recognition, diagnosis and treatment are absolutely crucial, which can be easily be done with polling and simple instruments in clinics. Surprisingly, there is very little research to date regarding the comorbid relationships of anxiety/depression or the efficacy of certain treatments. What is known, is that there are very easy steps to diagnose comorbid anxiety or depression in someone with epilepsy. Asking open ended questions and scaling thoughts and feelings are very helpful in diagnosis of depression and anxiety. Common tests are the PRIME-MD and the HAD scale for anxiety, for example. The patient completes the test, is scored, and there are clear cut offs for treatment.
Going forward, medical or psycho-behavioral therapies show promise for managing depression and anxiety with epilepsy, but well-designed randomized controlled trials have yet to be conducted. However, a pilot study for vagus nerve stimulation (VNS) as a potential treatment for major depressive disorder has shown promising results in gradual long term effects. The mental health of people with epilepsy should not be ignored, especially given that there is a much higher risk for anxiety and depression among this population. Countless studies have proven the existence of these comorbidities and provided evidence for anxiety and depression prevention, assessment, and treatment as crucial parts of epilepsy care.
Chronic, intermittent vagus nerve stimulation (VNS) has proven to be a safe, effective option for patients suffering from refractory seizures who are not candidates for surgical resection. Although only a small minority of patients will be entirely seizure-free, VNS as an adjunct to medical therapy does appear to provide a significant amount of improvement in quality of life. Reports of antidepressant effects independent of seizure control, along with the use of multiple AEDs in the treatment of depression, has led to the investigation of VNS as a potential adjunctive treatment for major depressive disorder. Both the number of severely depressed patients refractory to available pharmacologic options and the need for repeated treatments and significant side effects associated with electroconvulsive therapy have heightened the interest in VNS for this patient population. Pilot studies of VNS for depression have shown impressive response rates; however, the effect appears to be gradual in onset, as demonstrated by the lack of a favorable response in a short-term, randomized controlled study. Investigation is thus needed to establish the potential role of VNS as an adjunctive treatment for severe depression.
Resources:
Ałbena Grabowska-Grzyb, Joanna Jędrzejczak, Ewa Nagańska, Urszula Fiszer. Risk factors for depression in patients with epilepsy, Epilepsy & Behavior, Volume 8, Issue 2, 2006, Pages 411-417, ISSN 1525-5050, https://doi.org/10.1016/j.yebeh.2005.12.005.
Andrey M. Mazarati, Eduardo Pineda, Don Shin, Delia Tio, Anna N. Taylor, Raman Sankar. Comorbidity between epilepsy and depression: Role of hippocampal interleukin-1β, Neurobiology of Disease, Volume 37, Issue 2, 2010, Pages 461-467, ISSN 0969-9961. https://doi.org/10.1016/j.nbd.2009.11.001.
Depression in epilepsy, A systematic review and meta-analysis. Kirsten M. Fiest, Jonathan Dykeman, Scott B. Patten, Samuel Wiebe, Gilaad G. Kaplan, Colleen J. Maxwell, Andrew G.M. Bulloch, Nathalie Jette. Neurology Feb 2013, 80 (6) 590-599; DOI: 10.1212/WNL.0b013e31827b1ae0
Fuller-Thomson, E. and Brennenstuhl, S. (2009), The association between depression and epilepsy in a nationally representative sample. Epilepsia, 50: 1051-1058. https://doi.org/10.1111/j.1528-1167.2008.01803.x
Gnanavel S. (2017). Epilepsy and Depression: A Bidirectional Relationship. Journal of neurosciences in rural practice, 8(Suppl 1), S5–S6. https://doi.org/10.4103/jnrp.jnrp_203_17
Hoppe, C., Elger, C. Depression in epilepsy: a critical review from a clinical perspective. Nat Rev Neurol 7, 462–472 (2011). https://doi.org/10.1038/nrneurol.2011.104
Jackson MJ, Turkington D. Depression and anxiety in epilepsy. Journal of Neurology, Neurosurgery & Psychiatry 2005;76:i45-i47.
Kanner A. M. (2006). Depression and epilepsy: a new perspective on two closely related disorders. Epilepsy currents, 6(5), 141–146. https://doi.org/10.1111/j.1535-7511.2006.00125.x
Kwon, O. Y., & Park, S. P. (2014). Depression and anxiety in people with epilepsy. Journal of clinical neurology (Seoul, Korea), 10(3), 175–188. https://doi.org/10.3988/jcn.2014.10.3.175
Milby, A.H., Halpern, C.H. & Baltuch, G.H. Vagus nerve stimulation for epilepsy and depression. Neurotherapeutics 5, 75–85 (2008). https://doi.org/10.1016/j.nurt.2007.10.071
