Depressive disorders in epilepsy

Andres M Kanner MD (Dr. Kanner of the University of Miami, Miller School of Medicine has no relevant financial relationships to disclose.)
Maria Raquel Lopez MD (Dr. Lopez of the University of Miami, Miller School of Medicine has no relevant financial relationships to disclose.)
Jerome Engel Jr MD PhD, editor. (Dr. Engel of the David Geffen School of Medicine at the University of California, Los Angeles, has no relevant financial relationships to disclose.)
Originally released September 16, 2014; updated August 4, 2017; expires August 4, 2020


The authors provide a summary of the most common manifestations and complications and review the basic principles of management of depressive disorders in epilepsy. They review some of the pivotal aspects of the pathophysiology and highlight common pathogenic mechanisms that may be operant in epilepsy and depressive disorders, which may explain the bidirectional relationship that exists between these conditions.

Key points


• Depressive disorders are the most frequent psychiatric comorbidity in patients with epilepsy.


• Depression in patients with epilepsy can present with atypical clinical manifestations that fail to meet diagnostic criteria included in the Diagnostic and Statistical Manual of Mental Disorders.


• Depressive disorders are likely to worsen the quality of life of patients with epilepsy, increase the suicidal risk of patients, worsen their tolerance of antiepileptic drugs, and increase the economic burden on their family and society.


• Patients with epilepsy and a comorbid depression are more likely to suffer from treatment-resistant epilepsy, and patients with temporal lobe epilepsy undergoing epilepsy surgery are less likely to achieve full remission of auras following epilepsy surgery.


• A bidirectional relationship exists between depressive disorders and epilepsy, which is probably the expression of the existence of common pathogenic mechanisms operant in both disorders and explains the high comorbidity of the two conditions.


• The treatment modalities used in the management of primary depressive disorders can be applied to the management of patients with epilepsy.

Historical note and terminology

The close and complex relationship between depressive disorders and epilepsy has recognized for 26 centuries, when Hippocrates wrote: “melancholics become epileptics and epileptics melancholics.” In that statement, Hippocrates suggested the existence of a bidirectional relationship between the two disorders whereby “having depression increases the risk of developing epilepsy and vice-versa.” This observation was confirmed in population-based studies performed in the 20th and 21Ist centuries. The advent of modern psychiatry recognized the clinical similarities between depressive disorders of patients with epilepsy and primary depressive disorders. Yet, in 1923 Kraepelin suggested that depressive disorders in patients with epilepsy could also have a pleomorphic presentation that included symptoms of depression, anxiety, irritability, and pain as well as hypomanic symptoms, all of which increased in severity during the peri-ictal period (eg, preceding or following a seizure). These observations were confirmed by Bleuler in the 1940s and Gastaut 10 years later. Blumer coined the term of “interictal dysphoric disorder of epilepsy” to describe this form of depression in patients with epilepsy (Blumer and Altshuler 1998). Other authors have suggested that this form of depression is not specific to patients with epilepsy, as it has been identified in patients with migraine (Mula et al 2008).

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