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  • Updated 05.10.2023
  • Released 09.16.2014
  • Expires For CME 05.10.2026

Depressive disorders in epilepsy



Mood and anxiety disorders are the most common psychiatric comorbidities in patients with epilepsy. The prevalence rates of mood disorders have varied widely in the literature based on diversity in methodologies and sample populations across studies. Major depressive episodes are the most frequently identified mood disorders. In a meta-analysis by Fiest and colleagues, the prevalence was 23.1%; it was 22.9% and 21.9% in two subsequent meta-analyses (33; 106). Mood disorders are more common in females with and without epilepsy (38).

Its prevalence has been underestimated due to the underreporting of depressive episodes by patients and families and under-recognition by clinicians, starting with the failure of neurologists to investigate the existence of these common comorbidities during the initial evaluation or even throughout the course of treatment (62; 104). Several studies have established a higher prevalence of depressive disorders in patients with epilepsy than in healthy controls (80; 14) and people with chronic medical disorders (53; 113). Furthermore, population-based studies have established the existence of a bidirectional relationship between epilepsy and depression (49; 47; 46; 57).

There is an ongoing debate as to whether depression in patients with epilepsy differs from that in people with primary mood disorders (58). Proponents of both schools of thought are probably correct as a significant percentage of patients can experience any of the various forms of primary mood disorders, including major depressive disorder, dysthymic disorder, bipolar disorder, and cyclothymic disorder indistinguishable from those described in the Diagnostic and Statistical Manual of Mental Disorder (DSM), fifth edition (04). By the same token, several authors have identified atypical clinical manifestations of mood disorders that fail to meet any of the diagnostic criteria suggested in the various editions of the DSM in a significant proportion of patients with epilepsy (97; 64; 27). Kraepelin and Bleuler were the first to recognize a “unique” clinical presentation of mood disorders consisting of recurrent episodes of “dysphoric symptoms” in patients with epilepsy (87). Gastaut expanded on Kraepelin’s initial observations, and Blumer coined the term “interictal dysphoric disorder” (12; 89).

The purpose of this article is to provide a comprehensive review of mood disorders in adults with epilepsy, with special attention to epidemiologic and clinical data; the underlying pathogenic mechanisms, including common pathogenic mechanisms that may be operant in depression and epilepsy; and the basic principles of their treatment.

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. The scientific evidence supports the expression of the existence of common pathogenic mechanisms operant in both disorders and explains why patients with depression have a 2- to 5-fold higher risk of developing epilepsy and more than 20% of patients with epilepsy suffer from depression (59).

• 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 been 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 last 30 years. 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 (11). 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 (88).

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