Elsevier

Biological Psychiatry

Volume 54, Issue 3, 1 August 2003, Pages 388-398
Biological Psychiatry

Mood disorders and medical illness
Depression in epilepsy: prevalence, clinical semiology, pathogenic mechanisms, and treatment

https://doi.org/10.1016/S0006-3223(03)00469-4Get rights and content

Abstract

Depression is the most frequent comorbid psychiatric disorder in epilepsy. Its lifetime prevalence has been estimated at between 6% and 30% in population-based studies and up to 50% among patients followed in tertiary centers. The risk of suicide has been estimated to be 10 times higher than that in the general population. Although no one questions that epilepsy is a risk for depression, recent studies have also revealed that a history of depression is associated with a 4- to 6-fold greater risk of developing epilepsy. These data suggest either a possible “bi-directional” relationship between these two disorders or the presence of common pathogenic mechanisms that facilitate the occurrence of one in the presence of the other. The clinical presentation of depressive disorders in epilepsy can be identical to that of nonepileptic patients and can include major depression, bipolar and dysthymic disorders, and minor depression. In a significant percentage of cases, however, the clinical features of depression in epilepsy fail to meet any of the DSM-IV Axis I categories. Depression in epilepsy may be iatrogenically induced with various antiepileptic drugs used to treat the seizure disorder or after surgical treatment of intractable epilepsy. Despite its relatively high prevalence, depression remains unrecognized and untreated, and unfortunately its treatment is based on empirical and uncontrolled data.

Introduction

Depression is the most common comorbid psychiatric condition associated with epilepsy; yet its actual incidence and prevalence remain to be established. The diversity in methodologies and sample populations across studies, the under-reporting of symptoms of depression by patients and families, and the under-diagnosis by clinicians are three of the principal causes accounting for the absence of these data. There is a consensus among various authors, however, that the prevalence of depression in epilepsy is higher than in a matched population of healthy control subjects, ranging from 20% to 55% in patients with recurrent seizures and from 3% to 9% in patients with controlled epilepsy Baker et al 1996, Edeh and Toone 1987, Indaco et al 1992, Jacoby et al 1996, Lambert and Robertson 1999, Mendez et al 1986, O’Donoghue et al 1999, Robertson and Trimble 1983.

A study of concerns of living with epilepsy found that about one third of patients spontaneously report mood as a significant problem (Gilliam et al 1997). Four of the largest studies are reviewed briefly here to provide representative data. In a community-based study that used the Hospital Anxiety and Depression Scale, Jacoby et al (1996) observed in a large survey that 21% of 168 patients with recurrent seizures were depressed. More recently, O’Donoghue et al (1999) used the same scale to demonstrate that, of a group of 155 patients identified through two large primary care practices in the United Kingdom, 33% with recurrent seizures and 6% of those in remission had depression. Using the Clinical Interview Schedule, Edeh and Toone (1987) found a depressive disorder in 22% of 88 epilepsy patients identified from general practices in the United Kingdom. At the 2002 Annual Meeting of the American Academy of Neurology, Blum reported the results of a population-based survey that investigated a lifetime prevalence of depression, epilepsy, diabetes, and asthma in nearly 181,000 individuals. Among the 2281 people with epilepsy, 29% reported having experienced at least one episode of depression. This contrasted with 8.7% prevalence in healthy respondents and with 17% and 16% in patients with diabetes and asthma, respectively. The lack of gender difference in the prevalence rates of depression among patients with epilepsy is worth noticing. Furthermore, 9.8% of these patients reported symptoms of manic-depressive illness. These findings were surprising because manic symptoms in epilepsy have frequently been quoted as being rare Barczak 1988, Byrne 1988, Morphew 1988, O’Shea 1988. Wolf (1982) reported nine cases in his literature review and added six others, most related to the peri-ictal state or to an improved seizure control. Robertson et al (1987) reported 42 cases in his literature search, and there have been several case reports noting an association with a peri-ictal occurrence Barczak 1988, Byrne 1988, Morphew 1988, O’Shea 1988.

Although no one questions the higher prevalence in patients with epilepsy compared with healthy control subjects, there is continuous debate as to whether depression is more frequent among patients with epilepsy than in patients with other neurologic disorders Altshuler 1991, Dodrill and Batzel 1986. Indeed, four controlled studies comparing the prevalence of depression between patients with epilepsy and patients with other neurologic diseases, including traumatic brain injury, neuromuscular diseases, and multiple sclerosis, failed to show any difference in the rates of depression Altshuler 1991, Dodrill and Batzel 1986, Metcalfe et al 1988, Standage and Fenton 1975, although, for the most part, both groups seem to be at increased risk for depression compared with healthy control subjects. Three controlled studies suggest that epileptics have a higher rate of depression than do patients with nonepileptic neurologic diseases Altshuler 1991, Kogeorgos et al 1982, Mendez et al 1993. In a review of the literature, Dodrill and Batzel (1986) compared the prevalence rates of depression among patients with epilepsy with those of patients with neurologic (other than epilepsy) and nonneurologic illness and found increased rates of depression in epilepsy as compared with nonneurologic disorders but equal rates of depression in epilepsy and neurologic disorders.

In a recent review of the literature, Gilliam and Kanner (2002) concluded that suicide has one of the highest standardized mortality rates (SMR) of all causes of death in persons with epilepsy. Robertson (1997) reviewed 17 studies pertaining to mortality in epilepsy and found that suicide was 10 times more frequent than in the general population. Rafnsson et al (2001) recently reported the results of a population-based incidence cohort study from Iceland, in which suicide had the highest SMR (5.8) of all causes of death. A Swedish study found an SMR of 3.5 among 9000 previously hospitalized patients with epilepsy (Nilsson et al 1997).

Section snippets

How close is the relationship between epilepsy and depression?

Based on the evidence presented above, no one would doubt that epilepsy increases the risk of suffering from depression. But is the relationship between epilepsy and depression unidirectional? Three population-based, controlled studies published in the last decade seem to suggest a possible bidirectional relationship between these two disorders. In a population-based, case–control study of patients with newly diagnosed, adult-onset epilepsy carried out in Sweden, Forsgren and Nystrom (1990)

The different faces of depression in epilepsy

Depressive disorders can be classified according to the temporal relationship between the onset of psychiatric symptomatology and seizure occurrence into ictal (the depressive symptoms are a clinical manifestation of the seizure), peri-ictal (symptoms precede and/or follow the seizure occurrence), and interictal (symptoms occur independently of the seizure occurrence). Interictal depression is the most frequently “recognized” type of mood disorder and can present as major depression, bipolar

Impact of depression on quality of life

Perrine et al (1995) studied 257 epilepsy patients to determine the relationship of neuropsychological function to health-related quality of life. The independent neuropsychological variables included mood, verbal memory, psychomotor function, visual–spatial function, language, and cognitive inhibition. The mood factor had the highest correlations with scales of the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) and was the strongest predictor of poor quality of life in regression

Depression is more than a reactive process to epilepsy

As stated above, clinicians and patients alike have the misperception that “it is normal to feel depressed” when you suffer from epilepsy. Accordingly, patients do not seek treatment for these symptoms, and clinicians do not inquire about them. Although we do not deny a reactive process to facing the multiple obstacles associated with a life with epilepsy, its impact is mostly prevalent in the initial stages of the disease and levels off with time. The psychosocial factors that patients with

Treatment of depression in epilepsy

As mentioned above, the treatment of depression in epilepsy remains “unexplored territory,” despite its relatively high prevalence. The treatment of these patients has been, for all intents and purposes, empiric, based on the untested assumption “that patients with depression and epilepsy should respond to antidepressant drugs in the same manner as depressed nonepileptic patients.” In fact, there has only been one double-blind, placebo-controlled study published to date (22 years ago, in 1979!)

Conclusions

Depression is a relatively frequent and important comorbidity of epilepsy that has a significant negative impact in the quality of life of epileptic patients. The possible bidirectional relationship between these two disorders or the existence of common pathogenic mechanisms may also explain the efficacy of antiepileptic drugs in the treatment of patients with affective disorders. Given these data and given that a higher prevalence of depression has been consistently identified among patients

Acknowledgements

Aspects of this work were presented at the conference, “The Diagnosis and Treatment of Mood Disorders in the Medically Ill,” November 12–13, 2002 in Washington, DC. The conference was sponsored by the Depression and Bipolar Support Alliance through unrestricted educational grants provided by Abbott Laboratories, Bristol-Myers Squibb Company, Cyberonics, Inc., Eli Lilly and Company, Forest Laboratories, Inc., GlaxoSmithKline, Janssen Pharmaceutica Products, Organon Inc., Pfizer Inc, and Wyeth

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