Treatments for patients with comorbid epilepsy and depression: A systematic literature review

doi:10.1016/j.yebeh.2013.03.029

Epilepsy & Behavior

Volume 28, Issue 1, July 2013, Pages 36-40

https://doi.org/10.1016/j.yebeh.2013.03.029 Get rights and content

Highlights

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We studied patients with epilepsy and comorbid depression.
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We reviewed controlled clinical trials for treatment of epilepsy and depression.
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Antidepressants, oxcarbazepine and lamotrigine showed improvement in mood.
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Cognitive behavioral therapy improved both depression and epilepsy outcomes.
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Quality of life improves with treatment of depression among those with epilepsy.

Abstract

Depression is recognized as a serious comorbidity of epilepsy, but treatment of depression and anxiety in people with epilepsy is challenging. The aim of this article was to review published controlled clinical treatment studies of depression and anxiety in patients with epilepsy. The PubMed, Cochrane and PsycINFO databases were searched for controlled clinical trials, or controlled psychosocial or behavioral trials published in English before June 2012. Search terms were: seizures, epilepsy, depression, psychotherapy, cognitive therapy/treatment, behavioral therapy/treatment and nonpharmacologic therapy/treatment, education and stress management. Seven studies were included in this review. Interventions included antidepressant medications, antiepileptic medications, and cognitive behavioral therapy. Despite the methodological limitations in the studies identified by this review, both medications and psychotherapy improved depression and anxiety in patients with epilepsy. However, further research is needed in the form of randomized controlled clinical trials to establish appropriate pharmacological and psychosocial co-management of depression and epilepsy.

Introduction

Depression, often accompanied by anxiety, is widely recognized as a serious comorbidity of epilepsy. It not only contributes to a poorer quality of life but also adds greatly to medical costs [1]. Patients with epilepsy are at high risk of developing depressive symptoms [2], and suicide rates in patients with epilepsy have been reported to be up to ten times higher than in the general population [3]. Variable data exist in literature regarding the overall incidence of depression in patients with epilepsy; however, 30% is estimated to be the average [4], [5].

Depression in people with epilepsy is categorized into peri-ictal, ictal, post-ictal and inter-ictal types. The presence of dysphoric, depressive symptoms or anxiety that precedes the seizure and subsides with the ictus has been thought to represent peri-ictal depression. There is a paucity of data that support the neurobiological basis of this entity [6], [7].

Ictal depression has been commonly described in patients with temporal lobe epilepsy and an incidence of about 10% has been reported in this patient population in literature [8], [9], [10], [11]. Post-ictal depression is the second most common type of depression, seen with unilateral frontal or temporal foci, and is often attributed to the inhibitory mechanisms that result in cessation of seizure activity.

Episodes of major depression, dysthymia or affective mood disorder between seizures constitute inter-ictal depression [12]. It is the most common form of depression in patients with epilepsy [13], [14], [15].

Treatment of comorbid depression in people with epilepsy is challenging. There is a paucity of data regarding utilization of medical, behavioral or concomitant behavioral as well as medical management for treatment of depression in such patients. Psychotherapeutic approaches using cognitive behavioral therapy (CBT) has been demonstrated to be effective in patients with chronic somatic conditions [16]. Medical therapy for depression with selective serotonin reuptake inhibitors (SSRI) is often prescribed in spite of the absence of evidence-based guidelines [17], [18]. This is a systematic review of the published literature on prospective controlled trials on treatments of patients with epilepsy and comorbid depression. The review identified both medication and psychotherapy trials and concludes with a discussion of clinical implications of findings as well as recommendations for future investigations.

Section snippets

Methods

The PubMed, Cochrane and PsycINFO databases were searched for prospective controlled clinical trials, or controlled psychosocial or behavioral trials published in English before June 2012. Search terms used were seizures, epilepsy, depression, psychotherapy, cognitive therapy/treatment, behavioral therapy/treatment and nonpharmacologic therapy/treatment, education and stress management. A search of the MeSH database was also performed, using the terms epilepsy, seizures, depression, anxiety and

Types of studies

A total of eighteen articles were found in the systematic search. Eleven articles were found not to fit criteria by review of their abstracts and were excluded. Studies ranged in publication dates between 1985 and 2011. Three of the trials were medication trials while 4 trials used psychotherapies. Two of the articles were published from the same study by Chaytor et al. [19] highlighting immediate as well as long-term outcomes from the use of PEARLS (Program to encourage active, rewarding lives

Discussion

There is a paucity of data regarding treatment of patients with comorbid depression and epilepsy. Although recent years have seen emergence of more studies, few of these are randomized controlled clinical trials.

There are several factors that limit the generalizability of published studies to the general population of patients with seizures and depression. First, the sample sizes of trials were small and ranged from 17 to 80 patients. Women and ethnicities other than Caucasian were

Conclusion

In conclusion, our review suggests that medication and behavioral treatments can improve both depression and seizures in people with epilepsy and depression. Treating depressive symptoms generally results in better health outcomes. Further research is needed in the form of rigorous trials to establish appropriate pharmacological co-management of depression and epilepsy, standardize delivery of CBT formats, and establish consensus on measures for assessment of depression and other health

Conflicts of interest

The authors of this manuscript do not declare any conflict of interest for this review.

Acknowledgments

We appreciate the helpful assistance of Ms. Elisabeth Welter in manuscript preparation.

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The effect of meditation on brain activity has been the topic of many studies in healthy subjects and in patients suffering from chronic diseases. These effects are either explored during meditation practice (state effects) or as a longer-term result of meditation training during the resting-state (trait). The topic of this article is to first review these findings by focusing on electroencephalography (EEG) changes in healthy subjects with or without experience in meditation. Modifications in EEG baseline rhythms, functional connectivity and advanced nonlinear parameters are discussed in regard to feasibility in clinical applications. Secondly, we provide a state-of-the-art of studies that proposed meditative practices as a complementary therapy in patients with epilepsy, in whom anxiety and depressive symptoms are prevalent. In these studies, the effects of standardized meditation programs including elements of traditional meditation practices such as mindfulness, loving-kindness and compassion are explored both at the level of psychological functioning and on the occurrence of seizures. Lastly, preliminary results are given regarding our ongoing study, the aim of which is to quantify the effects of a mindfulness self-compassion (MSC) practice on interictal and ictal epileptic activity. Feasibility, difficulties, and prospects of this study are discussed.
Effect of alexithymia and difficulty of emotion regulation, neuroticism, low extraversion, and suicidality on quality of life in epilepsy
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Although there was no difference between the groups in terms of depression in our study. This situation differs from the literature [56–58]. In our patient group, most patients seem to have good seizure control, and the number of patients with drug-resistant seizures is low.
The objective of this study was to investigate alexithymia, emotion dysregulation, suicidality, and personality traits in people with epilepsy (PWE) and to evaluate their effects on quality of life.
Forty-six consecutive PWE and forty healthy control subjects (HC) were recruited for the study. Both PWE and HC were interviewed and completed the following questionnaires: Toronto Alexithymia Scale-20(TAS-20), Difficulties in Emotion Regulation Scale (DERS), Eysenck Personality Questionnaire, Suicidal Ideation Scale, Beck Depression Inventory-II, Beck Anxiety Inventory, and Quality Of Life In Epilepsy-31.
TAS-20 and difficulty identifying feelings which was the subgroup of TAS-20, scores of total and non-acceptance, goals, impulse, strategies, and clarity subgroups of DERS were statistically significantly higher in PWE (p = 0.01, 0.004, 0.01, 0.07, 0.009, 0.06, 0.01, respectively). Considering the personality characteristics, neuroticism was more common in PWE, while extraversion was less common. Suicidal ideation and anxiety scores were higher in PWE than HC (p = 0.02, p = 0.003). Anxiety, suicidal ideation, neuroticism, alexithymia and emotion dysregulation had a negative relationship on quality of life. (r = −0.54, p < 0.001; r = −0.54, p < 0.001; r = −0.62, p < 0.001; r = −0.32, p = 0.02; r = −0.52, p < 0.001).
Difficulty identifying feelings, dysregulation of emotions especially nonacceptance, goals, impulse, strategies, and clarity are common in PWE. Anxiety, suicidal ideation, neuroticism, alexithymia, and emotion dysregulation had a negative impact on quality of life. Each of these are important for psychosocial wellbeing of our patients and must be questioned considering their effects on quality of life.
Individuals who develop drug-resistant epilepsy within a year after initial diagnosis have higher burden of mental and physical diseases one-year prior to epilepsy diagnosis as compared to those whose seizures were controlled during the same interval
2021, Epilepsy and Behavior
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A recent survey revealed that the majority of clinicians treating patients with epilepsy felt inadequately resourced to manage these disorders and that there is a lack of trained specialists available [40]. Furthermore, limited evidence suggests antidepressants for the treatment of depression are effective for people with epilepsy [45–47], and clinical trials investigating the efficacy of these treatments and other treatments for mood disorders are lacking [41]. The high prevalence of mood disorder diagnoses and presence of suicidal thoughts and thoughts of self-harm observed in 2–4% of the newly diagnosed epilepsy and DRE cohorts, respectively, underscores the importance of continued screening and early identification of mood disorders and highlights the need for further investigation and education for practitioners on effective treatments for managing coexisting mood disorders.
Epilepsy is a neurological disease characterized by recurrent, unprovoked seizures and its impact on biological, cognitive, psychological, and social outcomes. An unmet need for finding effective treatment options exists. Identifying medical diagnoses present prior to a diagnosis of epilepsy is an important step in increasing our understanding of how people with epilepsy may respond to therapy, help guide clinicians in managing associated comorbid conditions, and inform future research.
A population-based retrospective comparative cohort study was conducted using administrative claims data to explore differences in medical diagnoses prior to an initial diagnosis of epilepsy between patients with and without drug-resistant epilepsy (DRE) identified within one-year post diagnosis by evaluating standardized mean differences between the groups.
A total of 205,183 patients with newly diagnosed epilepsy were identified. Of those, 4.1% (n = 8340) were considered drug resistant one-year post diagnosis. Pain and mood disorders were the common physical and psychiatric diagnoses in both cohorts. Differences between the newly diagnosed epilepsy and DRE cohorts were observed. Patients in the DRE cohort were younger, had more encounters with the healthcare system, and higher burden of disease for both physical (e.g., headache, neuropathy, muscular-skeletal disorders, and traumatic brain injury) and psychiatric diagnoses (e.g., depression, anxiety, bipolar disorder, suicidal thoughts, drug dependency, and sleep disorders).
Physical and psychiatric diagnoses are common one year prior to first diagnosis of epilepsy in administrative claims data. Compared to patients without DRE, those who develop DRE within one-year post initial diagnosis demonstrated a higher burden of disease.
Group-based cognitive behavioral therapy program for improving poor sleep quality and quality of life in people with epilepsy: A pilot study
2020, Epilepsy and Behavior
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Moreover, specific CBT-I techniques could arguably be a part of standard care in patients with epilepsy [8,11,43–47]. Although CBT has been shown to improve quality of life in patients with epilepsy [48–54], its effect on sleep difficulties in this population remains unknown. Given that patients with epilepsy exhibit factors that perpetuate sleep disturbance and the success of CBT-I in other populations, it seems feasible to apply CBT-I to this clinical population.
Sleep difficulties are commonly reported by patients with epilepsy and can have a detrimental impact on overall quality of life. The purpose of this pilot study was to assess the efficacy of a psychotherapeutic approach, namely Cognitive Behavioral Therapy for Insomnia (CBT-I), in improving sleep quality in patients with epilepsy. Twenty outpatients with epilepsy who reported poor sleep quality were randomized to either a control or CBT-I treatment group, which involved four group-based CBT-I sessions, delivered on a weekly basis. In addition to completing a range of standardized measures related to sleep quality and quality of life, participants also monitored their sleep with a self-completed sleep diary over a two-week period, on two separate occasions. Following CBT-I treatment, no between-group difference was found on any sleep or quality of life measure. However, both the treatment and control groups improved on measures of sleep quality, quality of life, sleep hygiene behaviors, and dysfunctional beliefs about sleep. These findings suggest that sleep monitoring alone may have the potential for prompting healthy behavior change in this clinical population.
Do distance-delivery group interventions improve depression in people with epilepsy?
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The causes of depression in people with epilepsy are believed to be multifactorial, with both neurobiological factors (e.g., abnormal neural substrate, seizures, antiseizure medications, family history of mental health issues) and psychosocial determinants (e.g., constant worry related to the unpredictable nature of seizures, social isolation, unemployment, low self-esteem, stigma) [2,3]. Both medications and psychotherapy have been shown to be effective in reducing depressive symptoms [4–6]. In particular, distance-delivery therapeutic interventions have been shown to be beneficial in people with epilepsy [7,8].
About one-third of people with epilepsy experience comorbid depression. The present study examined outcomes of a distance-delivery group intervention program designed to improve emotional well-being. Participants were 55 adults with epilepsy and self-reported depressive symptoms who were randomly assigned to take part in either a mindfulness-based cognitive behavioral therapy (CBT) program (UPLIFT, n = 20), an epilepsy information and self-management program (EpINFO, n = 24) that served as an active control group, or a wait-list control (WLC) group (n = 11). The Quick Inventory of Depressive Symptomatology (QIDS), Neurological Disorders Depression Inventory for Epilepsy (NDDIE), and the psychological health subscale of the World Health Organization Quality of Life (WHOQOL-BREF) scale were used to assess depression and psychological quality of life before and after treatment, and at short-term (six months) and long-term follow-up (one year) upon program completion. From pre- to posttreatment, a main effect of time was found, with participants in both the UPLIFT and EpINFO groups having reported to a similar degree a significant decrease in depressive symptoms and improved psychological health, improvements that were not seen in the WLC group. The time by group interaction effect was not significant. The effects seen at posttreatment in the UPLIFT and EpINFO groups remained at six months and one year after treatment. These data suggest that distance-delivery group intervention programs are effective at improving depression and psychological quality of life, with the EpINFO program offering benefits similar to the UPLIFT program.
Depression in people with epilepsy in West China: Status, risk factors and treatment gap
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To evaluate the prevalence, suicidality and treatment gap (TG) of depression in people with epilepsy (PWE) in West China, and to explore the related risk factors.
A consecutive cohort of PWE from West China Hospital was recruited. The Chinese version of the Neurological Disorders Depression Inventory for Epilepsy scale was used to assess depression and suicidality. Prevalence and TG of depression were calculated. Logistic regression analysis was used to assess risk factors of depression and suicidality.
Among a total of 461 participants, there were 29.9% with depression and 15.8% had suicidality. Being female, an unmarried status, disease course, seizure frequency, seizure occurrence in the last 6 months, and focal impaired awareness seizure were risk factors for depression. Depression was an independent risk factor for suicidality. The TG of depression was 72.5%. The TG was larger in the 30–40 year age group, in rural populations, and among those with a disease course between 5 and 10 years. The TG figures dropped with increasing annual family income.
The prevalence of depression and the rate of suicide risk for PWE in West China are high. A large TG for depression exists in PWE. Clinicians should focus on depression and suicidality for PWE and identify the related risk factors in a timely manner so as to reduce the incidence of depression and suicide. Management including public education as well as professional training of neurologists are necessary to fill the TG.

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ReviewTreatments for patients with comorbid epilepsy and depression: A systematic literature review

Highlights

Abstract

Introduction

Section snippets

Methods

Types of studies

Discussion

Conclusion

Conflicts of interest

Acknowledgments

Epilepsy Res

Epilepsy Behav

Epilepsy Behav

Epilepsy Behav

Epilepsy Behav

Epilepsy Behav

Epilepsy Behav

J Affect Disord

Epilepsy Behav

Epilepsy Behav

Epilepsy Behav

Epilepsy Behav

Epilepsy Behav

Behav Res Ther

Eur Psychiatry

Lancet

Epilepsy and employment. A community based survey in an area of high unemployment

J Neurol Neurosurg Psychiatry

Psychiatric comorbidity in chronic epilepsy: identification, consequences, and treatment of major depression

Epilepsia

Depression in epilepsy. Relationship to seizures and anticonvulsant therapy

J Nerv Ment Dis

Psychopathology in epilepsy

Br J Psychiatry J Ment Sci

Psychic phenomena in partial seizures

Semin Neurol

Review
Treatments for patients with comorbid epilepsy and depression: A systematic literature review