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Comorbidities and complications of epilepsy in adults

Comorbidities and complications of epilepsy in adults
Author:
Steven C Schachter, MD
Section Editor:
Paul Garcia, MD
Deputy Editor:
John F Dashe, MD, PhD
Literature review current through: Jan 2024.
This topic last updated: Aug 03, 2023.

INTRODUCTION — Epilepsy is a chronic disease associated with an increased risk of a variety of psychiatric and medical comorbidities that can adversely affect quality of life as well as life expectancy. Comorbidities can arise due to common underlying predispositions, direct effects of seizures, underlying epilepsy etiologies, and adverse effects of antiseizure medications and other therapies. Depression and anxiety are particularly common in adults with epilepsy, and screening should be a routine part of long-term follow-up.

The most common comorbidities and complications of epilepsy in adults are discussed here. An overview of the management of epilepsy is presented separately. (See "Overview of the management of epilepsy in adults".)

PSYCHOSOCIAL ISSUES — Management of patients with epilepsy must include consideration of the psychosocial dimensions of the disorder [1,2]. In addition to medical and psychiatric comorbidities, patients with epilepsy suffer from loss of independence, underemployment, poorer social status, decreased leisure time, and decreased physical activity compared with unaffected adults [3-6].

Employment status is often negatively impacted by epilepsy, even when seizures are infrequent [7-9]. In one survey, more than 40 percent of college-educated people with seizures that were deemed well controlled were unemployed [7].

Newly diagnosed patients with epilepsy are commonly affected by the loss of independence that is most obvious in their inability to drive. They may also have problems obtaining insurance and finding or maintaining suitable employment. Their self-esteem may also suffer [10]. As the treatment plan is formulated, psychosocial issues must be systematically explored with patients so that appropriate referrals for additional help and counseling can be initiated.

Patients with epilepsy are more likely to have a poor pattern of health-related behaviors (eg, less physical activity and increased rates of smoking, alcohol consumption, and substance use disorders) compared with the general population [11-15]. Counseling regarding these issues may improve health and quality of life.

A complete psychosocial history includes inquiries about educational background, employment, driving, insurance, interpersonal relationships, previous psychiatric illness (especially depression), and attitude toward having epilepsy. Questionnaires for this purpose are available, and they provide a measurable way of assessing and following patients as pharmacotherapeutic and psychosocial interventions are implemented [16].

Identifying sources of psychosocial stress should lead to the development of strategies to minimize the impact of those stresses on the patient. Patients are often deeply concerned about health, independence, personal growth, relationships, well-being, and security; those with stress-induced seizures may be candidates for stress reduction, biofeedback, or relaxation training. Although direct evidence is limited, psychologic interventions may be of some benefit [2,17-19]. As an example, a randomized trial of 60 patients with drug-resistant epilepsy found that mindfulness-based therapy improved quality of life, depressive and anxiety symptoms, and seizure frequency compared with social support [17].

Many resources are available to help patients. In the absence of a local epilepsy group, patients should be encouraged to contact a regional or national epilepsy organization such as the Epilepsy Foundation (https://www.epilepsy.com/).

PSYCHIATRIC DISORDERS — A variety of psychiatric disorders, in particular depression and anxiety, occur with increased frequency among people with epilepsy. Recognition and treatment of comorbid psychiatric disease is critical to holistic care of people with epilepsy.

Depression and anxiety

Prevalence and risk factors — Mood disorders, particularly anxiety and depression, are common in patients with epilepsy [5,11,20-25]. The reported prevalence of depression in patients with epilepsy ranges from 13 to 35 percent, with much of the variability explained by differences in methods of ascertaining depression [26]. Rates are even higher among patients with uncontrolled epilepsy. In one community health survey, epilepsy was associated with 43 percent higher odds of depression after adjustment for other demographic factors [21]. Results from surveys in Canada and England have also reported higher odds of anxiety, depression, and suicidal ideation among those with epilepsy [22,27].

Risk factors for depression in people with epilepsy include epilepsy-related disability, unemployment and activity restriction, impaired social support, older age, female sex, low education level, anxiety, poor antiseizure medication adherence, and a perceived stigma associated with the diagnosis [28,29]. Other reports that find a high rate of psychiatric comorbidity (including depression, bipolar disease, psychosis, anxiety, and suicidality) predating seizure onset suggest a bidirectional relationship and perhaps a common underlying mechanism for psychiatric disorders and epilepsy [30,31].

Adverse effects of antiseizure medications and other medications should not be overlooked as a contributing factor to mood disorders. Antiseizure medications that may have negative effects on mood include phenobarbital, topiramate, tiagabine, gabapentin, levetiracetam, clobazam, zonisamide, and perampanel [32]. Polytherapy and a personal or family history of mood disorders or alcoholism are also risk factors for antiseizure medication-induced depression [29,33].

Mood disturbances are important contributors to decreased health-related quality of life [20,34-38]. One study suggested that the presence of a mood disorder also increases the likelihood of an antiseizure medication-related adverse event, which may, in turn, contribute to drug intolerance and nonadherence as well [39].

Suicide risk — Suicide risk is a particular concern in patients with epilepsy [40,41]. Suicidal ideation can occur as part of an interictal mood disorder or as postictal symptomatology [33].

A population-based study in Denmark demonstrated a three-fold higher risk for suicide in patients with epilepsy compared with controls [42]. Similar risk was demonstrated in a separate population-based study both in the three years before and after a diagnosis of epilepsy [31].

The risk of suicide is elevated in patients with and without known psychiatric comorbidity [25,43-45], although psychiatric comorbidities are underdiagnosed in patients with epilepsy. The risk is not fully explained by use of antiseizure medications, which have been associated with an increased risk of suicidality [46]. Additional risk factors may include male sex, temporal lobe epilepsy, and high seizure frequency [44,45,47]. (See "Overview of the management of epilepsy in adults", section on 'Side effects of therapy'.)

Screening — Given the high prevalence of mood disorders in epilepsy, patients should be screened as part of regular follow-up. International consensus group guidelines for the management of depression and other psychiatric conditions associated with epilepsy include the following recommendations [2,48]:

Patients should be screened for depression at diagnosis of epilepsy, prior to and following antiseizure medication initiation or changes, and at routine follow-up (eg, yearly). The Patient Health Questionnaire-9 (table 1) and Neurological Disorders Depression Inventory for Epilepsy are suggested tools. Both are publically available and have been validated in adults with epilepsy [49,50]. (See "Using scales to monitor symptoms and treat depression (measurement based care)" and "Screening for depression in adults", section on 'Screening tests'.)

Because of the risk of suicide as well as the adverse impact of depression on quality of life and seizure control, patients who screen positive for depression should receive appropriate evaluation and treatment of depression rather than watchful waiting. This may be accomplished in collaboration with the primary care provider or through referral to a mental health clinician, depending on the severity of the psychiatric symptoms and comfort level of the treating clinician. (See "Unipolar depression in adults: Assessment and diagnosis" and "Unipolar major depression in adults: Choosing initial treatment".)

Patients with epilepsy should be advised about the risk of suicide associated with epilepsy and antiseizure medication therapy. Although clinicians may worry at times that asking about suicide will prompt suicidal thoughts or actions, there are no data to support this concern, and patients may not verbalize suicidal feelings without being prompted. Patients with suicidal ideation should be referred for appropriate intervention. (See "Suicidal ideation and behavior in adults".)

Anxiety is a common comorbid condition in patients with epilepsy, and patients may benefit from specific treatment. The generalized anxiety disorder seven-item (GAD-7) scale (table 2) is easy to administer and has been validated in people with epilepsy [51]. (See "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis" and "Generalized anxiety disorder in adults: Management".)

Treatment considerations — Mood-altering effects of antiseizure medications should not be overlooked in patients who have developed depression or anxiety in a temporal relationship to new or discontinued medications. Iatrogenic causes of worsening mood symptoms in people with epilepsy include:

Discontinuation of a medication with mood-stabilizing effects (eg, carbamazepine, lamotrigine, valproate)

Withdrawal of medications with anxiolytic properties (eg, benzodiazepines, phenobarbital, gabapentin, pregabalin)

Introduction or rapid dose increase of an antiseizure medication with negative psychotropic properties, such as clobazam, phenobarbital, topiramate, vigabatrin, tiagabine, gabapentin, levetiracetam, zonisamide, or perampanel

Addition of an enzyme-inducing antiseizure medication in a patient who is taking an antidepressant that is hepatically metabolized

Absent reversible factors such as medication side effects, people with epilepsy and depression or anxiety should be managed similarly to the general adult population. Barriers to effective depression treatment in people with epilepsy include lack of access to psychiatric care, reluctance to accept the diagnosis or take more medication, and prior experience with therapy that was seen as unhelpful [33,52,53].

A common misconception is that all antidepressants lower the seizure threshold and should be avoided; these fears are largely associated with overdose and have little merit when antidepressants are used in a therapeutic range [32,54]. Potential exceptions include bupropion, clomipramine, amoxapine, and maprotiline [33].

Selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine have at least some direct evidence of efficacy in people with epilepsy [55,56] and are good options because they are unlikely to worsen seizure frequency and have minimal interactions with most antiseizure medications. Some SSRIs and SNRIs and most tricyclic antidepressants have effects on cytochrome P450 (CYP) isozymes that can alter metabolism of some antiseizure medications; specific interactions may be determined by use of the drug interactions program within UpToDate. Among the SSRIs, citalopram and escitalopram may have the fewest effects on the CYP system.

Psychotherapy for depression in patients with epilepsy is underutilized but has been shown to be effective in several randomized trials [54,57].

Epilepsy is not an absolute contraindication to electroconvulsive therapy (ECT), which has been used with success in small case series of patients with treatment-refractory depression and epilepsy [58,59]. The two major considerations in patients with epilepsy are the potentially higher risk for prolonged seizure and the impact of antiseizure medications on seizure threshold [58]. Patients with recent seizures or a history of status epilepticus should be closely monitored and maintained on antiseizure medications during ECT. Withholding a dose the night before or morning of ECT may be considered in patients without recent seizures if seizures are difficult to elicit during ECT. (See "Overview of electroconvulsive therapy (ECT) for adults" and "Medical evaluation for electroconvulsive therapy", section on 'Coexisting neurologic and neurosurgical disease'.)

The treatment of depression and anxiety are discussed in detail separately. (See "Unipolar major depression in adults: Choosing initial treatment" and "Generalized anxiety disorder in adults: Management".)

Psychotic disorders — The incidence of psychotic disorders is two- to threefold higher in patients with epilepsy compared with the general population [27,60,61], and the pooled prevalence rate of psychosis in patients with epilepsy is 5.6 percent [62]. In addition to comorbid primary psychiatric disorders such as schizophrenia, psychotic disorders may be related to epilepsy itself (ie, interictal psychosis, postictal psychosis) or secondary to antiseizure medications [63,64].

In a single-center review of over 2600 adults with epilepsy, the prevalence of psychotic disorders was 3.7 percent [65]. Among 98 patients with psychotic disorders, the most common diagnoses were interictal psychosis of epilepsy (34 percent), postictal psychosis (26 percent), comorbid schizophrenia/schizophreniform disorder (19 percent), and antiseizure medication-induced psychotic disorders (14 percent). Levetiracetam was the most commonly implicated antiseizure medication, temporally related to the onset of psychosis in 10 of 14 cases; other implicated drugs were topiramate, lamotrigine, and withdrawal of valproate. Risk factors for drug-induced psychosis were female sex and temporal lobe involvement; concurrent treatment with carbamazepine appeared to be protective against development of psychosis.

Patients with temporal lobe epilepsy are at increased risk for postictal psychosis, accounting for approximately 75 percent of all cases [66,67]. They may also make up a disproportionate number of patients with interictal psychosis, although the relationship is weaker [68]. Postictal psychosis usually begins within 48 to 72 hours of a seizure or cluster of seizures, following a lucid interval. Postictal psychosis is often associated with positive symptoms including paranoid or referential delusions, hallucinations, and aggression, whereas interictal psychosis may be more likely to manifest with disorganization and negative symptoms [66,69-71]. An electroencephalogram (EEG) can be helpful to assess for ongoing subclinical seizures that may be contributing to symptoms.

Patients with epilepsy and psychosis should be managed similarly to other patients with psychotic disorders. Most patients with antiseizure medication-induced psychosis will improve with discontinuation of the offending drug, although some patients may require short-term treatment with an antipsychotic drug [65]. The initial evaluation and management of psychosis is reviewed in detail elsewhere. (See "Psychosis in adults: Epidemiology, clinical manifestations, and diagnostic evaluation".)

Psychogenic nonepileptic seizures — Epilepsy and psychogenic nonepileptic seizures (PNES) are not mutually exclusive, and up to one-third of epilepsy patients treated at tertiary care epilepsy centers have both disorders [72]. Risk factors for PNES include female sex, comorbid psychiatric disorders (eg, posttraumatic stress disorder, depression, anxiety), a history of physical or sexual abuse, and psychosocial stress. (See "Psychogenic nonepileptic seizures: Etiology, clinical features, and diagnosis", section on 'Common comorbidities'.)

PNES should be considered in patients with previously well-controlled epilepsy who develop recurrent events, particularly when semiology differs from prior seizures, and in patients with apparently drug-resistant epilepsy who have atypical features for seizure by history (eg, asynchronous, variable, or waxing and waning motor activity; prolonged events with incomplete loss of consciousness; events always occurring in front of witnesses). (See "Psychogenic nonepileptic seizures: Etiology, clinical features, and diagnosis", section on 'Clinical manifestations'.)

Video EEG is often required for diagnosis and captures a typical event in a large majority of patients with PNES within the first 48 hours of recording [73,74]. Ongoing neurologic follow-up is an important component of multidisciplinary care for patients with PNES, both because epileptic and nonepileptic seizures frequently co-occur and because mixed or conflicting communication among providers can contribute to the morbidity of the disorder. (See "Psychogenic nonepileptic seizures: Management and prognosis", section on 'Follow-up'.)

COGNITIVE IMPAIRMENT — Cognitive problems are common in people with epilepsy [48]. Cognitive impairment is often present at the time of diagnosis, particularly when assessed by a comprehensive neuropsychologic test battery that can detect mild impairments in multiple domains, and may worsen over time [75-77]. A variety of factors contribute to cognitive dysfunction, including [1,78-83]:

Age

Underlying epilepsy etiology and genetic variants

Effects of frequent or prolonged seizures

Comorbid psychiatric disorders (see 'Screening' above and 'Treatment considerations' above)

Side effects of antiseizure medications and other medications

Complications of other therapies, such as epilepsy surgery (see "Surgical treatment of epilepsy in adults", section on 'Surgical complications')

Any antiseizure medication can impair cognition. In general, the severity can be influenced by titration rate, total daily dose or blood level, and the number of concomitant antiseizure medications. Patients may have variable susceptibility to cognitive side effects depending on their baseline level of function and comorbidities. Among the commonly used antiseizure medications, phenobarbital, benzodiazepines, topiramate, and zonisamide may be the most likely to cause adverse effects. Topiramate can induce specific problems with expressive language (word finding, speech fluency) as well as short-term memory problems, psychomotor slowing, and somnolence. Lamotrigine, gabapentin, and levetiracetam are generally felt to have a low risk of cognitive side effects. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects".)

Although it is commonly accepted that antiseizure medications can impair cognition, patients with epilepsy often have multiple other factors that have adverse cognitive effects. In this context, a prospective study of 331 patients admitted to an inpatient video EEG monitoring unit found that no prescribed antiseizure medication (including topiramate and zonisamide) was independently associated with cognitive dysfunction, suggesting that the risk for medication-induced cognitive changes should not be unduly emphasized [83].

The International League Against Epilepsy (ILAE) neuropsychology task force endorses routine screening of mental health and health-related quality of life in all patients with epilepsy [2,84]. Routine screening can take the form of self-report questionnaires, computerized assessment batteries, and/or clinical questioning of mood, psychologic adjustment, and subjective cognitive complaints (eg, attention, memory, or word-finding difficulties).

Formal neuropsychologic assessment and cognitive rehabilitation, although understudied, may be helpful for some patients with cognitive complaints [48,85]. Small studies support the role of cognitive rehabilitation to improve memory after temporal lobe epilepsy surgery [86,87]. Small studies suggest that methylphenidate is safe in adults with epilepsy and may lead to short-term improvements in memory, attention, and quality of life, even in the absence of premorbid attention deficit hyperactivity disorder [88,89].

SLEEP DISORDERS — Comorbid sleep disorders are common in patients with epilepsy, especially those with medically refractory seizures [90-95]. Comorbid sleep disorders are important to recognize and treat, as sleep disruption may contribute to poor seizure control and decreased quality of life. The three most common disorders are sleep-disordered breathing, restless legs syndrome/Willis-Ekbom disease (RLS/WED), and insomnia [90-94,96].

Obstructive sleep apnea — Obstructive sleep apnea (OSA) is present in approximately 20 to 40 percent of adults with medically refractory epilepsy, and comorbid OSA has been associated with worsened seizure frequency [90-94].

Polysomnography is indicated in patients who report daytime sleepiness or other symptoms of OSA (eg, loud snoring, waking up gasping or choking, witnessed pauses in breathing during sleep). Small studies suggest that screening instruments or home portable oximetry may be useful to better identify OSA in patients who do not report daytime sleepiness or snoring [97]. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults".)

Continuous positive airway pressure (CPAP) therapy is the mainstay of treatment for OSA in adults. Several observational studies in patients with epilepsy and comorbid OSA have found that CPAP use is associated with a reduction in both seizures and interictal epileptiform discharges, as well as improvement in subjective sleepiness, with 50 to 60 percent of patients achieving ≥50 percent reduction in seizure frequency [98-101]. (See "Obstructive sleep apnea: Overview of management in adults".)

Insomnia and other sleep disturbances — Insomnia is reported by more than half of patients with epilepsy and may be more severe among those with comorbid depression and medical illness [102]. Symptoms of RLS/WED may contribute to problems with sleep initiation and should prompt measurement of iron stores and consideration of pharmacologic therapy with either a dopamine agonist or an alpha-2-delta calcium channel ligand. (See "Risk factors, comorbidities, and consequences of insomnia in adults" and "Clinical features and diagnosis of restless legs syndrome and periodic limb movement disorder in adults" and "Management of restless legs syndrome and periodic limb movement disorder in adults".)

CARDIOVASCULAR DISEASE — Adults with epilepsy have increased rates of medical comorbidities that can complicate epilepsy management, contribute to decreased health-related quality of life, increase health care costs, and shorten lifespan [4,103-106]. These associations might result from a variety of factors, including shared risk factors, treatment side effects (eg, weight gain, altered lipid profiles), or shared genetic, environmental, or other factors [103,105].

In an analysis of data from the United States National Health Interview Survey, adults with epilepsy had an increased prevalence of cardiovascular, respiratory, inflammatory, and pain disorders compared with adults without epilepsy [105]. This included increased rates of self-reported heart disease (18 versus 11 percent), high blood pressure (34 versus 29 percent), stroke (14 versus 2 percent), and obesity (34 versus 28 percent). A large database study in Hong Kong found similar results and identified enzyme-inducing antiseizure medications as an independent risk factor for incident physical comorbidities, especially cerebrovascular disease [107]. Observational data suggest that enzyme-inducing antiseizure medications (eg, carbamazepine, phenytoin) may contribute to hyperlipidemia and thereby worsen comorbid cardiovascular disease [108,109].

There is also evidence that most episodes of cardiac arrest in people with epilepsy are not temporally related to a typical seizure [110], distinguishing them from sudden unexpected death in epilepsy (SUDEP), which is thought to occur in the context of a seizure. Several studies have shown that people with epilepsy have a nearly three-fold higher risk of sudden cardiac death compared with the general population, and a 4.5-fold higher risk of sudden cardiac death compared with the risk of SUDEP [111-113]. One explanation for these findings is that chronic epilepsy may trigger repetitive episodes of catecholamine surges, hypoxemia, and myocardial ischemic that cause electrical and mechanical cardiac dysfunction [114]. These data suggest that patients with epilepsy should be monitored with electrocardiography at baseline and during treatment [113].

Recognition of medical comorbidities can facilitate treatment of epilepsy and is particularly important when selecting antiseizure medication therapy. (See "Initial treatment of epilepsy in adults", section on 'Comorbid medical conditions'.)

BONE DISEASE — People with epilepsy are at increased risk for decreased bone mineral density, abnormal vitamin D metabolism, and fractures related to long-term treatment with antiseizure medications. These effects are most commonly associated with antiseizure medications that induce the cytochrome P450 (CYP) enzyme system (eg, phenobarbital, phenytoin, carbamazepine, oxcarbazepine) but have also been described in association with valproate, lamotrigine, and polytherapy. Screening and prevention of bone disease in people with epilepsy is reviewed separately. (See "Antiseizure medications and bone disease", section on 'Screening' and "Antiseizure medications and bone disease", section on 'Treatment and prevention'.)

ACCIDENTS AND INJURIES — Several studies have demonstrated that the risk of seizure-related personal injury, such as falls, bone fractures, drowning, and other accidents, is significantly elevated compared with control subjects [115-121]. However, most of these studies selected preferentially for patients with injuries or more severe seizures, as most subjects were evaluated in emergency departments or tertiary centers [122].

A population-based study in Europe found that seizure-related accidents occurred in only 6.5 percent of the cohort at two years of follow-up; risk was largely determined by higher seizure frequency [123]. Similarly, a subsequent population-based study in the United States found that the risk of seizure-related injury was low and that most injuries were minor and without adverse social or occupational consequences [122]. Seizure frequency was the only significant risk factor for seizure-related injury.

Patients with poorly controlled seizures are at the highest risk for seizure-related injury. However, for most patients with epilepsy, excessive restriction of activities for the purpose of avoiding injury is unnecessary [122]. Supervision of swimming is a reasonable precaution.

The relative risk of a motor vehicle crash in a person with epilepsy compared with other drivers has been variously estimated and may be as high as 2.0. The seizure-free interval (time since last seizure) is believed to be an important factor in assessing the risk of a crash. (See "Driving restrictions for patients with seizures and epilepsy".)

A few studies have suggested that people with epilepsy may be at higher risk of violent assault. In one report, the relative risk of death from homicide in the home was more than twofold higher in patients with epilepsy compared with controls [124]. One population-based study in Canada found that individuals with epilepsy were more likely to suffer assault-related injuries compared with normal controls [43].

It is recommended that clinicians regularly review relevant safety issues with their patients with epilepsy [125].

PREMATURE MORTALITY — People with epilepsy are at substantially increased risk for premature mortality compared with the general population. Across all age groups, standardized mortality ratios (SMRs) range from two to three, indicating that the observed numbers of deaths in people with epilepsy are two- to threefold higher than in reference populations without epilepsy [126-128]. SMRs are substantially higher in children compared with adults and among those with structural/metabolic etiologies, medically refractory epilepsy, and convulsive seizures. In studies that have examined SMRs as a function of time since diagnosis, risk is highest in the first several years after diagnosis and then decreases, although does not normalize, with passage of time [129-131].

Even a single unprovoked seizure (an idiopathic seizure or a seizure that occurs in relation to a preexisting brain lesion or progressive nervous system disorder) is associated with increased mortality. A prospective study, with a mean follow-up of approximately seven years, found a threefold increase in mortality for patients with a first-ever unprovoked seizure (n = 1276) compared with matched controls (n = 2556); the increased mortality was largely related to the underlying cause of the seizures, being independent of seizure recurrence [132].

Comorbid brain disorders contribute to excess mortality, particularly in children. SMRs range from 11 to 50 in patients with disorders characterized as static or progressive encephalopathies; major congenital and acquired central nervous system disorders including cerebral palsy, intellectual disability, and tumors; and degenerative dementias [126]. More modest increases in the SMR (up to 2.1) have been observed in patients with idiopathic or cryptogenic etiologies.

Important causes of death directly attributable to epilepsy include sudden unexpected death in epilepsy (SUDEP), status epilepticus, unintentional injuries, and suicide. Among these, accidental death may be the largest contributor to excess mortality [133]. In observational studies, accidental death rates in people with epilepsy are approximately threefold higher compared with people without epilepsy [133-135]. The risk of a drowning death, in particular, is higher in patients with epilepsy, with an estimated relative risk ranging from 13- to 19-fold [119,134,135].

Psychiatric comorbidity is another important contributing factor. In a population-based cohort study in Sweden, the premature death rate in patients with epilepsy was 9 percent, compared with 0.7 percent in the general population [136]. External causes (eg, accidents, poisonings, suicide, assaults) accounted for 16 percent of epilepsy deaths, approximately half of which were from suicide. Among those who died from external causes, 75 percent had comorbid psychiatric disorders, and comorbid depression and substance misuse were the strongest risk factors for death (adjusted odds ratios 13 and 22, respectively).

In addition to deaths from external causes such as accidents or suicide, deaths attributed to other causes (eg, respiratory disorders, cancer, cerebrovascular disease) may also be higher in patients with chronic epilepsy [107,137-139]. One database study found that patients with epilepsy had high rates of comorbid illness, including pulmonary disease, hypertension, cerebrovascular disease, depression, and alcohol abuse [11]. A comorbidity index score predicted the risk of mortality.

Patients with epilepsy have a small risk of SUDEP [140]. Risk factors for SUDEP include early age of epilepsy onset, frequent generalized tonic-clonic seizures, and intractable epilepsy [140-143]. SUDEP is discussed in detail separately. (See "Sudden unexpected death in epilepsy".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Seizures and epilepsy in adults".)

SUMMARY

People with epilepsy suffer from loss of independence, underemployment, decreased leisure time, decreased physical activity, and increased substance use compared with unaffected adults, all of which can adversely impact quality of life. (See 'Psychosocial issues' above.)

Depression, anxiety, and suicidality are more common in patients with epilepsy than in the general population and should be assessed as part of routine follow-up. Mood-altering side effects of antiseizure medications should not be overlooked as a contributing factor in patients with emergent depression or suicidality. (See 'Depression and anxiety' above.)

Cognitive impairment is often present at the time of diagnosis and may worsen over time. Contributing factors include underlying epilepsy etiology, side effects of medications and other epilepsy therapies, frequent or prolonged seizures, and comorbid mood disorders. (See 'Cognitive impairment' above.)

Sleep disorders, especially obstructive sleep apnea (OSA) and insomnia, are common in people with epilepsy and may contribute to worsened seizure control and quality of life. Polysomnography is indicated in patients who report daytime sleepiness or other symptoms of OSA (eg, loud snoring, waking up gasping or choking, witnessed pauses in breathing during sleep). (See 'Sleep disorders' above.)

Adults with epilepsy have increased rates of medical comorbidities including heart disease, hypertension, stroke, obesity, and metabolic bone disease. (See 'Cardiovascular disease' above and 'Bone disease' above.)

People with epilepsy are at substantially increased risk for premature mortality compared with the general population. Important causes of death directly attributable to epilepsy include sudden unexpected death in epilepsy (SUDEP), status epilepticus, unintentional injuries, and suicide. (See 'Accidents and injuries' above and 'Premature mortality' above.)

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Topic 114559 Version 29.0

References

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