Epilepsy in the Elderly: The Use of Tiagabine

Summary: The incidence of epilepsy increases sharply in patients older than 60 years. There is a clear need for clinical trials designed specifically for this age group, as elderly patients differ from younger patients with epilepsy with respect to seizure etiology, coexisting diseases, concomitant drug therapy, and drug disposition. The new antiepileptic drugs (AEDs) are often associated with fewer side effects than are the traditional AEDs and may be particularly useful in the elderly. The pharmacokinetics of tiagabine (TGB) are not significantly modified in elderly patients, although elimination is more rapid in the presence of enzyme-inducing AEDs. Efficacy and tolerability data on TGB in elderly patients is currently limited, and a formal trial of TGB monotherapy in this age group is needed.     

Epilepsie im Alter

Epilepsies frequently only start in old age and given the current demographic trend the prevalence of epilepsy in the elderly population will increase. This article summarizes the most relevant aspects of diagnosis and therapy in elderly patients with epilepsy. Guidelines, systematic reviews or meta-analyses are lacking and there are only three randomized controlled trials of epilepsy in the elderly. Clinically, seizures in the elderly may be missed since warning signs (auras) and seizure evolution into generalized tonic-clonic seizures are rarer in older people. Sudden loss of consciousness occurs more frequently with increasing age and poses a challenge for the differential diagnosis. Therapy is more complex due to frequent comorbidity and multiple drug therapy necessitating a cautious approach. Therapy is hampered by side effects and drug interactions making a definite diagnosis indispensable and requiring the use of newer generation antiepileptic drugs. In case of doubt, to ensure a safe diagnosis long-term video EEG should be considered even in the elderly before hazarding the negative consequences of a misdiagnosis for years.     

Elderly Patients with Epilepsy: Specific Requirements

Summary: Epilepsy is the third most common neurologic disorder in the elderly and, combined with the progressive aging of the population, this high incidence will lead to an increasing number of elderly patients who require epilepsy care. Treatment of epilepsy in elderly patients is often complicated by the physiologic changes that occur in old age, e.g., reduced absorption, slower metabolism, and deterioration of liver and renal function. Another consideration is that elderly patients are most likely to be suffering from other diseases, necessitating multiple therapies. The potential for drug interactions is therefore high. Because of these factors, traditional antiepileptic drug (AED) therapies are associated with a higher incidence of adverse effects in elderly patients than in younger patients. Tiagabine (TGB) is one of a family of new AEDs recently developed. The newer AEDs tend to have a comparable antiepileptic efficacy and a lower potential for toxicity compared with the traditional AEDs. Clinical studies have shown that age appears to have no effect on the pharmacokinetics of TGB and that there is little difference in the incidence of adverse events between elderly and young patients. Although clinical experience with TGB in the elderly is still limited, TGB shows promise for treatment of epilepsy in the elderly population.     

The choice of antiepileptic drugs in newly diagnosed epilepsy: a national French survey.

The choice of an antiepileptic drug (AED) in patients with epilepsy is mainly based on efficacy and safety of each drug. However, these criteria of drug selection should be further evaluated according to the epileptic syndromes, and adjusted to the sex and age of the patient. Unfortunately, very few studies have been conducted based on these latter criteria. We conducted a survey on the management of epilepsy treatment in adults. This survey was undertaken in France, and led to the establishment of a French consensus on antiepileptic drug treatment in adult patients with newly diagnosed epilepsy. Patients were grouped into 18 categories according to the epileptic syndrome (absence epilepsy, juvenile myoclonic epilepsy, undetermined idiopathic generalized epilepsy, symptomatic or cryptogenic partial epilepsy and unclassified epilepsy), and to the patient's gender and age. Our survey suggests that there is a consensus among French epileptologists for the choice of AEDs, mainly based on the epilepsy syndrome. Gender also plays a crucial role. Sodium valproate and lamotrigine are the two drugs of choice for generalized epilepsies, as well as for undetermined epilepsies. Lamotrigine is often prefered for women of childbearing age. First line AEDs in partial epilepsy are carbamazepine (particularly for men), lamotrigine (particularly for women), and gabapentin (in the elderly). In cases of failure and/or intolerance to one of these AED, the principal alternatives are oxcarbazepine, sodium valproate and topiramate.     

Pharmacological and clinical aspects of antiepileptic drug use in the elderly

In this article, epidemiological and clinical aspects related to the use of antiepileptic drugs (AEDs) in the elderly are highlighted. Studies have shown that people with epilepsy receiving AED treatment show important deficits in physical and social functioning compared with age-matched people without epilepsy. To what extent these deficits can be ascribed to epilepsy per se or to the consequences of AED treatment remains to be clarified. The importance of characterizing the effects of AEDs in an elderly population is highlighted by epidemiological surveys indicating that the prevalence of AED use is increased in elderly people, particularly in those living in nursing homes. Both the pharmacokinetics and the pharmacodynamics of AEDs may be altered in old age, which may contribute to the observation that AEDs are among the drug classes most commonly implicated as causing adverse drug reactions in an aged population. Age alone is one of several contributors to alterations in AED response in the elderly; other factors include physical frailty, co-morbidities, dietary influences, and drug interactions. Individualization of dosage, avoidance of unnecessary polypharmacy, and careful observation of clinical response are essential for an effective and safe utilization of AEDs in an elderly population.     

Epilepsy in the elderly: comparing clinical characteristics with younger patients

The prevalence and incidence of epilepsies in elderly is high. Due to demographic development, the portion of elderly patients with epilepsy will continue to rise over the next decades. In this study, we aimed to investigate seizure semiology, etiology, comorbidity, and therapy in elderly patients dependent on onset of epilepsy and in comparison with younger patients. In a prospective multicentre study, 202 epilepsy patients were included in a consecutive manner and subdivided into three groups (group A1: >65 years, onset of epilepsy after the age of 65 years; group A2: >65 years with early onset epilepsy, seizure onset before the age of 50 years; and group B: <50 years with epilepsy). Clinical data with respect to epilepsy, seizures, comorbidity, etiology, and anti‐epileptic drug (AED) therapy were assessed using a questionnaire developed especially for these patient groups and filled out by the physicians. The clinical profile with regard to etiology, postictal conditions, and comorbidities clearly depends on the age of the patients and age of onset of epilepsy. Patients with an epilepsy onset after 65 years need lower doses of AEDs, gain better seizure control and have more concomitant diseases than younger patients or elderly epilepsy patients with early‐onset epilepsy.     

Prevalence of Epilepsy in the Elderly: The Rotterdam Study

We assessed the prevalence of epilepsy in an elderly population in The Netherlands. The study was conducted from 1991 to 1993 as part of the Rotterdam Study, a population-based door-to-door study of all elderly people living in Ommoord, a suburb of Rotterdam, and included 5,559 persons aged 55–95 years. All subjects were screened for epilepsy through direct questions regarding the existence of epilepsy and antiepileptic drug (AED) use, in addition to relevant questions from the World Health Organization (WHO) protocol for epidemiologic studies of neurologic diseases. Further evaluation of screen positives was made by a panel of 1 study physician and 4 epileptologists, who also classified all confirmed cases of epilepsy according to the classifications of ‘the International League Against Epilepsy (ILAE). The overall prevalence of active epilepsy in our study population was 0.9% including special syndromes and 0.8% excluding special syndromes. The prevalence increased with age from 0.7% for those aged 55–64 years to 1.2% for those aged 85–94 years. The increase with age was detected among men and women both. Our study confirms other findings showing that the prevalence of active epilepsy increases with age in the elderly. The prevalence figures in our study were high as compared with those of other population-based studies. Epilepsy appears to be a major cause of morbidity in the elderly.     

Epilepsy in the elderly

The active prevalence rate of epilepsy among persons over 65 years of age is approximately 1.5%, about twice the rate in younger adults. Treatment of epilepsy in the elderly is complicated by alterations in drug metabolism, use of concomitant medications, and multiple medical problems. Drug interactions are a major issue, and a full knowledge of the isoenzyme profile and protein-binding characteristics of each drug (antiepileptic and other) must be known.     

Epilepsy in the Elderly: Some Clinical and Pharmacotherapeutic Aspects

Summary: The majority of epileptic seizures and epilepsies are no longer manifested in childhood and adolescence; instead their incidence is higher at the age of 65 years or older than during the first two decades of life. After cerebrovascular disorders and dementias, epileptic seizures and epilepsies now constitute the third most frequent neurologic problem encountered in the elderly. Important clinical features of epilepsy in the elderly related to the diagnosis include the most common seizure types and causes. Special features of drug treatment for epilepsy in the elderly result not only from the physiologic changes in the elderly but also from the particular pharmacology of the respective drugs. Because elderly patients very often require other long-term medication in addition to antiepileptic therapy, drug interactions between different antiepileptic drugs and between antiepileptics and other drugs can be of major significance. Other special features of pharmacotherapy for epilepsy in the elderly include the presence of liver and kidney diseases.     

Regional differences and secular trends in the incidence of epilepsy in Finland: a nationwide 23-year registry study

Purpose: Regional variations and temporal trends in the incidence of new‐onset epilepsy are clinically important and may offer clues on how to prevent epilepsy. Methods: We examined regional differences and secular trends in the incidence of new‐onset epilepsy in the Finnish population based on the nationwide full‐refundable antiepileptic drug registry and the population registry in the years 1986–2008. Key Findings: The overall incidence of epilepsy was significantly higher in eastern Finland than in middle [risk ratio (RR) 1.08 (95% confidence interval, CI 1.05–1.12)), p < 0.0001] and western Finland [RR 1.32 (1.30–1.35), p < 0.0001] but it was declining from 1986 to 2008 in all regions [RR 0.83 (0.81–0.84), p < 0.0001]. The mean annual decline was 0.6%. Although the incidence of epilepsy was falling from 1986 to 2008 in childhood [annual decline 1.9%, RR 0.80 (0.75–0.86), p < 0.0001] and in middle age [annual decline 0.8%, RR 0.88 (0.84–0.93), p < 0.0001], it increased significantly in the elderly (age 65 years or older) in all of Finland [annual increase 3.5%, RR 1.25 (1.18–1.33), p < 0.0001], and particularly in east versus west Finland [RR 1.48 (1.42–1.55), p < 0.0001]. As a result, starting with the year 2000, the incidence rate of epilepsy was higher in the elderly than in children for all of Finland. Significance: In view of the falling incidence of epilepsy in childhood and middle‐age in all of Finland from 1986 to 2008, the significant increase in the incidence of epilepsy in the elderly is of concern. The regional increase of epilepsy may offer clues for allocating resources and, possibly, population epileptogenesis between west and east Finland and for strategies to prevent epilepsy in the elderly.     

Epilepsie im Alter

Abstract The elderly are the most rapidly growing section of the population in modern industrialized countries. The incidence of single unprovoked seizures reaches 150–200 at the age of 80 years and the prevalence of active epilepsy in the elderly is around 1–1.5%. Yet, the burden of epilepsy in the very old is not well characterized. Elderly patients often have concomitant neurodegenerative, cerebrovascular, or neoplastic disease, for which they might take multiple drugs. The clinical features of the epileptic seizures and those of syncope in the elderly might differ from younger people, and the EEG might be less sensitive for epileptiform discharges hindering diagnosis. However, seizure semiology is largely unknown and syndrome diagnosis too rarely achieved in this age group. In particular, the frequency of nonepileptic, psychogenic seizures might be underestimated. With advancing age there are drastic changes in drug absorption, disposition, and binding in addition to an increased drug sensitivity hampering antiepileptic treatment. This review examines the epidemiology, clinical appearance, pitfalls of diagnosis, and management of epilepsy in the elderly.      

Epidemiological and medical aspects of epilepsy in the elderly

Both the incidence and prevalence of epilepsy are high among the elderly. Cerebrovascular disease is the most common underlying cause, although as many as 25-40% of new epilepsy cases in the elderly have no obvious underlying etiology. Status epilepticus appears to occur more frequently in individuals greater than 60 years, and the morbidity and mortality of status epilepticus are significantly greater in this age group. Elderly patients with seizures, particularly complex partial seizures, present differently than younger adults, which can lead to misdiagnosis. Post-ictal confusion may last as long as 1-2 weeks in an elderly patient, as opposed to minutes in younger individuals. Adverse events are similar in symptomatology, but are more common in elderly patients and occur at lower doses and plasma drug concentrations. Neuropsychiatric disorders, such as depression and anxiety, are common in elderly patients with epilepsy, although often under-diagnosed and inadequately treated. The risk of osteoporosis is high among elderly women taking antiepileptic drugs, which underscores the importance of assessing bone health and treatment in this group. Management of the older patient with epilepsy requires an understanding of the etiologies and the medical and psychological aspects unique to this age group.     

Epilepsy in the elderly: facts and challenges

The incidence of epilepsy in the elderly has increased steadily over the last few decades. In some industrialized countries, one-third of the population is expected to be over the age of 65 in 2030. Therefore, we will face a dramatic increase in the number of elderly patients with epilepsy, many of whom will likely present comorbidities. This increase will put a heavy burden on health care and pension systems. This article focuses on epidemiology, diagnosis and treatment in epilepsies in the elderlies and outlines current research as well as future requirements for research. The diagnosis of epilepsy in the elderly can be difficult and may require long-term video-EEG monitoring. Stroke is the most frequent etiology in epilepsies in the elderlies. Status epilepticus in acute symptomatic epilepsies often results in fatality and may become an increasing health problem. The article also describes the current strategies in antiepileptic drug treatment and epilepsy surgery in the elderly. Novel antiepileptic drugs are necessary as current antiepileptics have strong interaction potentials and harmful side effects, making them ill-suboptimal for treating epilepsy in the elderly.     

Treatment and management of epilepsy in the elderly demented patient

Epilepsy and seizures are more frequent in the elderly population than in any other age group. The number of individuals older than 65 is constantly increasing, and dementia is a process that predominantly affects this age group. Several studies have shown that dementia is an important risk factor for developing seizures and epilepsy. Seizure semiology in the elderly demented might differ from that of younger age groups and diagnosis can be complicated further by the variety of other causes of transient changes of alertness and behavior that affects these patients. The pharmacokinetic changes of antiepileptic drugs in the elderly make this group a major therapeutic challenge. Side effects and drug interactions play a major role in the choice of antiepileptic agents. This review intends to summarize the existing data to see whether this can help guide the clinician in the treatment and management of epilepsy in the elderly patient with dementia. Nonpharmacologic therapeutic options are also briefly considered.     

Epilepsy in the elderly

The elderly population (Z age 65) continues to grow; this increase extends even to the oldest of the old (Z age 85). This aging population is accompanied by an increase in the cases of epilepsy, which can be especially difficult to diagnose and treat. Age-related difficulties in optimum treatment arise from increased drug sensitivity, altered drug metabolism, comorbid conditions, concomitant multiple medications, inability to self-report symptoms, and drug cost. Although the older antiepileptic drugs (AEDs) are still appropriate treatment for some of the elderly, the newer AEDs should be considered because of their different efficacy and safety profiles.     

Drug absorption in the elderly: biopharmaceutical considerations for the antiepileptic drugs

The management of antiepileptic drug (AED) pharmacokinetics remains a challenge in the treatment of patients with epilepsy. Drug characteristics, such as protein binding, mechanisms of drug elimination, and the potential for pharmacokinetic/pharmacodynamic interactions, are important considerations for drug selection and may help determine overall effectiveness. In elderly patients with epilepsy, the likelihood of polytherapy, along with physiological changes associated with aging, can make pharmacokinetic issues even more significant. One aspect of pharmacokinetics that has received less attention is the process of oral drug absorption. Aging can have variable effects on the gastrointestinal system. Some of these physiological changes have the potential to impact absorption patterns of some medications, including AEDs. Altered oral protective reflexes, xerostomia, and delayed esophageal emptying in elderly patients may complicate oral administration of some medications. Altered gastric pH could modify drug absorption, and modified gastric emptying rates can influence the bioavailability of some AEDs. Finally, intestinal transit times may be slower in elderly patients compared to younger patients, possibly altering the absorption of some AEDs. These age-related physiological changes that may affect AED pharmacokinetics should be considered when treating elderly patients with epilepsy.     

Practical strategies for switching to newer antiepileptic drugs

Traditional antiepileptic drugs (AEDs) are associated with drug interactions and side effects that limit their safety and tolerability. Side effects of traditional AEDs are especially problematic for children and adolescents, women of childbearing age, and the elderly. Many patients with epilepsy may benefit from switching from a traditional AED to a newer agent because the newer agents are generally better tolerated and are less likely to cause drug interactions. Clinical studies have demonstrated improved therapeutic efficiency with better tolerability in patients switching from a traditional AED to lamotrigine, oxcarbazepine, or topiramate monotherapy or combination therapy.     

Epilepsy in the elderly

There are many unique characteristics in elderly patients with epilepsy. The incidence of seizure in this age group is the highest of any age group and continues to increase as people live longer. Etiology of seizures is different than for adults and includes cerebrovascular disease, dementia, closed head injury, and metabolic encephalopathies. The elderly patient with epilepsy most often presents with complex partial seizures that have a higher recurrence rate than the younger population. The seizures are often difficult to diagnose since they present with atypical symptoms, particularly prolonged postictal symptoms, including memory lapses, confusion, altered mental status, and inattention. There are also therapeutic challenges due to age-related changes in pharmacokinetics, including variations in absorption, distribution, metabolism, and excretion. These must be considered when selecting antiepileptic drug (AED) therapy to avoid harmful side effects. In addition, several of the AEDs have drug-drug interactions, a problem potentially exacerbated in this population of patients due to the use of medications for comorbid conditions.     

Epilepsie im höheren Lebensalter

The percentage of elderly people in Germany and the number of patients with late-onset epilepsy will increase in the coming years. However, there are only a few studies that focus on quality of life (QoL) in this patient group. This article summarizes the literature selected via a PubMed search. The listed studies show differences in the definition of epilepsy in the elderly (age of manifestation >?60 or 65 years) and in the distinction between long-term epilepsy (LTE) in the elderly (starting <?60 or 65 years) and new-onset epilepsy (NOE) in the elderly (>?60 or 65 years). Nevertheless, the studies present similar results. Elderly patients with epilepsy did not necessarily experience more restrictions due to epilepsy than younger adults did, but they had greater anxiety regarding injuries and accidents, e.g., fractures, compared with younger patients. Younger adults reported more restrictions with respect to employment and family, but experienced a higher overall QoL and had more social and leisure activities. Patients with LTE showed no differences in epilepsy-related restrictions or QoL compared with NOE patients; however, patients with LTE had worse seizure control and more adverse effects of anticonvulsant therapy, but less comorbidity and dependence on help than people with LTE did. Other factors such as age and age at onset of epilepsy had no or only subordinate influence on epilepsy-related impairments. In one study, people with LTE reported fears of stigmatization more often than patients with NOE did. In view of the limited number of studies on QoL in elderly epilepsy patients, further research is needed especially in very old people.     

Epilepsy: comorbidity in the elderly

Elderly people experience the highest incidence of epilepsy and their clinical mananagement is often challenging, due to a potential increase in the likelihood of adverse treatment events. In addition, concomitant diseases are highly prevalent in this population and elderly patients are likely to be prescribed a number of medications that must be taken concurrently. As a result, the incidence of adverse drug–drug interactions and adverse drug reactions is also extremely high. Thus, the treatment of elderly patients with epilepsy requires careful consideration of any comorbid conditions and concomitant medications. Most adverse events are drug-related and are therefore preventable. It is important to consider these complications when prescribing antiepileptic drug (AED) treatment. An AED with broad-spectrum efficacy, good tolerability and a favourable drug interaction profile (e.g. valproate, gabapentin and lamotrigine) may prevent many unwanted drug interactions and side effects.