Pharmacological and clinical aspects of antiepileptic drug use in the elderly

Perucca, Emilio; Berlowitz, Dan R.; Birnbaum, Angela K.; Cloyd, James C.; Garrard, Judith; Hanlon, Joseph T.; Pugh, Mary Jo

doi:10.1016/j.eplepsyres.2005.07.017

Cited by 123 publications

(87 citation statements)

References 64 publications

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“…tients with traumatic brain injury fared considerably worse (35% remission) (Mohanraj and Brodie, 2005b). Irrespective of etiology, age per se may affect responsiveness to AEDs as a result of alterations in pharmacokinetics (Perucca, 2006;Perucca et al, 2006) and pharmacodynamic sensitivity (Ramsay et al, 1994;Kramer, 1999;Tallis et al, 2002). In particular, elderly patients tend to achieve seizure control at lower AED dosages and lower serum AED levels than younger subjects, but they are also more susceptible to central nervous system (CNS) side effects such as impairment of gait, as well as action and postural tremor (Ramsay et al, 1994;Kramer, 1999).…”

Section: Discussionmentioning

confidence: 99%

An International Multicenter Randomized Double‐Blind Controlled Trial of Lamotrigine and Sustained‐Release Carbamazepine in the Treatment of Newly Diagnosed Epilepsy in the Elderly

et al. 2007

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Summary:Purpose: To assess the comparative effectiveness, efficacy, and tolerability of lamotrigine (LTG) and sustainedrelease carbamazepine (CBZ) in the treatment of newly diagnosed epilepsy in the elderly.Methods: Patients aged 65 years or older, who had experienced at least two unprovoked partial and/or generalized tonicclonic seizures, were randomized to receive LTG (n = 93) or CBZ (n = 92) according to a multicenter double-blind, parallelgroup design. Trial duration was 40 weeks and included a 4-week dose escalation followed by a maintenance phase during which dosages could be adjusted according to response. Initial, maintenance and maximum dosages were 25 mg, 100 mg, and 500 mg per day for LTG, and 100 mg, 400 mg, and 2,000 mg per day for CBZ, respectively. The primary end point was retention in the trial. Results:In the LTG group, 68 patients (73%) completed the 40-week study period compared with 61 (67%) in the CBZ group, a nonsignificant difference. Time to withdrawal from any cause did not differ between groups (p = 0.34). The number of subjects who completed the 40-week period and were seizure free in the last 20 weeks was 48 (52%) in the LTG group and 52 (57%) in the CBZ group. Adverse events leading to withdrawal occurred in 13 (14%) subjects in the LTG group and 23 (25%) subjects in the CBZ group.Conclusion: LTG and CBZ showed comparable effectiveness, with a trend for higher seizure-free rates for CBZ and better tolerability for LTG. Differences in outcome compared with previous trials may be related to different dosing rates and use of a sustained-release formulation for CBZ.

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Section: Discussionmentioning

confidence: 99%

An International Multicenter Randomized Double‐Blind Controlled Trial of Lamotrigine and Sustained‐Release Carbamazepine in the Treatment of Newly Diagnosed Epilepsy in the Elderly

et al. 2007

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“…Fortunately, trials addressing pharmacokinetics are often done separately in this population. The elderly tend to have slower elimination of drugs (by 20-40%) owing to several factors, including slowed metabolic rate and reduction in renal clearance (24). Thus, the common wisdom of "start low and go slow" would be particularly prudent in this group.…”

Section: Issues Related To Change In the Body Over Timementioning

confidence: 99%

AED Treatment through Different Ages: As Our Brains Change, Should Our Drug Choices Also?

French

Staley

2012

Epilepsy Curr

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The management of epilepsy can be difficult owing to the inherently complex nature of the disorder. Pharmacotherapy with antiepileptic drugs (AEDs) is the most common treatment approach. Thirteen new AEDs have been approved by the FDA since 1993. The increase in available drugs provides more options for the prescribing physician, but it has also increased the complexity of drug selection. Determining which of the many AEDs is the best "fit" for a patient can be a challenge. It is increasingly taught that AED selection can be "personalized, " based on patient characteristics such as age, gender, and the presence of comorbidities. These patient characteristics may be related to the efficacy, safety, and tolerability of AEDs and can help determine the most appropriate drug therapy for an individual.In this review, we focus on age as a factor in selecting the most appropriate AED. There are a number of reasons why age may be a factor in AED selection. Most physicians are aware that many seizure types and syndromes have specific ages of onset, and because many AEDs are more effective for subsets of seizure types and syndromes, some drugs will be more appropriate for individuals of certain ages. For example, ethosuximide, is a drug used to treat absence seizures, a seizure type found most commonly in children and adolescents. This issue will not be discussed further, as it relates more to drug selection based on seizure type. But there may also be other issues that make some drugs more or less appropriate or useful at different ages, even if the seizure type and syndrome are the same. It is these issues that will be discussed in the current review. Examples include changes in brain function at different ages, changes in underlying epilepsy etiology, changes in pharmacokinetics, and changes in frequency and types of adverse effects. There is a great need for data regarding AED efficacy relative to age from randomized control trials (RCTs) to guide clinical decision-making, but these types of studies are few. Until those studies are completed, clinicians may give consideration to patient age when determining a treatment plan for epilepsy, but there will be a paucity of scientifically rigorous data to guide them. Differences in Underlying Brain FunctionHow does the brain differ at different ages, and how can those differences impact drug selection? In newborn infants, seizures are different that those seen at later ages, both semiologically and possibly in regards to underlying pathophysiology and development of neurotransmission. Seizures can present as focal or migrating and multifocal (1) and may be subtle and fragmented. The circuitry in the immature brain is different. The infant brain shows an overdevelopment of excitatory neurotransmission, and a relative underdevelopment of inhibitory transmission. Moreover, even the traditional neurotransmitter GABA may behave differently in the neonatal brain, activating excitatory rather than inhibitory pathways (2). Clearly, these and other differences related to brain matura...

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“…Cognitive alterations, hyperactivity and other conduct disorders are frequently observed in children treated with phenobarbital, although these symptoms may also occur in association with phenytoin, benzodiazepines, gabapentin and vigabatrin [11]. Fragile elderly patients, often with several co-morbidities and treated with many drugs, are also at special risk for development of cognitive and motor adverse effects induced by several AEDs [41].…”

Section: Analysis Of Risk Factorsmentioning

confidence: 99%