Adverse cognitive effects of antiepileptic pharmacotherapy: Each additional drug matters

Witt, Juri‐Alexander; Elger, Christian E.; Helmstaedter, Christoph

doi:10.1016/j.euroneuro.2015.07.027

Cited by 155 publications

(111 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Most of the patients in our sample were on multiple AEDs. In our sample, cognitive functions tended to be negatively influenced by a higher number of AEDs taken, which is supported by the literature: Each additional AED prescribed resulted in lower performance, especially in executive functions including the Trail Making Test used in our study . In addition, correlation between the level of intellectual functioning and the number of AEDs was reported …”

Section: Discussionsupporting

confidence: 89%

Cognition in epilepsy patients with hypothalamic hamartomas

et al. 2017

View full text Add to dashboard Cite

SUMMARYMany patients with epilepsy caused by hypothalamic hamartomas (HHs) have cognitive impairments during the course of the disease or following neurosurgical treatment. The purpose of this study was to assess cognitive function in these patients, as well as factors influencing preoperative cognitive performance and cognitive outcome after neurosurgical treatment. Using the two largest and most detailed neuropsychology datasets on HH and epilepsy from two centers, we retrospectively report on cognitive functions in 48 patients with structural epilepsy due to HH (mean age AE standard deviation [SD] 20 AE 12 years, range 5-53 years, median 16 years; disease duration mean 17 AE 11 years). Intelligence, verbal learning and recall, and speed and executive functions (processing speed and cognitive flexibility) were assessed before and on average 19 (AE11) months after surgery (interstitial radiosurgery: N = 22; neurosurgical resection/disconnection: N = 26). Prior to neurosurgical treatment, 52% of patients showed impaired executive and 62% showed reduced verbal memory functions. A trend for a detrimental effect of higher drug load on cognitive functioning was found. After neurosurgical treatment, intellectual functions for the entire cohort tended to increase. This correlated with improved seizure frequency and decreased number of antiepileptic drugs (AEDs). However, postoperative outcomes for individual patients were highly variable, with significant deteriorations in 17% (processing speed) to 34% (cognitive flexibility and verbal learning), and performance increases in 17% (intellectual functioning) up to 39% (processing speed) of the patients. Higher levels of presurgical performance were significant predictors of cognitive decline after surgery. These results are highly relevant for patient consultation and may help with therapeutic decisions. KEY WORDS: Neuropsychology, Memory, Iodine seed, Transcallosal resection, Endoscopic resection, Stereotactic radiosurgery.Cognitive abilities and behavior are often impaired in patients with epilepsy due to hypothalamic hamartomas (HHs), but influencing factors have not been adequately understood.1-9 Likelihood for more severe cognitive impairment is predicted by the following: (1) earlier age of first seizure onset, 3 (2) higher seizure frequency, 8 (3) larger HH lesion size, 7 and (4) higher number of antiepileptic drugs (AEDs) at the time of testing. Furthermore, because pharmacotherapy is poorly effective in these patients, neurosurgical approaches have become an option to effectively treat their seizures.

show abstract

Section: Discussionsupporting

confidence: 89%

Cognition in epilepsy patients with hypothalamic hamartomas

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The use of an SCB (+) AED regimen in patients with more severe epilepsy is supported by a small study, which suggested that patients with high seizure frequency before treatment initiation were more likely to achieve seizure freedom with SCB (+) AEDs than levetiracetam. 21 However, in a large study of 809 patients with refractory epilepsy by Canevini et al, 14 incidence of AEs did not differ between monotherapy and polytherapy patients, and did not correlate with AED load. Given these differences in Baseline characteristics, a direct comparison of study outcomes by mechanism of action of the patient's concomitant AED regimen would not be meaningful.…”

Section: Discussionmentioning

confidence: 91%

Changes in drug load during lacosamide combination therapy: A noninterventional, observational study in German and Austrian clinical practice

et al. 2019

View full text Add to dashboard Cite

Introduction Effects of antiepileptic drug (AED) load changes in patients with focal seizures have not been well evaluated. Methods SP1065 (NCT01673282) was a noninterventional, prospective, observational study conducted in a clinical practice setting. Patients (aged ≥18 years) with focal seizures were enrolled within 7 days of being prescribed adjunctive lacosamide. Observation period was ~6 months. Drug load was assessed using percentage change in ratio of actual prescribed dose and World Health Organization defined daily dose (DDD) for concomitant AEDs and all AEDs (including lacosamide). Subgroups were defined for patients with at least one concomitant sodium channel–blocking AED (SCB [+]) and those without (SCB [−]). Results A total of 311 patients were assessed for safety, 302 for measurement of drug load, and 240 for effectiveness. Ratio of AED dose to DDD decreased for concomitant AEDs (−9.6%) and increased for all AEDs (including lacosamide; 15.5%). Median reduction in focal seizure frequency per 28 days was 100% (range: −100, 2275.8). 70.4% and 61.7% of patients had a ≥50% or ≥75% reduction in seizure frequency, respectively; 50.8% became seizure‐free. In the SCB (+) subgroup (n = 149), ratio of AED dose to DDD decreased for concomitant AEDs (−15.0%) and increased for all AEDs (10.7%). In the SCB (−) subgroup (n = 153), ratio of AED dose to DDD decreased for concomitant AEDs (−4.4%) and increased for all AEDs (20.2%). Fifty‐seven patients (18.3%) reported ADRs, most commonly dose >400 mg/d (7.1%). Seventeen patients (5.5%) had ADRs leading to discontinuation. Significance Addition of lacosamide resulted in reduction of concomitant AED drug load regardless of whether concomitant AEDs were SCB (+) or SCB (−). These results indicate that addition of lacosamide in patients with focal seizures could allow clinicians to withdraw or reduce the dose of less well‐tolerated or less effective AEDs.

show abstract

“…additional drug in polytherapy does matter [4,6]. If seizures cannot be fully controlled, two important questions arise: (1) how many AEDs are needed to achieve a significant clinical improvement and (2) whether the same degree of seizure control can be achieved with less AEDs and side effects [13].…”

Section: Strategy Expert Opinion Treatment Decisionsmentioning

confidence: 99%

“…with higher doses and serum levels, and with each additional drug in polytherapy [3][4][5][6]. Another proposed risk factor is the speed of uptitration [7].…”

mentioning

confidence: 99%