Patterns of anticonvulsant use and adverse drug events in older adults

Abstract

Purpose To examine indications for, duration of use, and rate of adverse drug events (ADE) attributable to anticonvulsant initiation, as adjudicated by expert review of electronic health records (EHR) of older adults. Methods We identified a cohort of community dwelling Medicare beneficiaries with linked EHR (aged 65+, continuously enrolled with a large health system/until death between 2012 and 2014, n = 20 945) and drew a stratified EHR review sample (n = 1534). An expert reviewed all records to adjudicate anticonvulsant use, years of use, indication for use, and evidence of ADEs attributable to anticonvulsant initiation. After excluding patients with insufficient EHR data (n = 37; 2%), we reconstructed the cohort using inverse probability weights to resemble the original cohort of eligible beneficiaries (n = 20 380). Among incident users of a single anticonvulsant, we estimated the rate of ADEs and described the type and severity of ADEs. Results Overall, 12% (n = 2469) of eligible beneficiaries used at least one anticonvulsant in the 2012 to 2014 period (4% [n = 757] incident users, 8% [n = 1712] prevalent users). Incident users were most frequently prescribed gabapentin (n = 461/757, 61%), benzodiazepines (n = 122/757, 16%), and levetiracetam (n = 74/757, 10%); the most common indication was pain relief (n = 214; 28%) followed by epilepsy (n = 53; 7%). Among incident users, the overall ADE rate was 10/100 person‐years (95% CI 4‐20/100 person‐years), of which 29% (n = 28/97) were life threatening (eg, somnolence). Most ADEs among incident monotherapy users were nervous system related (68%, n = 66/97). Conclusion Many older adult community dwelling traditional Medicare beneficiaries had clinically significant ADEs likely attributable to the initiation of anticonvulsant therapy, which was begun for a range of indications.

Comparative Effectiveness and Safety of Seizure Prophylaxis Among Adults After Acute Ischemic Stroke

“…14,46 Seizures and seizure-like events are considered AIS symptoms (ie, symptomatic seizures), and prophylaxis may be unnecessary unless they recur after the acute AIS recovery period is over (ie, post-AIS epilepsy, by definition). 11,47,48 The most examined ASDs have been levetiracetam, 37,39,40 valproic acid, 38 and sodium valproate, 41 with an urgent need to evaluate the safety and effectiveness of newer drugs such as lacosamide, carbamate, brivaracetam, vigabatrin, and eslicarbazepine. 49 Evidence shows the side effects of levetiracetam are as follows: behavioral disturbances (eg, anxiety, anger, and depression), nausea/vomiting, infections, somnolence, and fatigue that may precipitate fall-related injuries.…”

“…Our mortality results represent the lower bounds of exposure patterns and outcome effects than other practice patterns. 56 This is partly because this study took place in a certified Advanced Comprehensive Stroke Center that aims to treat patients with AIS with the highest quality of care. Lastly, even though we were able to obtain accurate death dates, examining the cause of death for each patient was out of scope for this study.…”

“…14,46 Seizures and seizure-like events are considered AIS symptoms (ie, symptomatic seizures), and prophylaxis may be unnecessary unless they recur after the acute AIS recovery period is over (ie, post-AIS epilepsy, by definition). 11,47,48…”

“…4,10 Despite the increasing concerns of the prevalence of use, there remains limited real-world information about the effectiveness and safety of seizure prophylaxis among older adults in the United States. [11][12][13] ASDs may lead to life-threatening adverse effects (eg, falls, infections, and somnolence). 14,15 Older adults on polytherapy are more sensitive to drug toxicity, 16,17 as are those with acute brain insults such as AIS.…”