Person:

Moura, Lidia Maria

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 2012-2014, n=20,945) and drew a stratified EHR review sample (n=1,534). 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=2,469) of eligible beneficiaries used at least one anticonvulsant in the 2012-2014 period (4% [n=757] incident users, 8% [n=1,712] 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 (e.g., somnolence). Most ADEs among incident monotherapy users were nervous-system related (68%, n=66/97). Conclusions: 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.

Importance: There is limited evidence concerning optimal seizure prophylaxis after spontaneous intracerebral hemorrhage (sICH). Objective: To evaluate which of four seizure prophylaxis strategies provides the greatest net benefit for sICH patients. Design, Setting, and Participants: Decision model simulating four common scenarios: 1) 60-year-old male with low early- (≤ 7 days post-stroke) (10%) and late-seizure risks (3.6% or 9.8%), and average short- and long-term adverse drug reaction (ADR) risks (9% and 30%, respectively); 2) 80-year-old female with low early- (10%) and late-seizure risks (3.6% or 9.8%), and high short- and long-term ADR risks (24% and 80%); 3) 55-year-old male with high early- (19%) and late-seizure risks (34.8% or 46.2%), and low short- and long-term ADR risks (9% and 30%); and 4) 45-year-old female with high early- (19%) and late-seizure risks (34.8% or 46.2%), and high short- and long-term ADR risks (18% and 60%). Interventions: Four antiseizure drug strategies: 1) Conservative: short-term (7-day) secondary early-seizure prophylaxis with long-term therapy after late-seizure; 2) Moderate: long-term secondary early- or late-seizure prophylaxis; 3) Aggressive: long-term primary prophylaxis; 4) Risk-guided: short-term secondary early-seizure prophylaxis among low-risk patients (2HELPS2B score), short-term primary prophylaxis among higher-risk patients, and long-term late-seizure secondary therapy. Main Outcomes and Measures: Quality-adjusted life years (QALYs). Results: For scenario 1, risk-guided strategy was preferred over conservative, moderate, and aggressive (QALYs = 8.13, 8.08, 8.07, and 7.88, respectively). For scenario 2, conservative and risk-guided strategies performed comparably and were favored over moderate and aggressive (QALYs = 2.18, 2.17, 2.09, 1.15). For scenario 3, aggressive strategy was preferred over moderate, risk-guided and conservative (QALY = 9.21, 8.93, 8.98, 8.77). For scenario 4, risk-guided strategy was preferred over conservative, moderate, and aggressive (QALY = 11.53, 11.23, 10.93, 8.08). Sensitivity analyses suggested that short-term strategies are preferred under most scenarios, and the risk-guided strategy performs comparably or better than alternative strategies in most settings. Conclusions and Relevance: Our model indicates that short-term (7-day) prophylaxis dominates longer-term therapy following sICH. Implementation of the 2HELPS2B score to guide clinical decisions for initiation of short-term primary versus secondary early-seizure prophylaxis should be considered for all patients after sICH.