Treatment patterns, strategies, and preferences after first anti‐seizure medication failure in focal epilepsy: Findings from the
SANAD
and
SANAD II
Isaac J. Egesa, Anthony G. Marson, Laura J. Bonnett, Richard Emsley, Catrin Tudur Smith Abstract
Objective
To describe treatment decisions after first anti‐seizure medication (ASM) failure in focal epilepsy and describe how they have changed across two trial eras, and whether observed prescribing matched clinicians stated preferences.
Methods
We analyzed the focal epilepsy cohorts from two UK pragmatic, randomized trials, Standard and New Antiepileptic Drugs (SANAD) (1999–2006) and SANAD II (2012–2019). Only initial ASM allocation was randomized; subsequent decisions reflected usual care, with medication changes and reason recorded prospectively. We reconstructed treatment sequences, classified first decisions after failure as switch or add‐on, and stratified by reason, and compared prescribing with cross‐sectional survey of UK epilepsy specialists.
Results
Of those enrolled, 1644 of 1721 (95.5%) in SANAD and 933 of 990 (94.2%) in SANAD II were included. First‐line ASM failed in 798 (48.5%) and 360 (38.6%), respectively. Among classifiable failures from inadequate seizure control (ISC), add‐on was 40.9% (79/193) in SANAD and 63.1% (82/130) in SANAD II. After lamotrigine failure, the only randomized ASM in both trials, add‐on was 44.4% (16/36) in SANAD to 74.3% (26/35) in SANAD II. Forty‐six specialists completed the survey. Their preferred next ASM broadly matched SANAD II prescribing: after lamotrigine failure from ISC, 74% (31/42) chose levetiracetam, prescribed to 66% (23/35); after levetiracetam failure, 51% (21/41) chose lamotrigine, prescribed to 52% (26/50). Strategy preferences differed: respondents favored switching after each specified failure, yet add‐on predominated after ISC in SANAD II.
Significance
Add‐on treatment after first ASM failure from ISC was more common in the later trial. Clinician‐preferred next ASMs were consistent with observed practice, but preferred strategy did not. Neither trial was designed to compare these strategies, and cohorts differed in baseline characteristics and completeness of recorded reason for failure. Randomized evidence is needed to determine whether switching or add‐on yields better seizure control, tolerability, and treatment‐retention outcomes.