New Research Highlights Reasons, Risk Factors, and Consequences for Self-Discontinuation of Antiseizure Medication in Newly Diagnosed Epilepsy

In total, 65% of those who self-discontinued treatment experienced further seizure recurrence, which led to a majority (84%) of patients restarting treatment.

In a cohort of nearly 500 patients with newly diagnosed and treated epilepsy, new data showed that self-discontinuation of treatment with antiseizure medications (ASMs) is common, with nearly one-sixth of the sample choosing to terminate their treatment regimen. The decision to discontinue was mainly influenced by the ASM adverse effects (AEs) and the success of the therapy.1

In total, 78 of the 489-patient cohort (14%) self-discontinued ASM therapy after a median treatment duration of 1.4 years (interquartile range [IQR], 0.4-2.9) and after a median duration of seizure freedom of 11.8 months (IQR, 4.6-31.8). The most common reasons were experience of AEs (n = 32; 41%) and belief that treatment was no longer required (n = 27; 35%). The remaining 9 patients discontinued treatment due to planning or entering pregnancy.

Senior author Patrick Kwan, MD, professor of neurology, Monash University, and colleagues analyzed self-discontinuation of ASM in recently diagnosed patients through a review of clinic letters and hospital correspondence. Most of the cohort (62%) were male and most (63.6%) had focal epilepsy. In total, 140 (28.6%) individuals had epileptiform abnormalities on EEG and 228 (46.6%) had epileptogenic lesions on neuroimaging at baseline.

Among those who self-discontinued, 81% (n = 63) discontinued the first prescribed ASM, 17% (n = 13) discontinued the second ASM regimen, and 3% (n = 2) discontinued the third trialed ASM regimen. Valproate (38%) represented the most discontinued monotherapy, followed by carbamazepine (21%), and phenytoin (14%), among others. Notably, 49% (n = 38) of patients who self-discontinued had been seizure free for at least 1 year prior to making that decision.

On a multivariable analysis, patients with epileptogenic neuroimaging lesions were less likely to discontinue therapy (HR, 0.44; 95% CI, 0.23-0.83), as were patients who presented with seizure clusters (HR, 0.32; 95% CI, 0.14-0.69) and those with tonic-clonic seizures as part of their seizure semiology (HR, 0.36; 95% CI, 0.66-0.86). Additionally, those who were sleep deprived prior to having seizures were associated with a higher rate of treatment discontinuation (HR, 1.80; 95% CI, 1.05-3.09), as was significant alcohol or illicit drug use (HR, 2.35; 95% CI, 1.20-4.59).

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"The frequency and consequences of self-discontinuation of ASM treatment is under-explored, including in randomized studies of treatment, and requires further detailed evaluation to guide real-world application of evidence in the management of patients with newly diagnosed epilepsy," Kwan et al wrote. "Reasons for discontinuation highlight areas for improved discussion with patients during the early course of their condition, including the chronicity of epilepsy and pre-emptive management strategies for current or potential adverse effects."

After self-discontinuation of therapy, 65% of patients experienced further seizures, including a high proportion (84%) of those who discontinued due to AEs. In contrast, less than half (48%) of patients who discontinued due to the belief that ASMs were no longer required had further seizures (Fisher exact test, P = .005). Notably, half of the 28 patients who had been seizure free for at least 2 years prior to self-discontinuation had seizure recurrence.

Seizure-related injury was documented in 28% (n = 22) of those who self-discontinued and were no longer on ASM. Orolingual trauma, occurring in 12 individuals, was the most common injury reported. During the follow-up period, 4 patients who were off ASM treatment were involved in seizure-related motor vehicle accidents while driving, without major injury. Fifteen of the 22 (68%) patients who had any documented seizure-related injury restarted therapy.

In total, 55% (n = 43) of patients who self-discontinued eventually restarted their ASMs, most of which (n = 41) were done following seizure recurrence. Despite recurrent seizures, 10 participants decided to not restart their treatment regimen. Of patients who restarted ASMs, 7 again subsequently discontinued treatment.

REFERENCE
1. Sharma S, Chen Z, Rychkova M, et al. Risk factors and consequences of self-discontinuation of treatment by patients with newly diagnosed epilepsy. Epileps & Behav. Published online April 25, 2022. doi:10.1016/j.yebeh.2022.108664