Seizure Control Diminishes With Subsequent Antiepileptic Drug Therapy

Patients with tough-to-treat seizures may require nonpharmacologic treatment such as resective surgery.

The majority of patients with epilepsy achieve seizure control with their first antiepileptic drug (AED), and the likelihood of control decreases with additional AEDs, according to findings from an observational, longitudinal cohort study published in JAMA Neurology.

In this study, investigators evaluated outcomes of patients with epilepsy who were newly treated with AEDs at the Epilepsy Unit of the Western Infirmary in Glasgow, Scotland (n=1795). Patients who experienced ≥2 seizures were managed with an AED. Investigators assessed outcomes at 4-month increments and continued to follow patients’ progress for 2 years or until death.

At the time of the study’s end, 63.7% (n=1144) of patients treated with AEDs were seizure free for ≥1 year. The majority of those who were seizure free had been treated with only 1 AED (86.8%) or had control of seizures with either the first or second AED (89.9%).

The second and third AEDs provided an 11.6% and 4.4% chance for achieving freedom from seizures if the initial AED failed to produce an effect. Seizure control was achieved in only 2.12% of patients with additional AED support. In addition, there was a significantly greater chance for treatment response failure with additional AEDs in difficult-to-control cases of epilepsy (odds ratio 1.73; 95% CI, 1.56-1.91; P <.001).

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According to the investigators, there was potential selection bias in this population because participants were from a single center in Glasgow. The small number of participants in each AED subgroup may have also limited the analyses’ statistical power.

Among patients with drug-resistant epilepsy, clinicians should consider early “nonpharmacological therapies, such as resective surgery and brain stimulation techniques,” suggested the investigators.


Chen Z, Brodie MJ, Liew D, Kwan P. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: A 30-year longitudinal cohort study [published online December 26, 2017]. JAMA Neurol. doi: 10.1001/jamaneurol.2017.3949