Levetiracetam monotherapy--outcomes from an epilepsy clinic

Levetiracetam (LEV) is a broad spectrum antiepileptic drug (AED) with a unique mechanism of action. This retrospective audit explores outcomes in patients commenced on LEV monotherapy at the Epilepsy Unit at the Western Infirmary, Glasgow, Scotland from 1st January 2001 until 30th June 2009.

LEV monotherapy was started in 228 patients (89 men, 139 women, aged 12-81 years [median 28 years]). Of these, 161 (70.6%) had partial-onset seizures, 59 (25.9%) had idiopathic generalized epilepsies (35 primary generalized tonic-clonic seizures [PGTCS], 20 juvenile myoclonic epilepsy, 4 juvenile absence epilepsy), and 8 (3.5%) had unclassified GTCS. Initial dosing was 250 mg twice daily for 2 weeks, followed by 500 mg twice daily. Patients were reviewed every 6-8 weeks. If required, the LEV dose was titrated in 500 mg increments to a maximum tolerated or effective dose.

In total, 112 (49.1%) patients remained seizure-free for ≥1 year on a median LEV dose of 1000 mg/day (range 500-3000 mg/day). Patients were more likely to achieve seizure freedom with LEV as a first monotherapy (81 of 149 [54.4%]), as opposed to switching from another AED (31 of 79 [39.2%]; p=0.03). In this latter group, seizure freedom was more likely in those who switched after failing their 1st or 2nd AED (n=39 of 64 [60.9%]), compared to later in the treatment schedule (n=2 of 15 [13.3%]; p=0.029). Patients reporting <5 seizures (70 of 118) prior to starting LEV were more likely to become seizure-free than those with ≥5 seizures (42 of 110; p=0.001). Thirty-six (15.8%) patients had a ≥50% seizure reduction over 1 year; 43 (18.9%) were classified as having a <50% improvement, but elected to continue on LEV. The drug was withdrawn in 37 (16.2%) patients (30 side effects, 7 lack of efficacy). Eighteen (7.9%) patients reported intolerable neuropsychiatric symptoms (7 aggression, 7 mood swings, 2 irritability, 2 depression). Other side effects leading to drug withdrawal included sedation (n=5) and lethargy (n=4).

Seizure freedom was achieved in around half the patients on a median LEV dose of 1000 mg/day. This was more likely to occur in those taking the drug as first monotherapy, and in those with <5 pre-treatment seizures. Around 50% of those who discontinued LEV due to side effects developed neuropsychiatric symptoms.