NEW YORK (Reuters Health) – A comparison of 10 seizure drugs in older epilepsy patients shows that lamotrigine is the most effective — based on 12-month retention and freedom from seizures — while oxcarbazepine was the least effective.

Lamotrigine was followed closely by levetiracetam, the researchers said.

Many factors can complicate the management of seizures in older people, such as other illnesses, drug interactions, and aging-related changes in pharmacokinetics and pharmacodynamics, according to senior author Dr. Lawrence J. Hirsch and colleagues at Columbia University in New York.

But the newer antiepileptic drugs may offer fewer adverse effects and lower potential for interactions with other medications, they note in the April issue of Archives of Neurology.

To compare the tolerability and effectiveness of the most commonly used antiepileptic drugs, the investigators reviewed 12-month retention and seizure-free rates in 417 outpatients with epilepsy. All were 55 and older, and all had begun taking one of the 10 most commonly prescribed antiepileptic drugs between 2000 and 2005.

In alphabetical order, these were carbamazepine, clobazam, gabapentin, levetiracetam, lamotrigine, oxcarbazepine, phenytoin, topiramate, valproate sodium, and zonisamide.

Before adjustment for illness severity, lamotrigine showed the highest 12-month retention rate, at 78.8% (in 85 patients), significantly higher than for carbamazepine (31 patients, 48.4%), gabapentin (39, 59%), oxcarbazepine (34, 23.5%), phenytoin (27, 59.3%), and topiramate (18, 55.6%).

Levetiracetam had the second highest retention rate, of 72.5% for 102 patients, significantly higher than for carbamazepine and oxcarbazepine.

When the researchers looked separately at refractory disease, retention rates in 250 patient-drug combinations were similar, but the only significant difference was for oxcarbazepine (24 patients, 12.5% retention rate) compared to all other medications.

The proportion of patients who had 12 months free of seizures was highest with lamotrigine, at 54.1% for 85 patients, before controlling for severity. Levetiracetam was second best, at 42.6% for 48 patients. All other medications had 12-month seizure freedom rates below 40%.

For this outcome too, patients with refractory disease had the highest rates with lamotrigine (47.4% for 38 patients) and levetiracetam (38.9% in 54 patients). Oxcarbazepine had the lowest seizure freedom rate in the refractory group, at 4.3% for 23 patients.

Adverse effects led to drug discontinuation in 29.1% of patients, with the most common being imbalance, drowsiness, gastrointestinal disturbance, dizziness, cognitive adverse effects, allergies, and psychiatric adverse effects. Patterns of adverse effects varied among the drugs; for example, the most common side effects with levetiracetam were drowsiness and psychiatric events, while for topiramate, cognitive effects and drowsiness were most common.

“This study underscores the need for further prospective trials for evaluating safety and effectiveness of multiple anti-epileptic drugs in older adults, a cohort that has been consistently underrepresented in prior studies, and suggests that lamotrigine and levetiracetam should be included in any future trials of treatment of epilepsy in older adults,” Dr. Hirsch and his colleagues conclude.

Reference:

Arch Neurol 2010;67:408-415.