Higher Adherence to Less Frequently Prescribed Poststroke Antiepileptic

Patients adhered to lamotrigine regimens for poststroke epilepsy (PSE) at higher rates than to more commonly prescribed antiepileptic drugs (AEDs), including the most frequently prescribed carbamazepine, in the largest observational study on AED treatment in PSE to date.

Johan Zelano, MD, PhD, Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden, and colleagues noted that finding high adherence to lamotrigine is in agreement with several other studies on epilepsy in the elderly in which cerebrovascular disease was prominent, despite the fact that carbamazepine, valproate, and levetiracetam are more often prescribed.

"Our findings support the notion of lamotrigine being a well-tolerated AED in PSE, although the slow titration rate required might limit its usefulness in patients with acute seizure situations," Zelano and colleagues indicated.

The investigators conducted the retrospective study with a cohort of over 4000 patients identified in the nation-wide Swedish Stroke Register from 2005-2010, with data on diagnosis and AED drawn from the National Patient Register and Drug Register.

The most commonly prescribed AED was (initially) carbamazepine (n = 2373), followed by valproate (n = 943), levetiracetam (n = 555), lamotrigine (n = 519), and phenytoin (n = 176). During the study period, levetiracetam superseded carbamazepine as most frequently prescribed.

Kaplan Meier analyses applied to determine 5-year retention rates revealed highest adherence for lamotrigine (75%, 95% Confidence Interval [CI] 70.4-79.4), followed by levetiracetam (69%, 95% CI 62.9-75.3), oxcarbazepine (68%, 95% CI 55.2-79.8), valproate (62%, 95% CI 57.8-66.4), carbamazepine (60%, 95% CI 57.6-62.4) and phenytoin (55%, 95% CI 45.2-64.0).

In an analysis of the risk for discontinuing treatment, applying Cox proportional hazard models adjusted for patient characteristics which might influence drug tolerability, lamotrigine and levetiracetam posed significantly lower risks of discontinuation.

"This is in agreement with observations from small RCTs (randomized controlled trials) and indicates lamotrigine or levetiracetam may be good first treatment options in PSE," Zelano and colleagues observed.

The investigators note that while morbidity and mortality following stroke make RCTs vulnerable to selection bias for referral reasons and to avoid low completion rates, their retrospective study across a national population minimized these sources of bias.

In addition to assuming that adherence is a function of drug tolerability, Zelano and colleagues also suggest that the higher risk of discontinuation of phenytoin and carbamazepine could reflect their action of metabolic enzyme induction and propensity for related drug interactions. They note there was a higher prevalence of patients with atrial fibrillation receiving levetiracetam compared to carbamazepine and phenytoin, which suggested that enzyme-inducing AEDs were avoided in patients on anticoagulants.

"Our interpretation is that patients with PSE may be a cardiovascular high-risk group, which should be taken into account when treating PSE," Zelano and colleagues caution. "Among possible measures is choosing non-enzyme-inducing AEDs which do not interfere with stroke prophylaxis or AEDs with low risks of side-effects that may hamper the ability of patients to heed lifestyle choices."

The study, “Retention Rate of First Antiepileptic Drug in Poststroke Epilepsy: A Nationwide Study,” was published in Seizure: European Journal of Epilepsy.