NEW YORK (Reuters Health) – Adding pregabalin (Lyrica) to existing therapy for poorly controlled partial seizures reduces seizure frequency and is generally well tolerated over the long term, according to pooled data from six open-label extension studies.

The U.S. Food and Drug Administration approved pregabalin as adjunctive treatment for partial onset seizures in adults in 2005. Several trials have shown it to be effective and safe in the short term. But such drugs are usually taken for years, and so knowledge of long-term effects is crucial, the investigators note.

In a study reported online March 19th in Epilepsia, Dr. Basim M. Uthman from Weill Cornell Medical College in Doha, Qatar, and colleagues analyzed data on 2061 patients with partial onset seizures with or without secondary generalization. The original studies had ranged in duration from 3.5 to 8 years; the average duration of pregabalin treatment in the open-label extension phases was 1.5 years. The cohort was exposed for a total of 3877 person-years.

Pregabalin doses ranged from 75 to 600 mg/day administered two or three times daily along with one or more other anti-epileptic drugs. Treatment reduced mean seizure frequency by 30% to 50%, and 43% of patients had reductions of more than 50%, according to the article.

Twelve percent of all patients had a 6-month seizure-free period, and 6% were seizure free for the most recent year.

During follow-up, about a third of patients stopped taking the drug due to lack of efficacy. In these patients, the average pregabalin dose was around 300 mg/day, whereas it was roughly 500 mg/day in patients who continued with treatment. It’s possible “that those who discontinued due to lack of efficacy may not have received a sufficient dose and that tolerability may have been a limiting factor for dose escalation,” the researchers say.

Side effects of dizziness and somnolence, though common, tended to resolve within several weeks, Dr. Uthman’s team notes. Similarly, weight gain associated with treatment generally stopped after the first 6 months.

Serious treatment-related adverse events occurred in 21 patients, but none resulted in death.

There were four cases of status epilepticus — “well within the expected range,” according to the authors – and four cases of sudden unexpected death in epilepsy, also within the expected range.

The authors find it “encouraging” that no patient developed aplastic anemia, liver failure, or Stevens-Johnson syndrome. Furthermore, treatment did not appear to be associated with an increased risk of cancer.

“Overall, add-on pregabalin was well tolerated…over several years of treatment and no new safety concerns were identified,” the authors conclude.

These studies were sponsored by Pfizer Inc.

Reference:
Epilepsia 2010.