Effect of cotherapy reduction on tolerability of epilepsy add-on therapy: a randomized controlled trial

Adverse effects are the most common cause for failure of an antiepileptic drug (AED), especially when an AED is added to existing therapy. With the increased drug load, it may not be possible to titrate the newly added AED to effective doses. Reducing the dosage of AED cotherapy as the new drug is introduced may improve tolerability.

To evaluate reduction of AED cotherapy as a strategy to improve tolerability and patient retention when a new AED is added to existing therapy.

In a 20-week, randomized, open-label study, topiramate was initiated as add-on therapy in adults and adolescents (> or =12 y of age) with inadequately controlled partial-onset seizures. Patients were randomized to receive treatment in which adverse events could be managed by adjustments in AED cotherapy (flex-dose group) or treatment in which AED cotherapy dosages remained fixed (fixed-dose group). Topiramate could be adjusted as needed in both groups. In the flex-dose group, patients exited randomized treatment when topiramate was discontinued. In the fixed-dose group, patients exited when AED cotherapy was reduced due to adverse events or when topiramate was discontinued. The primary study outcome was the percentage of patients exiting randomized treatment due to adverse events.

The flex-dose group comprised 297 patients; 302 patients were in the fixed-dose group. Significantly fewer patients in the flex-dose group exited the study due to adverse events (16% vs 23% in the fixed-dose group; p = 0.02). In the flex-dose group, 10% (17 of 168) of patients discontinued topiramate due to adverse events after AED cotherapy was reduced versus 22% (29 of 129) when AED cotherapy was not reduced.

Reduction of AED cotherapy is a useful strategy to improve tolerability and retention when topiramate is initiated as adjunctive therapy.