Clinical Science

Christian E. Elger , Martin J. Brodie , Henning Anhut , Caroline M. Lee , and Jeannette A. Barrett
Pregabalin is an antiepileptic medication introduced in many countries in 2004–2005 for the treatment of partial epilepsy in adults, when administered in combination with other antiepileptic drugs (AEDs). Clinical trials traditionally employ fixed doses throughout, while in clinical practice, the dose of most AEDs is adjusted gradually, with the dual aim of enhancing tolerability and allowing for optimum effective dosing. The current study included a novel flexible dose regimen in which patients were started on the lowest effective dose of 150 mg/day of pregabalin, followed by a stepwise increase in dose for those patients with inadequate seizure control, up to 600 mg/day. The study goal was to compare the stepwise regimen in terms of both efficacy in seizure reduction and tolerability with a fixed high dose regimen of 600 mg/day. To be eligible for the 12-week study, patients (n = 341) had to be receiving at least one other AED and still experiencing at least four partial seizures in the previous 6 weeks. Both pregabalin regimens were highly effective at reducing the frequency of seizures, with reductions of 35% for flexible dose, and 49% for fixed dose, compared to 11% for placebo. Both regimens were well tolerated, with most side effects being mild or moderate. However, 76% of the patients completed the study in the flexible dose group, versus 58% for the fixed dose group, and more had side effects in the fixed dose group. In conclusion, there appears to be a treatment advantage to adjusting the dose of pregabalin within the therapeutic range of 150–600 mg/day, according to the patient's optimal efficacy and tolerability.