Rapid onset of seizure suppression with pregabalin adjunctive treatment in patients with partial seizures

Abstract

SUMMARYPurpose: To determine the time at which pregabalin demonstrates seizure-suppressing activity when given as adjunctive treatment to patients with refractory partial seizures. Methods: Data from four similar 12-week, randomized, double-blind, placebo-controlled, parallel-group trials in patients with refractory partial seizures were pooled to provide an adequate sample to compare the proportion of patients free of seizures on each study day between pregabalin (combined 150-600 mg/day groups) and placebo (combined groups). A generalized estimating equation (GEE) statistical model was used to perform pairwise comparisons on each study day. In several pregabalin dosage groups the dosage was escalated during days 1-7, whereas in others pregabalin was initiated at a fixed dosage without escalation. Results: The proportion of patients free of seizures on any treatment day was greater in the combined pregabalin groups compared with baseline. Differences were not observed between the placebo group and baseline. A significantly greater proportion of patients were free of seizures in the combined pregabalin 150-600 mg/day and the pregabalin 600 mg/day fixed-dosage groups compared with the placebo groups from treatment day 2 onward (p < 0.05). From day 8 (coinciding with completion of the 1-week dosage-escalation period in two studies) onward, the proportion of patients free of seizures per day in the pregabalin groups remained relatively constant. Discussion: This exploratory analysis of a refractory population using a rigorous endpoint demonstrates that pregabalin rapidly reduced the frequency of partial seizures. At the dosing schemes most commonly used in placebo-controlled trials, significant seizure-suppressing activity was observed after only 2 days of treatment.

Oral pregabalin as an add‐on treatment for status epilepticus

“…The treatment was efficacious even if administered by the oral route, as already described for topiramate (Towne et al, 2003) and levetiracetam (Rossetti & Bromfield, 2006): this corroborates our recent observation that intravenous administration is not always imperative for refractory SE (Novy et al, 2010). The five responders improved their clinical condition within 24 h of PGB administration; the fast action of this compound in SE reflects recent data on patients with refractory epilepsy (Ramsay et al, 2009). Three further patients responded after 48 h, but since they also received increasing doses of other AEDs, it is difficult to judge the specific role of PGB.…”

“…Pregabalin (PGB) has been on the market since late 2006. Despite being available only as an oral formulation, this compound represents a potentially interesting option for critically ill patients, as it can be titrated quickly (Ramsay et al., 2009), has good oral bioavailability, and is devoid of hepatic interactions (Ben‐Menachem, 2004). We describe here our experience regarding PGB use in subjects with SE.…”

Levetiracetam and pregabalin for antiepileptic monotherapy in patients with primary brain tumors. A phase II randomized study

“…13 PGB modulates Q-type voltage-sensitive calcium channels, 14 does not undergo any metabolic transformation (it has a complete renal excretion), and therefore does not have any impact on the hepatic cytochromic system. 15,16 Despite being limited to oral formulations, it may also be titrated rapidly, exerting therapeutic efficacy within 48 h, 17 and as opposed to gabapentin, which has an identical mechanism of action, PGB does not depend on a saturable intestinal resorption. 18 This study was conducted to determine the safety and efficacy of AED monotherapy with LEV or PGB in patients with primary brain tumors and epilepsy and to collect prospective data on seizure control in brain tumor patients.…”

An open-label, add-on study of pregabalin in patients with partial seizures: A multicenter trial in Greece

“…This 21-week, open label study adds to the accumulating evidence of the efficacy and safety of pregabalin as an adjunctive treatment for partial seizures. [10][11][12][13][25][26][27][28][29][30] As demonstrated by this research in everyday clinical practice, seizure frequency was reduced by 37% with more than half of patients and clinicians reporting ''much improved'' or ''very much improvement.'' Additionally, pregabalin, as an add-on treatment in patients with partial epilepsy, exhibited significant anti-anxiety properties.…”