دانلود رایگان ترجمه مقاله آزمایش بالینی پره گابالین به عنوان یک درمان تکمیلی در کودکان مبتلا به صرع مزمن – 2013

کارآزمایی بالینی پرگابالین به عنوان یک درمان افزودنی در کودکان مبتلا به صرع مزمن

Clinical trial of pregabalin as an add-on therapy in children with refractory epilepsy

Abstract

Epilepsy is the most common neurological disorder worldwide. One-third of epileptic patients do not respond after treatment with first- or second-line antiepileptic drugs. Pregabalin is a novel antiseizure drug with established anxiolytic and analgesic efficacy. In this study, we evaluated the efficacy and tolerability of pregabalin as an adjunctive therapy in a group of children with intractable epilepsy. From October 2011 to September 2012, 67 children with refractory epilepsy who visited the pediatric neurology clinic of Mofid Children’s Hospital were enrolled in this study. The patients were treated with pregabalin. Reduction in seizure frequency and severity were compared after 1 and 6 mo of treatment initiation. During follow-up, >50% reduction in seizure frequency or severity was observed as a response to the drug. Of the 60 children who reached the last stage, 29 (48.3%) were boys and 31 (51.7%) were girls. The age of the children ranged between 6 mo and 16 yr, with a mean age of 71 ± 42.9 mo. Pregabalin reduced seizure frequency up to 2.41 ± 2.38 (48% decline) and 2.75 ± 2.38 (40.86% decline) after 1 and 6 mo of treatment initiation, respectively. There was a significant difference between seizure frequency at 1 (P < 0.001) and 6 mo (P < 0.001) after pregabalin initiation compared with the initial attacks. Increased appetite, frequent urination, hallucinations, and headache were the most common side effects in our patients, with a complication rate of 18.33%. Thus, pregabalin seems to be effective and well tolerated for seizure control in children with intractable epilepsies.

1 Introduction

Approximately 50 million people suffer from epilepsy worldwide, indicating that it is the most common neurological disorder. Only two-thirds of epileptic patients respond after treatment with first- or second-line antiepileptic drugs (AEDs) despite the presence of newgeneration anticonvulsants. Multiple drug therapy using adequate AEDs with suitable safety and tolerability is another choice for the treatment of patients with epilepsy [1,2].

Pregabalin (PGB) is a novel AED, which has established anxiolytic and analgesic impressions in preclinical animal studies [3]. PGB is structurally similar to gamma-aminobutyric acid (GABA) but is inactive against GABA receptors [4]. PGB has a favorable pharmacokinetic profile, including a linear doseconcentration curve, with an effective range of 150– 600 mg/day; rapid and extensive absorption after oral consumption, which is not affected by food; high bioavailability of approximately 90%, which reaches peak plasma concentration 1 h after oral dosage; and a half-life of 6 h [5].

PGB does not cause relevant pharmacokinetic interactions with simultaneously administered anticonvulsants because of the lack of cytochrome P450 induction, protein binding, and pharmacokinetic interaction [6]. PGB has pharmacological features similar to those of gabapentin (GBP), with a 3-10-fold higher potency. Both these molecules connect the a2d subunit of voltage-related calcium channels and carry out their actions through calcium channel turnover, which results in decreased calcium influx and consequently diminution of presynaptic neurotransmitter release [7,8].

Several randomized controlled trials have shown that PGB can be used as an adjunctive therapy for partial epilepsies, with favorable efficacy and tolerability [9]. However, limited literature is available on the efficacy of PGB as an adjunctive therapy in epileptic children experiencing different types of seizures. Thus, in this study, we evaluated the efficacy and tolerability of PGB as an adjunctive treatment in a group of children with intractable epilepsy