Dosing feasibility and tolerability of intranasal diazepam in adults with epilepsy.

OBJECTIVE: To determine the feasibility of administering a diazepam nasal spray formulation (diazepam-NS) to adults with epilepsy during a generalized tonic-clonic seizure or in the postictal period following a tonic-clonic or other seizure type, to assess pharmacokinetics and to assess tolerability. METHODS: An open-label study was conducted in patients admitted to the epilepsy monitoring unit. Eligible patients received a single dose of diazepam-NS approximating 0.2 mg/kg. Plasma diazepam concentrations were measured serially up to 12 h postdose, and maximum observed plasma concentration (Cmax ); time to maximum concentration (Tmax ); and the area under the plasma concentration-time curve for time zero to last sampling time (AUC0-12 ) were estimated and dose-normalized. Pharmacodynamic assessments included Kaplan-Meier analysis to determine the time-to-next seizure. Safety and tolerability were assessed. RESULTS: Of the 78 patients who consented, 30 had treatment and pharmacokinetic data. Ten patients were treated during a convulsive tonic-clonic seizure, seven within 5 min following the last clonic jerk, and 13 in the postictal period ≥ 5 min after a tonic-clonic or following other seizure-types. Diazepam median Tmax was 45 min. Dose-normalized mean Cmax and AUC0-12 values of diazepam were comparable among patients regardless of the timing of diazepam-NS administration in relation to seizure. Of those treated, 65% were seizure-free during the 12-h observation period and 35% had post-dose seizures. Treatment was well tolerated, with no unexpected safety findings: 74% had mild and 25% had moderate adverse events. Nasopharyngeal signs were resolved by 12 h postdose. SIGNIFICANCE: Diazepam can be delivered in effective therapeutic concentrations by a nasal spray device during the convulsive phase of tonic-clonic seizures or in the postictal periods following tonic-clonic or other seizure types.

Clobazam for patients with Lennox-Gastaut syndrome and epilepsy.

Lennox-Gastaut syndrome (LGS) is a form of childhood epileptic encephalopathy that continues to be challenging to treat and manage. The available treatments have failed to provide good control for patients with this devastating epilepsy syndrome. Clobazam is a promising antiepileptic medication, given its effectiveness and relatively low rates of adverse effects. It has been studied and used in several countries for the treatment of refractory seizures, including those that occur with LGS. Clobazam (Onfi™; Lundbeck Inc., IL, USA) has been studied in the USA to demonstrate its efficacy and safety for the treatment of seizures associated with LGS, and Phase II and III trials have recently been completed. This article will explore the use of clobazam in the treatment of LGS and present the results of Phase II and III studies, along with an overall summary of the treatment of LGS, as well as the possible role of clobazam in a treatment algorithm. We based this article on the most relevant reports with the term 'clobazam' found through a Medline search (1966-2011).

Problems and controversies in status epilepticus: a review and recommendations.

Status epilepticus (SE) is a neurologic emergency that require immediate vigorous treatment in order to prevent serious morbidity or even death. Several investigators have suggested that the underlying etiology is the primary determinant of outcome. We believe that this may be true in aggressively treated SE, but not when the treatment is less than optimal. In this article, we will discuss the factors that have been implicated in affecting SE outcomes, and argue, on the basis of both human and experimental animal data, that aggressive treatment is necessary and appropriate for all presentations of SE in order to maximize the probability of a successful outcome even when the etiology suggests a poor prognosis.