Rectal diazepam gel for treatment of acute repetitive seizures in adults

OBJECTIVE: To evaluate the efficacy and tolerability of diazepam (DZP) rectal gel (Diastat; Elan Pharmaceuticals, Dublin, Ireland) for the treatment of acute repetitive seizures in adult patients in 2 multicenter, double-blind, placebo-controlled parallel studies. METHODS: Ninety-six adults 18 years or older with acute repetitive seizures, 70 of whom received treatment, were randomized into the 2 studies. Active and placebo medications were supplied in prefilled, identical-appearing delivery systems. In study 001, patients received a second dose 4 hours after the initial treatment. Patients in study 003 received only 1 treatment. Patients were observed for 12 hours after the first dose. RESULTS: There was a significant reduction in seizure frequency in patients who received DZP compared with the placebo group. The median number of seizures per hour in the group treated with DZP rectal gel was 0.00, vs 0.13 in the placebo group (P =.002). In addition, significantly more DZP rectal gel-treated patients remained seizure-free during the 12-hour observation period (71% [22/31] vs 28% [11/39]). Using Kaplan-Meier life-table analysis, time to the next seizure was found to be significantly longer in DZP rectal gel-treated than placebo-treated patients (P<.001). Global assessment as provided by the caregivers was in favor of DZP rectal gel for both study 001 (P =.17) and study 003 (P =.02). Dizziness and somnolence were the only central nervous system adverse events that occurred more frequently in patients receiving DZP rectal gel than in those receiving placebo. CONCLUSION: In adults, rectal DZP formulated as Diastat significantly reduced the likelihood of seizure recurrence during an episode of acute repetitive seizures, with minimal safety concerns.     

Valproate versus diazepam for generalized convulsive status epilepticus: a pilot study

Background and purpose: Evidence‐based data to guide the management of status epilepticus (SE) after failure of primary treatment are still scarce and the alternate needs to be found when phenytoin (PHT) is not available or contraindicated. Comparison of intravenous (IV) valproate (VPA) and diazepam (DZP) infusion has not been conducted in adults with SE. This prospective randomized controlled trial is thus designed to evaluate the relative efficacy and safety of IV VPA and continuous DZP infusion as second‐line anticonvulsants. Methods: After failure of first‐line anticonvulsants treatment, patients with generalized convulsive status epilepticus (GCSE) were randomized to receive either IV VPA or continuous DZP infusion. Primary outcome was the proportion of patients with effective control. Side effects were also evaluated. Results: There were 66 cases enrolled, with the mean age of 41 ± 21 years. Seizure was controlled in 56% (20/36) of the DZP group and 50% (15/30) of the VPA group (P = 0.652). No patient in the VPA group developed respiratory depression, hypotension, or hepatic dysfunction, whereas in the DZP group, 5.5% required ventilation and 5.5% developed hypotension. Time (hour) for regaining consciousness after control was near‐significantly longer in the DZP group [13(3.15–21.5)] than in the VPA group [3(0.75–11)] (P = 0.057). Virus encephalitis and long duration of GCSE were independent risk factors of drug resistance. Conclusions: Both IV VPA and continuous DZP infusion are effective second‐line anticonvulsants for GCSE. IV VPA was well tolerated and free of respiratory depression and hypotension, which may develop in the DZP group. Outcome parameters were not significantly different between groups.     

Lorazepam versus diazepam for the treatment of status epilepticus

A retrospective study was performed to compare intravenous lorazepam and intravenous diazepam in the treatment of status epilepticus. Forty-five episodes of status epilepticus in children between the ages of 2 weeks and 18 years were reviewed. Lorazepam and diazepam proved similar in efficacy of seizure control and incidence of adverse effects. The dose of lorazepam required to control status epilepticus ranged from 0.03 to 0.22 mg/kg with a mean of 0.11 mg/kg (S.D. = 0.05 mg/kg). Among children treated with lorazepam, only children younger than 2 years of age had respiratory depression which required intubation.     

Late-life absence status epilepticus: a female disorder?

We report on three women and a review of the literature on absence status epilepticus over the age of 50 years. Our aim was to characterize the male-female ratio in this condition. Out of 16 studies on absence status epilepticus over the age of 50, including our cases, a female dominance was found in 15. We found altogether, 104 (71%) females and 42 (29%) males. This gender difference is highly significant (p < 0.00001). We conclude that absence status epilepticus over the age of 50 is predominantly a female disorder.     

Intravenous sodium valproate in mainland China for the treatment of diazepam refractory convulsive status epilepticus

The purpose of this study was to identify the short-term safety and efficacy of treating patients with intravenous (i.v.) sodium valproate (VPA) for diazepam (DZP) refractory convulsive status epilepticus (CSE). We prospectively registered 48 patients with refractory CSE who were treated at West China Hospital with i.v. VPA (30 mg/kg, 6 mg/kg per hour) after a loading dose of i.v. DZP and intramuscular phenobarbitone (PBT) failed. VPA stopped seizures in 87.5% of patients within 1 h, and patients regained baseline mental status within 1 h of seizure cessation. CSE did not recur in patients within the next 12 h, and no significant VPA-related systemic or local side effects were found during their hospital stay. In conclusion, this study suggests that i.v. VPA is a promising option for DZP refractory CSE in mainland China, since i.v. PBT is unavailable in most hospitals, and anesthesia is unacceptable to most of the Chinese population.     

Adult onset absence status: a report of six cases

The six cases which we report show the range of confusional states which may be seen in absence status. They also illustrate the importance of electroencephalography in the diagnosis of acute confusional states. In all cases the absence status began in adult life and in one of these it was the first manifestation of epilepsy. Two patients became schizophrenic concurrently with the onset of absence status. The preventive treatment of absence status remains problematic. In particular, clonazepam and valproic acid were ineffective in our series. The attack of absence status may respond to intravenous diazepam or oral clonazepam. In our experience, if the patient is able to take oral medication during absence status, oral clonazepam stops the status within one to two hours. This avoids the potential complications of intravenous diazepam.     

Levetiracetam in the treatment of status epilepticus in adults: a study of 13 episodes

Treatment of status epilepticus (SE) has changed little over the last two decades, but the burden of this condition remains important. There is thus a need for alternative pharmacological therapies. Levetiracetam (LEV) has a wide spectrum of action and a favorable pharmacokinetic profile; however, little data exist regarding its use in SE. We identified patients with SE who received LEV, in a database comprising 127 SE episodes. Demographic, clinical and pharmacological data were analyzed, and compared to a control group consisting of 2 subjects from the database for each LEV patient, matched for age and sex. We identified 13 SE episodes occurring in 12 patients (10% of the database). Demographic, etiologic and clinical characteristics and outcome did not differ between the groups. Daily LEV dose ranged between 1,000-6,000 mg. Three patients were probable responders (23%), 1 responded to the treatment but subsequently died (8%), 4 were non-responders (31%, 1 died), and 5 had an undetermined response (38%). LEV may represent a useful alternative in the treatment of SE, particularly if a parenteral form of administration becomes available; to better define its role in this setting, prospective studies are needed.     

Psychosis-like absence status of elderly patients: successful treatment with sodium valproate.

Absence status and psychosis-like behaviour and continuous spike-and-wave EEG activity in two elderly women is reported. Once the correct diagnosis was made, the patients were successfully treated with sodium valproate. Differential diagnosis between absence status and psychotic syndromes is emphasised.     

Lorazepam and diazepam in the treatment of neurotic anxiety: a double-blind trial.

Fifty-eight neurotic patients with intense anxiety were treated with either lorazepam or diazepam in a double blind between-patients trial. Statistical analysis indicated that the two groups were homogeneous before treatment and that the results of treatment were similar for both drugs. According to the global rating of illness week after week, after four weeks of treatment more patients on lorazepam than on diazepam were normal or had mild illness (82.1% vs. 70.8%). In the investigators' judgment, 71.9% of the patients treated with lorazepam had an excellent or good response compared with 56.7+ of those treated with diazepam. The mean reduction in score on the Hamilton Anxiety Scale was 17.7 for lorazepam and 16.5 for diazepam. However, none of the above differences in results were statistically significant. The largest dose of lorazepam required in treatment was 6 mg, compared with 30 mg of diazepam. Two patients treated with lorazepam had side effects, against six with diazepam. Six patients in the diazepam group did not complete the trial, including three who discontinued because of side effects (rash, tremors, agitation); no patients in the lorazepam group dropped out.     

Rectal diazepam gel for treatment of acute repetitive seizures. The North American Diastat Study Group.

The purpose of these investigations was to determine from combined data the response to rectal diazepam (DZP) gel (Diastat [Athena Neurosciences, South San Francisco, CA]) in home treatment of children with episodes of acute repetitive seizures (ARS). A subset of patients aged 2-17 years were selected from two prospective placebo-controlled studies of children and adults. In both studies a prospective, double-blind, placebo-controlled design was used. The treatment groups (68 DZP; 65 placebo) did not differ significantly in age, race, seizure type or etiology, or in the median number of ARS episodes per month before study entry. DZP-treated children demonstrated a significant reduction in median seizure frequency compared with the placebo group (0.00 vs 0.25 seizures per hour, P = 0.001). Significantly more DZP-treated children remained seizure free during the observation period (40 vs 20, P = 0.001). Somnolence was the only adverse effect present significantly more often in the DZP-treated children (25.0% vs 7.7%, P = 0.0095). There were no instances of serious respiratory depression. Rectal DZP was demonstrated to be an effective and safe treatment to abort an episode of ARS in a child and, additionally, lessened the likelihood of seizure recurrence within the next 12 hours.     

Response of status epilepticus induced by lithium and pilocarpine to treatment with diazepam

Status epilepticus (SE) was induced in rats by administration of 3 mmol/kg lithium chloride followed 24 h later by injection of 25 mg/kg pilocarpine. Treatment with 20 mg/kg diazepam was initiated at the time each of four EEG patterns was seen: (i) discrete electrographic seizures; (ii) waxing and waning epileptiform activity; (iii) continuous, high-amplitude, rapid spiking; and (iv) periodic epileptiform discharges (PEDs) on a relatively flat background. Success of diazepam in stopping all seizure activity was predicted by the EEG pattern seen at the time of treatment. All rats treated while displaying discrete electrographic seizures had status stopped with diazepam, but only three of six with waxing and waning epileptiform activity and one of six each with continuous spiking and PEDs. Rats which continued to seize had a decrease in spike amplitude of 74.8 +/- 18.25% following diazepam injection. These data confirm the clinical impression that the longer the duration of status epilepticus, the more difficult it is to control and suggest that the EEG pattern at the time of treatment predicts the probability of success.     

单纯地西泮与地西泮联合丙戊酸治疗癫(癎)持续状态的疗效比较

目的 比较单纯地西泮和地西泮联合丙戊酸钠治疗癫(癎)持续状态(SE)的疗效.方法 选择成人SE患者35例,分成地西泮组(给予地西泮静脉治疗)和地西泮联合丙戊酸钠组(地西泮联合丙戊酸钠静脉治疗)两组,观察两组的疗效.结果 两组治疗的有效率差异无统计学意义,地西泮联合丙戊酸钠组72 h内复发率低于地西泮组(P＜0.05).结论 地西泮联合丙戊酸钠治疗可降低SE患者的复发.