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.     

Management of Acute Seizure Episodes

Summary: Acute seizures may represent the initial manifestation of epilepsy or isolated events. Urgent treatment of these episodes is indicated to reduce the risk for permanent neurologic damage. Status epilepticus (SE), one form of acute seizure, has an estimated annual incidence of 100,000–150,000 cases per year in the United States. Management of SE focuses on terminating clinical and electrical seizure activity while providing supportive care and identifying the precipitating factors. Physician preference and patient-related factors may dictate the choice of pharmacologic treatment of SE. However, benzodiazepines, which enter the brain rapidly and offer the opportunity for most rapid seizure cessation, are the foundation for SE management. At our institution, first-line treatment consists of i.v. lorazepam followed by a long-acting antiepileptic drug (AED). When i.v. access cannot be attained, high AED blood levels can be rapidly achieved with rectally administered diazepam (DZP). For management of acute repetitive seizures, it is desirable to have an effective drug that can be safely administered by caregivers outside of the hospital setting. Clinical trial data indicate that rectal administration of a prepackaged viscous DZP solution fulfills these criteria. In these studies, rectal DZP gel reduced seizure frequency and recurrence compared to seizure control, improved patient and family quality of life, and was cost-effective because it reduced the need for emergency and inpatient treatment.     

Effectiveness of diazepam rectal gel in adults with acute repetitive seizures and prolonged seizures: a single-center experience

Many adults with epilepsy have breakthrough seizures despite treatment with antiepileptic drugs (AEDs), requiring them to have a rescue medication as part of a comprehensive treatment plan. We evaluated the effectiveness and tolerability of rectal diazepam in the treatment of breakthrough seizures in adult patients with epilepsy. We identified 50 such patients who had used diazepam rectal gel for clusters of seizures defined as acute repetitive seizures, prolonged seizures, or both, in the previous 18 months. Information on diagnoses, dose, frequency of use, reasons for use, safety, and efficacy was collected. Diazepam rectal gel was effective in stopping seizures in 45 patients (90%). Somnolence was reported in most patients, but no other adverse events were reported. Diazepam rectal gel demonstrates efficacy and tolerability as a seizure rescue medication for adult patients with a variety of seizure types, and may help improve quality of life.     

Nonintravenous midazolam versus intravenous or rectal diazepam for the treatment of early status epilepticus: A systematic review with meta-analysis

BackgroundPrompt treatment of status epilepticus (SE) is associated with better outcomes. Rectal diazepam (DZP) and nonintravenous (non-IV) midazolam (MDZ) are often used in the treatment of early SE instead of intravenous applications. The aim of this review was to determine if nonintravenous MDZ is as effective and safe as intravenous or rectal DZP in terminating early SE seizures in children and adults.MethodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and MEDLINE for randomized controlled trials comparing non-IV MDZ with DZP (by any route) in patients (all ages) with early SE defined either as seizures lasting > 5 min or as seizures at arrival in the emergency department. The following outcomes were assessed: clinical seizure cessation within 15 min of drug administration, serious adverse effects, time interval to drug administration, and time from arrival in the emergency department to seizure cessation. Outcomes were assessed using a random-effects Mantel–Haenszel meta-analysis to calculate risk ratio (RR), odds ratio (OR) and mean difference with 95% confidence intervals (95% CIs).ResultsNineteen studies with 1933 seizures in 1602 patients (some trials included patients with more than one seizure) were included. One thousand five hundred seventy-three patients were younger than 16 years. For seizure cessation, non-IV MDZ was as effective as DZP (any route) (1933 seizures; RR: 1.03; 95% CIs: 0.98 to 1.08). No difference in adverse effects was found between non-IM MDZ and DZP by any route (1933 seizures; RR: 0.87; 95% CIs: 0.50 to 1.50). Time interval between arrival and seizure cessation was significantly shorter with non-IV MDZ by any route than with DZP by any route (338 seizures; mean difference: − 3.67 min; 95% CIs: − 5.98 to − 1.36); a similar result was found for time from arrival to drug administration (348 seizures; mean difference: − 3.56 min; 95% CIs: − 5.00 to − 2.11). A minimal difference was found for time interval from drug administration to clinical seizure cessation, which was shorter for DZP by any route than for non-IV MDZ by any route (812 seizures; mean difference: 0.56 min; 95% CIs: 0.15 to 0.98 min). Not all studies reported information on time intervals. Comparison by each way of administration failed to find a significant difference in terms of clinical seizure cessation and occurrence of adverse effects. The only exception was the comparison between buccal MDZ and rectal DZP, where MDZ was more effective than rectal DZP in terminating SE but only when results were expressed as OR (769 seizures; OR: 1.78; 95% CIs: 1.11 to 2.85; RR: 1.15; 95% CIs: 0.85 to 1.54). Only one study was entirely conducted in an adult population (21 patients, aged 31 to 69 years), showing no difference in efficacy or time to seizure cessation after drug administration between intranasal MDZ and rectal DZP.ConclusionsNon-IV MDZ is as effective and safe as intravenous or rectal DZP in terminating early SE in children and probably also in adults. Times from arrival in the emergency department to drug administration and to seizure cessation are shorter with non-IV MDZ than with intravenous or rectal DZP, but this does not necessarily result in higher seizure control. An exception may be the buccal MDZ, which, besides being socially more acceptable and easier to administer, might also have a higher efficacy than rectal DZP in seizure control.This article is part of a Special Issue entitled Status Epilepticus.     

Treatment of partial seizures with gabapentin: double-blind, placebo-controlled, parallel-group study

This double-blind study was conducted to evaluate the efficacy and safety of gabapentin 1200 mg/day and 1800 mg/day (t.i.d.) compared to placebo as an adjunctive therapy in patients with refractory epilepsy. Patients were included when they had partial seizures at least eight times during a 12-week baseline period despite treatment with one to two antiepileptic drugs. After baseline, eligible patients were randomized to gabapentin 1200 mg/day, 1800 mg/day, or placebo for 12-week treatment. The primary end-point, response ratio, was derived from seizure frequencies during treatment and baseline period based upon the seizure daily record by a patient. Of the 209 randomized patients, 86 received gabapentin 1200 mg/day, 41 received gabapentin 1800 mg/day, and 82 received placebo. A statistically significant difference was found between each of the two gabapentin groups and placebo for the primary efficacy end-point, response ratio (P < 0.005) with definite dose-response (P < 0.001). More gabapentin patients reported moderate to marked improvement in seizure frequency and intensity/duration of each seizure than placebo patients. Treatment-related adverse events were reported by approximately 65% of patients receiving gabapentin compared to approximately 46% of patients receiving placebo; somnolence and dizziness were the most common events. Gabapentin 1200 mg/day and 1800 mg/day significantly reduced the frequency of refractory seizures compared to placebo. Favorable tolerability of gabapentin was confirmed also in a Japanese population, consistent with previous global studies.     

A Single-Blind, Crossover Comparison of the Pharmacokinetics and Cognitive Effects of a New Diazepam Rectal Gel with Intravenous Diazepam

Summary: Purpose: The objective of this study was to compare the pharmacokinetics and cognitive effects of a new diazepam (DZP) rectal gel (Diastat®) with intravenously administered DZP.
Methods: Twenty healthy volunteers were enrolled in a single-blind, randomized, double-dummy, two-period, crossover study. Subjects received either 15 mg of DZP rectal gel or 7.5 mg of DZP by intravenous infusion. Blood samples for DZP and desmethyldiazepam analysis were obtained before the dose and from 3 min to 240 h after the dose. Heart rate and blood pressure were measured over the first 24-h period. Subjects also completed five repetitions of a neuropsychological test battery over the first 8-h period.
Results: Diazepam rapidly appeared in plasma after rectal administration, exceeding 200 ng/mL within 15 min and reaching an initial maximum of 373 ng/ml at 45 min and a second maximum of 447 ± 91.1 ng/ml at ∼70 min. The absolute bioavailability of DZP rectal gel was 90.4%. Subjects receiving intravenous DZP were less alert and performed less efficiently on the WAIS Digit Symbol test 6 min after the dose. Subjects receiving DZP rectal gel performed less well on the WAIS Digit Span test 1 h after the dose and required more time to complete the Letter Cancellation and Grooved Pegboard tests 1 and 2 h after drug administration.
Conclusions: Diastat® displayed rapid, consistent absorption and was well tolerated. Alterations in cognition were mild and dissipated within 4 h of drug administration. This new rectal drug-delivery system offers an easy, safe, and bioavailable method to administer DZP.     

Rectal Use of Benzodiazepines

Summary: A number of antiepileptic drugs (AEDs) can be given rectally for either acute seizure control or maintenance therapy. In particular, rectal AED therapy may enable physicians who are not expert in the treatment of status epilepticus (SE) to administer appropriate early therapy. It can also empower parents to provide emergency care when medical help is not available. Rectal administration of parenteral diazepam (DZP) or of specific rectal formulations has been reported effective for aborting and preventing seizures. Adverse events associated with this treatment tend to be rare and mild, although it is important to note the risk for respiratory depression. Lorazepam can also be administered rectally and can produce rapid seizure cessation. It is also associated with fewer side effects than DZP. Although valproate is relatively slowly absorbed after rectal administration, this route has been used to treat SE and for maintenance therapy when oral therapy is not possible. Other AEDs that may be administered rectally include clonazepam, paraldehyde, and carbamazepine.     

Sequential intrarectal diazepam and intravenous levetiracetam in treating acute repetitive and prolonged seizures

In this retrospective study of institutionalized patients with mental retardation, we present the efficacy and safety of sequential treatment with intrarectal diazepam (IRD) gel (Diastat) and intravenous levetiracetam (IVL) in comparison with either treatment alone for acute repetitive or prolonged seizures (ARPS). We defined ARPS as ≥3 seizures of any type within 1 h or a single seizure of any type lasting ≥3 min. Eighty‐eight ARPS episodes were treated in 25 patients (14 female, age 21–72 years), with mainly symptomatic generalized epilepsy. There were no adverse events directly attributable to the administration of IRD or IVL. Seizure recurrence within 4 h of treatment, the primary outcome measure, was significantly lower after combined sequential IRD + IVL treatment (3 of 36) compared to IRD alone (6 of 24, p = 0.048) or IVL alone (10 of 28, p = 0.039). There was no statistically significant difference between the individual IRD and IVL treatments (p = 0.604). The estimated odds ratio (OR) indicated that the risk of seizure recurrence was higher after IRD or IVL monotherapy compared to combined IRD + IVL treatment. Subsequent emergency room (ER) transfers following seizure recurrence were least likely after IVL treatment (10%) compared to combined IRD + IVL (67%) or IRD (83%) treatment. These findings suggest that although IRD or IVL monotherapy is efficacious, the combination is superior in controlling ARPS in this special group of institutionalized patients. In addition, we speculate that a more reliable onset of action after IVL treatment results in rapid seizure control and fewer ER transfers, despite seizure recurrence.     

A comparison of midazolam nasal spray and diazepam rectal solution for the residential treatment of seizure exacerbations

Rectal diazepam is established as a standard rescue or emergency treatment for seizure or status epilepticus; however, the rectal route of administration has not been universally accepted. To determine if an alternative route of administration of a benzodiazepine was equally effective, we compared a novel midazolam HCl concentrated nasal spray (MDZ‐n) with diazepam rectal solution (DZP‐r) in the treatment of prolonged seizures in a residential epilepsy center. In 21 adult patients with medically refractory epilepsy, 124 seizure‐exacerbations were treated by their caregivers, alternatively with 10 mg DZP‐r and 10 mg concentrated MDZ‐n, two or three treatments with each medication for each patient. No difference was demonstrated in efficacy or time to effect between the two drugs. Common treatment emerging adverse effects were drowsiness for both drugs in more than 50% of the administrations, and short‐lasting local irritation after 29% of MDZ‐n. No severe adverse events occurred. The nasal spray was preferred to the rectal solution by 16 of 21 caregivers and patients conjointly. MDZ‐n was equal to DZP‐r with respect to efficacy and side effects in the suppression of seizure exacerbations. The majority of patients and caregivers preferred the nasal spray over the rectal formulation.     

Acute Administration of Benzodiazepines as Part of Treatment Strategies for Epilepsy

Ad‐hoc administration of benzodiazepines (BZD) is well established in status epilepticus, but intermittent BZD use in the treatment of chronic epilepsy is little known beyond catamenial epilepsy. We aim to assess the use of acute drug administration (ADA) in the treatment of 24 patients with epilepsy (9 idiopathic generalized, 14 focal symptomatic/cryptogenic, 1 migraine‐epilepsy) receiving ADA for (1) prevention of generalized tonic‐clonic seizures (GTCS) after minor seizures, (2) prevention of seizures at perceived risk, (3) prevention of seizure clusters. Standard ADA was 10 mg oral clobazam (CLB); one patient received 10 mg rectal diazepam. Concomitant antiepileptic drugs (AED) remained unchanged whenever possible. Ten patients used ADA always correctly, 7 mostly, 7 sporadically or not. Outcome considering seizure control was positive in 44% of all patients (59% of those who actually used ADA): 5 patients seizure free, 1 free of disabling seizures, 4 with >50% reduction in seizure frequency. Eleven had minor or no improvement, 3 patients could not be rated. Thirteen (of 19 possible) patients attempted prevention of seizures or clusters, 10 with full or >50% success (52.6 resp. 76.9%). Prevention of clusters sometimes required higher or repetitive CLB dosing. Self rating of patients who did use ADA was positive or very positive in 88.2%. Retention rate was 66.7% of all patients, and 88.2% of those using ADA. The best results were obtained in idiopathic generalized epilepsy (IGE) patients with seizures habitually triggered by typical factors (sleep deprival, alcohol) but also some others were successful. The only adverse effect was gait ataxia in a multiple‐handicapped patient. ADA is an elegant and often successful but underused treatment option for selected patient groups where it can make the difference between becoming seizure free or not. Depending on the individual case it can be applied as monotherapy or in combination with a basis AED. A controlled investigation should follow.     

Safety and efficacy of intravenous valproate in pediatric status epilepticus and acute repetitive seizures

Summary: Purpose: To evaluate the safety and efficacy of intravenous valproate (VPA) loading in children with status epilepticus (SE) or acute repetitive seizures. Methods: Retrospective review was performed on 40 pediatric patients with intravenous VPA loading. Patients were classified into two groups: SE (n = 18) and acute repetitive seizures (n = 22). Thirty‐one patients were VPA naïve and received a full loading dose of 25 mg/kg; nine had subtherapeutic plasma VPA levels and received a partial loading dose. Average infusion rate was 2.8 mg/kg/min. Heart rate and blood pressure were measured before, during, and after infusion. Results: Intravenous VPA loading stopped seizures in 18 patients with SE within 20 min. All 18 patients regained baseline mental status within 1 h of seizure cessation. Among 22 patients with acute repetitive seizures, only one had further seizures after VPA infusion. One patient in the SE group complained of transient tremors. No significant changes in blood pressure or heart rate were found in either group. Postinfusion plasma VPA levels ranged from 51 to 138 μg/ml (mean ± SD = 88 ± 21.5 μg/ml). Conclusions: Intravenous VPA loading is safe and effective for treating acute seizure emergencies in children.     

Felbamate Monotherapy: Implications for Antiepileptic Drug Development

Summary: We studied the effect of felbamate (FBM) monotherapy on seizure rate in patients with partial and secondarily generalized seizures undergoing presurgical monitoring at a single site. The study design was a double-blind placebo-controlled parallel monotherapy trial. Forty patients whose seizures had not been controlled by standard antiepileptic drugs (AEDs) were randomized. Seizure type was confirmed by video-EEG monitoring. All baseline AEDs were discontinued, and patients were drug-free for 5.3 ± 2.4 days before randomization to FBM or placebo. After a 4-day titration, seizures were counted for 14 days. Patients receiving FBM had significantly lower seizure rates, whether all randomized patients, patients who survived titration, or study completers were compared. Eight of 19 placebo patients randomized to placebo, as compared with 13 of 21 receiving FBM, completed the 18-day study. Two FBM patients dropped out due to seizures, and 6 dropped out due to side effects, including anxiety, difficulty sleeping, abdominal discomfort, acute psychosis, and orobuccal dyskinesias. Ten placebo patients met the criteria for premature discontinuation owing to seizures, and 1 had an episode of panic. There was no evidence of hepatic or hematologic toxicity. FBM reduces seizure frequency in patients with localization-related epilepsy.     

Febrile seizures: treatment and prognosis

Recent epidemiologic data indicate that the vast majority of children with febrile seizures have a normal longterm outcome. A precise knowledge of the short- and long-term outcome with or without treatment, and short- and long-term side effects is an important prerequisite for assessing the various treatment strategies. We focus on the impact of short-term or prophylactic treatment on the short- and long-term outcome of various types of febrile seizures. There is universal agreement that daily prophylaxis with antiepileptic agents should never be used routinely in simple febrile seizures, but only in highly selected cases, if at all. Intermittent diazepam (DZP) prophylaxis at times of fever may or may not reduce the recurrence rate, but it does not appear to improve the long-term outcome as compared with short-term seizure control. The treatment may be used to reduce the recurrence rate for a small arbitrarily defined group with multiple simple febrile seizures, complex febrile seizures, especially focal, prolonged or both, febrile status, and when parental anxiety is severe. However, there is no evidence that treatment of simple febrile seizures can prevent the rare cases of later epilepsy, and many children with complex febrile seizures have a benign long-term outcome, even without treatment. Many prefer a "wait and see" policy. An attractive alternative is to treat new febrile seizures with rectal DZP in solution at seizure onset, given by the parents at home to prevent febrile status. Newer, less well documented short-term strategies include nasal, oral, or rectal administration of other benzodiazepines. Short-term seizure control of febrile status and careful parental counseling are the two most important targets of treatment.     

Intravenous levetiracetam in children with epilepsy

Intravenous levetiracetam recently became available for use in patients aged >16 years. There are few data about its safety and efficacy in children. We retrospectively analyzed data from children treated with intravenous levetiracetam. Ten patients (6 female, 4 male), aged 3 weeks to 19 years, were treated with intravenous levetiracetam at a mean dose of 50.5 mg/kg/day for a mean duration of 4.9 days. Four patients received intravenous levetiracetam for acute repetitive seizures/status epilepticus, and three as replacement for oral levetiracetam because administration of oral levetiracetam was temporarily infeasible. One patient each received intravenous levetiracetam for seizure prophylaxis during brain biopsy, as maintenance treatment after acute seizures, and as substitute for sodium valproate. Three of four patients with acute repetitive seizures/status epilepticus became seizure-free; the fourth patient had a partial reduction in seizure frequency. All three patients who received intravenous levetiracetam as substitute for oral levetiracetam tolerated the switch well. The other three patients were seizure-free on intravenous levetiracetam. No serious adverse effects were observed, and all patients completed treatment with intravenous levetiracetam for the intended period. Intravenous levetiracetam may be effective in various clinical situations requiring intravenous administration of an antiepileptic drug.     

Status Epilepticus and Acute Repetitive Seizures in Children, Adolescents, and Young Adults: Etiology, Outcome, and Treatment

Summary: Status epilepticus (SE) is one of the most common neurologic emergencies in children, adolescents, and young adults. SE may be due to acute neurologic conditions such as meningitis, encephalitis, or stroke, complicated febrile seizures, intractable epilepsy, degenerative diseases, intoxication, or may be the first manifestation of epilepsy. Initial treatment of convulsive SE is usually with an intravenous benzodiazepine (BZD) [lorazepam (LZP) or diazepam (DZP)], phenobarbital (PB), or phe-nytoin (PHT). LZP is less likely to cause respiratory depression than DZP and is therefore preferred. Sequelae and risk for recurrence of SE are primarily related to the underlying cause. Refractory SE (RSE) is most often symptomatic of an acute neurologic condition or neuro-degenerative disease. Treatment for RSE is difficult, usually requiring intensive support of vital functions. Reported treatments for RSE include very high dose PB, continuous infusions of pentobarbital or BZDs (DZP, mi-dazolam), lidocaine, inhalation anesthesia, and propofol. Outcome is related to underlying cause. Nonconvulsive SE may present as confusion or may mimic psychiatric illness. Response to BZDs is usually rapid but may not be sustained. Rapid initiation of oral or rectal valproate may be useful. Epilepsia partialis continua (EPC) is almost always due to an acute or chronic destructive lesion. Surgical treatment may be the only effective modality in some children with EPC. Acute treatment of breakthrough seizures and clusters of seizures at home with rectal BZDs (usually DZP, 0.2–0.5 mg/kg) may prevent progression to SE in some children and adolescents and reduce the need for visits to emergency facilities.     

Early coadministration of clonazepam with sertraline for panic disorder.

BACKGROUND: There is debate about combining benzodiazepines with selective serotonin reuptake inhibitors in the acute treatment of panic disorder. Although this medication combination is widely used in clinical practice, there is no well-tested, optimal method of coadministering these medications for the treatment of panic disorder. The purpose of this study was to test the efficacy of early coadministration of clonazepam with sertraline in the treatment of panic disorder. METHODS: Fifty patients with panic disorder were randomized into a double-blind clinical trial. Patients received open-label sertraline for 12 weeks (target dose, 100 mg/d), and in addition were randomized to groups receiving either 0.5 mg of active clonazepam 3 times daily or placebo clonazepam for the first 4 weeks of the trial. The clonazepam dose was then tapered during 3 weeks and discontinued. RESULTS: Thirty-four (68%) of 50 patients completed the trial. Drop-out rates were similar in the sertraline/placebo vs the sertraline/clonazepam group (38% vs 25%) (P =.5). An intent-to-treat analysis (on last observation carried forward data) revealed a much greater proportion of responders in the sertraline/clonazepam compared with the sertraline/placebo group at the end of week 1 of the trial (41% vs 4%) (P =.003). There was also a significant between-group difference at the end of week 3 with 14 (63%) of 22 of the sertraline/clonazepam group responding to treatment vs 8 (32%) of 25 of the sertraline/placebo group (P =.05). This difference was not observed at other times during the trial. CONCLUSION: These data indicate that rapid stabilization of panic symptoms can be safely achieved with a sertraline/clonazepam combination, supporting the clinical utility of this type of regimen for facilitating early improvement of panic symptoms relative to sertraline alone.     

Adult patient perceptions of emergency rectal medications for refractory seizures

Background. Rectally administered benzodiazepine antiepilepsy drugs (AEDs) are a safe and effective therapy for acute repetitive seizures in patients on stable maintenance AEDs. Such medication provides an earlier treatment option for seizure control prior to emergency department (ED) visitation and may be administered outside of the hospital in carefully selected patients. The use of rectal medications, however, has a perceived association with fear and embarrassment. This study sought to address patient attitudes toward rectally delivered AEDs. Methods. A written, eight-question survey regarding adult patient attitudes toward rectal medication and ED visits was prospectively administered to 91 consecutive epilepsy patients in an epilepsy-based practice setting. Primary caretakers responded when patients were unable to do so. RESULTS: Forty-eight female and thirty-two male survey responses were analyzed. The mean patient population was age 42.7 years with epilepsy for 23.7 years on 1.7 AEDs with a seizure frequency of 6.6/month. The majority had partial and generalized tonic-clonic seizures and had obtained at least a high school education. Three patients (6%) had symptomatic generalized epilepsy and required caretaker responses. Eleven of ninety-one (12.1%) surveys were incomplete for analysis. Seventy-six of eighty (95%) respondents completed at least 50% of the survey questions. Forty-three of sixty-four (67.2%) respondents were not embarrassed by rectal AEDs, and did not fear being teased by others. Additionally, most felt rectal AEDs were a good option in epilepsy management, yet would prefer a private setting for administration. Both seizures and rectal AED use appeared to be equally embarrassing to patients. While 53 of 76 (69.7%) reported ED visitation for seizures at some time, the vast majority (56/60, 93.3%) reported they would prefer treatment outside the hospital, as opposed to ED transport. Conclusions. The results from this adult patient survey suggest that individuals with epilepsy do not object to earlier administration of emergency rectal seizure medication relative to ED visitation. An undesirable perception of rectal medications in seizure emergencies does not appear to be limited by patient acceptance.     

The Use of Diazepam and Clonazepam in Epilepsy

Summary: This article reviews the pharmacokinetics, efficacy, and tolerability of diazepam (DZP) and clonazepam (CZP) in the treatment of epilepsy, with special emphasis on the management of acute seizures and status epilepticus. In these conditions, i.v. DZP and CZP are first-line agents, resulting in rapid and lasting control in 70–85% of cases. However, the response rate depends largely on the type of epilepsy in epileptics or the underlying cause of seizures in nonepileptic patients. Because of the rapid redistribution pattern of these antiepileptic drugs (AEDs) from the" brain, co-administration of a long-acting drug is often required. In contrast, continuous infusion of DZP and CZP is no longer generally recommended. Rectal DZP instillation is a valuable alternative for immediate treatment at home for serial seizures and prophylaxis of febrile seizures. The side effects of i.v. DZP and CZP include cardiorespiratory depression, sedation, and paradoxical effects such as precipitation of tonic status epilepticus in Lennox-Gastaut syndrome. Although both AEDs are currently employed for the management of acute seizures, only CZP is also used for oral treatment of chronic epilepsy, especially with refractory absence, myoclonic, atonic, and partial seizures. Side effects and the development of tolerance, however, limit the usefulness of CZP for chronic treatment.     

Evolving antiepileptic drug treatment in juvenile myoclonic epilepsy

BACKGROUND: In the face of availability of newer antiepileptic drugs (AEDs) such as lamotrigine and topiramate, there is need to reassess the role of older AEDs in the treatment of juvenile myoclonic epilepsy (JME). OBJECTIVES: To explore whether lamotrigine and topiramate monotherapy or polytherapy can be effective options in the treatment of JME, and to determine whether older AEDs, such as phenytoin and carbamazepine, have a role in the treatment of JME. DESIGN: A retrospective cohort study. SETTING: A large academic teaching hospital. PATIENTS: Seventy-two consecutive JME patients treated with valproic acid, lamotrigine, topiramate, phenytoin, or carbamazepine between April 1, 1991, and March 31, 2001. METHODS: We compared the efficacy of valproic acid, lamotrigine, and topiramate monotherapy or polytherapy in the control of different seizure types of JME, and compared their efficacy and tolerability with the efficacy and tolerability of phenytoin and carbamazepine. RESULTS: Seizure outcome did not differ when patients receiving valproic acid monotherapy (n = 36) were compared with those receiving lamotrigine monotherapy (n = 14), and when patients receiving valproic acid polytherapy (n = 22) were compared with those receiving lamotrigine polytherapy (n = 21) or topiramate polytherapy (n = 15) (P>.05 for all). The combined data of myoclonic seizure control by all 3 AEDs were poorer when compared with the combined data of generalized tonic-clonic seizure control by all 3 AEDs (P =.03), but not when compared with the combined data of absence seizure control by all 3 AEDs (P =.43). Valproic acid, lamotrigine, and topiramate, when compared with phenytoin or carbamazepine, demonstrated significantly better control of myoclonic seizures (P<.01 for all), but not of generalized tonic-clonic seizures (P>.11 for all). CONCLUSIONS: Lamotrigine and topiramate are effective alternative options to valproic acid in the treatment of JME. Lamotrigine is an effective option as monotherapy and polytherapy. Topiramate is an effective option as polytherapy, but more data are needed to determine if it is an effective option as monotherapy. More effective therapy is needed to improve myoclonic seizure control. Older AEDs, such as phenytoin and carbamazepine, may not be indicated in JME patients.