Antiepileptic Drugs Useful in Status Epilepticus

2019 ◽  
pp. 513-525
Author(s):  
Daniel H. Lowenstein ◽  
Roger P. Simon
Neurology ◽  
2019 ◽  
Vol 92 (20) ◽  
pp. e2339-e2348 ◽  
Author(s):  
Iván Sánchez Fernández ◽  
Marina Gaínza-Lein ◽  
Nathan Lamb ◽  
Tobias Loddenkemper

ObjectiveCompare the cost and effectiveness of nonbenzodiazepine antiepileptic drugs (non-BZD AEDs) for treatment of BZD-resistant convulsive status epilepticus (SE).MethodsDecision analysis model populated with effectiveness data from a systematic review and meta-analysis of the literature, and cost data from publicly available prices. The primary outcome was cost per seizure stopped ($/SS). Sensitivity analyses evaluated the robustness of the results across a wide variation of the input parameters.ResultsWe included 24 studies with 1,185 SE episodes. The most effective non-BZD AED was phenobarbital (PB) with a probability of SS of 0.8 (95% confidence interval [CI]: 0.69–0.88), followed by valproate (VPA) (0.71 [95% CI: 0.61–0.79]), lacosamide (0.66 [95% CI: 0.51–0.79]), levetiracetam (LEV) (0.62 [95% CI: 0.5–0.73]), and phenytoin/fosphenytoin (PHT) (0.53 [95% CI: 0.39–0.67]). In pairwise comparisons, PB was more effective than PHT (p = 0.002), VPA was more effective than PHT (p = 0.043), and PB was more effective than LEV (p = 0.018). The most cost-effective non-BZD AED was LEV (incremental cost-effectiveness ratio [ICER]: $18.55/SS), followed by VPA (ICER: $94.44/SS), and lastly PB (ICER: $847.22/SS). PHT and lacosamide were not cost-effective compared to the other options. Sensitivity analyses showed marked overlap in cost-effectiveness, but PHT was consistently less cost-effective than LEV, VPA, and PB.ConclusionVPA and PB were more effective than PHT for SE. There is substantial overlap in the cost-effectiveness of non-BZD AEDs for SE, but available evidence does not support the preeminence of PHT, neither in terms of effectiveness nor in terms of cost-effectiveness.


Author(s):  
Keerthana Brattiya ◽  
Bhuvaneshwari K

This case study is to report and explore the etiology of a case of refractory seizures due to overdosage of phenytoin tablets. A case report from the Department of Neurology generated through voluntary adverse drug reaction (ADR)reporting stated phenytoin overdosage leading to refractory status epilepticus which did not respond to any of the antiepileptic drugs. A 33-year-old female patient with the history of consumption 15 tablets of phenytoin and a metal ring as part of a suicidal bid a month ago, presented with unconsciousness, persistent seizures, and gangrene of fingers. Magnetic resonance imaging showed generalized atrophic changes of the cerebrum and cerebellum. Electroencephalogram suggested multifocal onset status epilepticus. The patient did not respond to standard emergency treatment of status epilepticus with known antiepileptic drugs and was treated with thiopentone infusion under mechanical ventilation, which controlled her seizures as long as she was maintained under the infusion. Causality analysis using the World Health Organization scale categorizes this ADR as “possible”, as the patient is a known case of seizure disorder with additional cerebral changes. Hence, the disease could have had an influence over the toxic reaction. To conclude, seizures are a rare complication of phenytoin. Seizures can be prevented by evaluating therapeutic plasma concentration of phenytoin. In this case, the patient was on chronic treatment, and due to intentional toxicity, she progressed to a refractory state of seizures. This could have occurred because of the unique kinetic profile of phenytoin, small therapeutic index, genetic variation in drug metabolizing enzymes, and saturated sodium channels.


2019 ◽  
Vol 101 ◽  
pp. 106787
Author(s):  
Sunee Lertsinudom ◽  
Phiangkwan Nakornratanachai ◽  
Nanthaphan Chainirun ◽  
Somsak Tiamkao ◽  
Ratchadaporn Soontornpas

CNS Drugs ◽  
2017 ◽  
Vol 31 (4) ◽  
pp. 327-334 ◽  
Author(s):  
Isabelle Beuchat ◽  
Jan Novy ◽  
Andrea O. Rossetti

2017 ◽  
Vol 98 (5) ◽  
pp. 729-732 ◽  
Author(s):  
Sh Y Melikova

Aim. To investigate the peculiarities of focal epilepsy in pregnant women. Methods. 70 pregnant women with symptomatic focal epilepsy during the period from 2013 to 2017 were studied. Results. The average age at the onset of epilepsy was 18.2±0.6 years. The average duration of epilepsy by the time of pregnancy was 6.6±0.7 years. 15 (21.4±4.9%) women remained seizure-free during pregnancy. Seizures during pregnancy were observed in 55 (78.6±4.9%) women: seizure frequency increased in 22 (31.4±5.5%) cases, decreased in 17 (24.3±5.1%), remained unchanged in 8 (11.4±3.8%), in 8 (11.4±3.8%) women the onset of epilepsy occurred during pregnancy. 72.7% of women who were seizure-free for 1 year prior to pregnancy remained seizure-free during pregnancy. In 21 (40.4%) of 52 women with epilepsy diagnosed prior to pregnancy and treated with antiepileptic drugs, the increase of seizure frequency was observed, which can be explained by non-compliance with the regimen and therapy and sleep deprivation in 15 (71.4%) of them. Generalized convulsive status epilepticus during pregnancy was observed in 1 (1.4±1.4%) woman after a sudden withdrawal of the antiepileptic drug. Conclusion. The risk of seizures during pregnancy is lower in women who were seziure-free for 1 year prior to pregnancy; non-compliance with the regimen and therapy and sleep deprivation may lead to worsening of epilepsy during pregnancy.


Folia Medica ◽  
2020 ◽  
Vol 62 (4) ◽  
pp. 723-729
Author(s):  
Michaela Shishmanova-Doseva ◽  
Jana Tchekalarova ◽  
Zlatina Nenchovska ◽  
Natasha Ivanova ◽  
Katerina Georgieva ◽  
...  

Introduction: Epilepsy and antiepileptic drugs can affect negatively the cognitive abilities of patients. Aim: The present study aimed to evaluate the effect of topiramate (TPM) and lacosamide (LCM) on the emotional and cognitive re-sponses in naive animals and in animals with pilocarpine-induced status epilepticus.  Materials and methods: Male Wistar rats were randomly divided into 6 groups and status epilepticus was evoked in half of them by a single i.p. administration of pilocarpine (Pilo) (320 mg/kg): Pilo-veh, Pilo-TPM (80 mg/kg) and Pilo-LCM (30 mg/kg). Matched naive rats were treated with the same doses as follows: C-veh, C-TPM, and C-LCM. In a step-down passive avoidance test, the learning session was held for one day, the early retention test was conducted on day 2, and the long-term memory test - on day 7. Motor activity and anxiety were evaluated in an open field test.  Results: The Pilo-TPM and Pilo-LCM groups increased the time spent on the platform compared to Pilo-veh animals while the C-LCM animals decreased the time compared to C-veh animals during short- and long-term memory retention tests. TPM and LCM exerted an anxiolytic effect in naive rats. The two antiepileptic drugs were unable to alleviate the hyperactivity, but they alleviated the impulsivity associated with decreased anxiety level in epileptic rats. Conclusions: Our findings suggest that LCM and TPM have a beneficial effect on cognition both in naive and epileptic rats. While the two antiepileptic drugs can produce an anxiolytic effect in naive rats, they alleviate the impulsivity after pilocarpine treatment.


Author(s):  
Tokareva N.G. ◽  
Ignatieva O.I.

In the presented review of the literature, the most significant problems of modern pharmacotherapy of status epilepticus are indicated. The urgency of treatment of status epilepticus is confirmed by its frequency and ineffectiveness of traditional drugs (benzodiazepines, hydantoins, barbiturates), which have a number of side effects from the cardiovascular and respiratory systems. In Russian intensive care medicine, treatment of status epilepticus is carried out in accordance with international standards and recommendations. For a number of years, the injectable form of valproate has proven its effectiveness, including in pediatric practice. In comparative studies, phenytoin, valproate and levetiracetam are safe and equally effective in treating status epilepticus. A particular difficulty in therapy is caused by benzodiapine-resistant status epilepticus and refractory, which requires consideration of the possibility of using a combination of antiepileptic drugs. The review of foreign and domestic sources presents the results of clinical studies that allow the use of new antiepileptic drugs, which can effectively stop status epilepticus already in the early stages. New antiepileptic drugs are especially relevant in the treatment of patients refractory to drug treatment. However, treatment with antiepileptic drugs does not always show its effectiveness in refractory and super-refractory status epilepticus, which requires new approaches in complex treatment. The tolerance of drugs and the frequency of side effects are important for patients, since most of them require long-term combined use. Correct selection of antiepileptic drugs increases the level of compliance. A special approach requires the treatment of status epilepticus in the context of palliative care and comorbid pathology. In the treatment and prevention of status epilepticus, surgical treatment and the use of a ketogenic diet can be considered.


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