Wednesday, May 17, 2017

The efficacy of different kinds of intravenous antiepileptic drugs in the treatment of status epilepticus

Redecker J, Wittstock M, Rösche J. The efficacy of different kinds of intravenously applied antiepileptic drugs in the treatment of status epilepticus. How can it be determined? Epilepsy Behav. 2017 Apr 28;71(Pt A):35-38.

Abstract
We explored the influence of four different efficacy criteria on the results of observational studies concerning the treatment of status epilepticus (SE) and its subtypes. We compared and contrasted the results of four different efficacy criteria for the effectiveness of phenytoin, valproate, levetiracetam, and lacosamide. Criterion 1=the last antiepileptic drug (AED) administered before SE termination. Criterion 2=the last drug introduced into the antiepileptic therapy within 72h before the cessation of SE and without changes in dosage or number of the co-medication. Criterion 3=the last drug introduced into the antiepileptic therapy or increased in dose within 24h before termination of the SE without changes in the co-medication. Criterion 4=the last drug introduced into the antiepileptic therapy within 72h before the cessation of SE even allowing changes in the co-medication. We used two-tailed χ2-tests with the Yates adjustment for small samples to evaluate statistical differences between efficacy rates of different AEDs in the entire group and in subgroups of SE according to the second level of subdivisions in axis 1 and according to axis 2 of the new ILAE classification. A total of 145 treatment episodes in 124 patients (47 male, 77 female) were evaluated. There were 23 significant differences in efficacy according to the different criteria. Only criteria 1 and 3 led to significant results in our analysis. When incorporating theoretical considerations and the results of this study, criterion 3 seems to be the most appropriate measure for the evaluation of efficacy of an AED in the treatment of SE, because it seems to be more reasonable than criterion 1.
The aim of the study was to identify which criteria best evaluate AED efficacy in ending status epilepticus. The results have implications for future trials designed to investigate the efficacy of these drugs.
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“[C]ombining theoretical considerations and the results of this study, criterion 3 (i.e. “the last drug introduced into the antiepileptic therapy or increased in dose within 24 hours before termination of the status epilepticus without changes in the co-medication”) appears to be the most appropriate for the evaluation of efficacy of an antiepileptic drug in the treatment of status epilepticus. Further studies on the treatment of status epilepticus should use this criterion at least as one of their efficacy criteria,” wrote first author Juliane Redecker, of the University of Rostock, Germany, and colleagues.

Key Results for the overall treatment of status epilepticus:

• Large range of efficacy rates using the different criteria

• Only criteria 1 and 3 showed significant results, with comparisons of the four criteria showing 23 significant differences (P<0.001-0.05)

• Criteria 1: LEV had highest percentage of effective administrations:

LEV (52%) > LCM (37.5%) > VPA (33.9%) > PHT (16.1%)

• Criteria 2: LCM had highest percentage of effective administrations:

LCM (18.8%) > LEV (16.8%) > VPA (11.3%) > PHT (9.7%)

• Criteria 3: LEV had highest percentage of effective administrations:

LEV (36.6%) > LCM (31.3%) > VPA (24.2%) > PHT (6.5%)

• Criteria 4: LEV had highest percentage of effective administrations:

LEV (27.7%) > PHT (26.8%) > VPA (22.6%) >LCM (21.9%)

Subgroup analyses showed that efficacy may differ depending on status epilepticus subtype (convulsive, focal motor, nonconvulsive with coma, nonconvulsive without coma). Using criteria 1, for example, VPA (50%) was most effective in treating convulsive status epilepticus, followed by LEV (47.1%), LCM (25%), and PHT (20%).

The authors noted that criteria 3 seems “more reasonable” than criterion 1, which may be “questionable.” Criterion 1 identifies the termination drug as one that may have been used repeatedly over days or weeks, and may have had many ineffective administrations. 

The authors noted that criteria 3 seems “more reasonable” than criterion 1, which may be “questionable.” Criterion 1 identifies the termination drug as one that may have been used repeatedly over days or weeks, and may have had many ineffective administrations. 

The authors noted that the study could not control for the order in which AEDs were administered. LEV was mainly given in patients with established status epilepticus, while the other three AEDs were used in cases of refractory or super-refractory status epilepticus. This practice may have influenced results in favor of LEV.

Take-home Points

• A study that tested four different efficacy criteria for comparing intravenous AEDs suggested that levetiracetam is generally more effective at ending status epilepticus than valproate, phenytoin, and lacosamide.

• Subgroup analyses showed that efficacy may differ depending on status epilepticus subtype.

• The study showed that criteria 3 (the last drug introduced into AED therapy or increased in dose within 24 hours before ending status epilepticus, without changes in co-medication) may be most appropriate for evaluating efficacy of AEDs. 


http://www.neurologytimes.com/epilepsy-and-seizure/status-epilepticus-efficacy-iv-drugs

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