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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