Tuesday, February 13, 2018

Efficacy of rapid and slow withdrawal of antiepileptic drugs during long-term video-EEG monitoring

Kumar S, Ramanujam B, Chandra PS, Dash D, Mehta S, Anubha S, Appukutan R, Rana MK, Tripathi M. Randomized controlled study comparing the efficacy of rapid and slow withdrawal of antiepileptic drugs during long-term video-EEG monitoring. Epilepsia. 2018 Feb;59(2):460-467.


Antiepileptic drugs (AEDs) are routinely withdrawn during long-term video-electroencephalography (EEG) monitoring (LTM), to record sufficient number of seizures. The efficacy of rapid and slow AED taper has never been compared in a randomized control trial (RCT), which was the objective of this study.

In this open-label RCT, patients aged 2-80 years with drug-resistant epilepsy (DRE) were randomly assigned (1:1) to rapid and slow AED taper groups. Outcome assessor was blinded to the allocation arms. Daily AED dose reduction was 30% to 50% and 15% to <30% in the rapid and slow taper groups, respectively. The primary outcome was difference in mean duration of LTM between the rapid and slow AED taper groups. Secondary outcomes included diagnostic yield, secondary generalized tonic-clonic seizure (GTCS), 4- and 24- hour seizure clusters, status epilepticus, and need for midazolam rescue treatment. The study was registered with Clinical Trial Registry-India (CTRI/2016/08/007207).

One hundred forty patients were randomly assigned to rapid (n = 70) or slow taper groups (n = 70), between June 13, 2016 and February 20, 2017. The difference in mean LTM duration between the rapid and slow taper groups was -1.8 days (95% confidence interval [CI] -2.9 to -0.8, P = .0006). Of the secondary outcome measures, time to first seizure (2.9 ± 1.7 and 4.6 ± 3.0 days in the rapid and slow taper groups respectively, P = .0002) and occurrence of 4-hour seizure clusters (11.9% and 2.9% in the rapid and slow taper groups, respectively, P = .04) were statistically significant. None of the other safety variables were different between the 2 groups. LTM diagnostic yield was 95.7% and 97.1%, in rapid and slow taper groups respectively (P = .46).

Rapid AED tapering has the advantage of significantly reducing LTM duration over slow tapering, without any serious adverse events.

Shortening the duration of video-EEG monitoring would “contribute to patient compliance and comfort with the procedure and also can ensure that more patients get in earlier for the evaluation,” Dr. Tripathi said. Independent experts speaking with Neurology Today agreed, adding that reducing the duration of video-EEG would have positive implications for the length of hospital stays and for health care costs.

The study, which enrolled 140 patients with drug-resistant epilepsy, compared two rates of AED tapering – a daily reduction of 30 to 50 percent in the rapid group, and of 15 to 30 percent in the slow group – tapering by one AED at a time in both groups. Rapid tapering reduced the duration of video-EEG by almost two days, and did not increase the risk status epilepticus, a major safety concern.

The findings should “give clinicians a confidence in tapering anticonvulsants rapidly without and significant adverse events, especially if the patient does not want to stay longer,” Dr. Tripathi said…
This was a very nicely designed study,” said Imad Najm, MD, director of Cleveland Clinic's Epilepsy Center at the Cleveland Clinic Neurological Institute, in an interview with Neurology Today. “It showed a decrease in stay of 1.8 days in the faster taper group of patients. That is very significant as a decrease in the hospital stay leads to an increased ability to accommodate more patients in the limited number of beds in the epilepsy units and a decrease in the overall costs of care.”

“They looked at multiple parameters,” Dr. Najm said. In addition to examining the differential effects of a fast and slow taper, he noted, the study was also “designed to answer the question, ‘Are we achieving the overall goal of evaluation, which is to capture seizures?’” Several secondary parameters were promising, as well, he noted. “When it comes to capturing a seizure, in 96 to 97 percent of patients, they achieved this goal. And second, when it comes to, how fast are we capturing seizures? Here, it took almost 1.7 days to get a first seizure in the fast taper group.” That is a promising outcome, he said…

“This was a well done and reasonably sized study,” agreed Kimford Meador, MD, PhD, FAAN, professor of neurology and neurosciences at Stanford University and clinical director of the Stanford Comprehensive Epilepsy Center. “For epilepsy centers that have concerns about the speed of tapering AEDs during inpatient admissions, it provides evidence to say, you can proceed at this speed safely, and you can probably go even faster.”

However, he noted, “What they call fast I don't think is particularly fast. We [at Stanford] actually go faster than their fast. They tapered one drug at time, at a rate of 30 to 50 percent per day in the rapid taper group; we do more than one drug at time, and faster than that. They might try a faster titration rate in the future,” he said.

Also, Dr. Meador noted, there are still several conditions where a clinician may decide to taper slowly. These include patient with a history of status epilepticus, postictal psychosis; patients who have their convulsive seizures controlled by AEDs, but are still having another kind of smaller attack; patients who are already having very frequent seizures on AEDs; and patients that frequently have seizures that rapidly generalize.


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