Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy

French, Jacqueline; Abou‐Khalil, Bassel; Leroy, Robert; Yacubian, Elza Márcia Targas; Shin, Paul; Hall, Susan T.; Mansbach, Hank; Nohria, Virinder

doi:10.1212/wnl.0b013e3182194bd3

Cited by 167 publications

(216 citation statements)

References 33 publications

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“…6,8,22 Efficacy Ezogabine has been evaluated for efficacy as adjunctive therapy in partial-onset seizures in 3 multicenter, randomized, double-blind, placebo-controlled trials in 1239 adult patients. 7,[22][23][24] The primary end point was percent change in seizure frequency from baseline. Enrolled patients experienced a minimum of 4 partial seizures per month despite use of up to 3 AEDs or vagus nerve stimulation.…”

Section: Ezogabinementioning

confidence: 99%

“…Compared with placebo, ezogabine reduced seizure frequency at 600 mg/d by 27%, 900 mg/d by 25%, and 1200 mg/d by 24%. 7,[22][23][24] …”

Section: Ezogabinementioning

confidence: 99%

“…4,[22][23][24] Urinary retention was reported in approximately 2% of patients treated with ezogabine in epilepsy trials. 22 Half of the patients with retention required catheterization.…”

Section: Adverse Effectsmentioning

confidence: 99%

“…22 Neuropsychiatric symptoms, such as psychotic states associated with confusion and hallucinations, are frequently noted in patients taking ezogabine. [22][23][24] Most psychiatric symptoms resolved rapidly after discontinuation of drug use. Rapid titration at greater than the recommended doses appears to increase the risk of these adverse effects.…”

Section: Adverse Effectsmentioning

confidence: 99%

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Antiepileptic Drugs 2012: Recent Advances and Trends

Sirven

Noe

Hoerth

et al. 2012

Mayo Clinic Proceedings

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There are now 24 antiepileptic drugs (AEDs) approved for use in epilepsy in the United States by the Food and Drug Administration. A literature search was conducted using PubMed, MEDLINE, and Google for all English-language articles that discuss newly approved AEDs and the use of AEDs in epilepsy in the United States from January 1, 2008, through December 31, 2011. Five new agents were identified that have come onto the market within the past 2 years. Moreover, 3 trends involving AEDs have become clinically important and must be considered by all who treat patients with epilepsy. These trends include issues of generic substitution of AEDs, pharmacogenomics predicting serious adverse events in certain ethnic populations, and the issue of the suicide risk involving the entire class of AEDs. This article discusses the most recent AEDs approved for use in the United States and the 3 important trends shaping the modern medical management of epilepsy.

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Section: Ezogabinementioning

confidence: 99%

“…Compared with placebo, ezogabine reduced seizure frequency at 600 mg/d by 27%, 900 mg/d by 25%, and 1200 mg/d by 24%. 7,[22][23][24] …”

Section: Ezogabinementioning

confidence: 99%

“…4,[22][23][24] Urinary retention was reported in approximately 2% of patients treated with ezogabine in epilepsy trials. 22 Half of the patients with retention required catheterization.…”

Section: Adverse Effectsmentioning

confidence: 99%

Section: Adverse Effectsmentioning

confidence: 99%

See 2 more Smart Citations

Antiepileptic Drugs 2012: Recent Advances and Trends

Sirven

Noe

Hoerth

et al. 2012

Mayo Clinic Proceedings

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“…A third trial, enrolling mostly in the US, was recently reported (18). All three multicenter trials had a classical add-on design.…”

Section: Efficacymentioning

confidence: 99%

Ezogabine: A New Angle on Potassium Gates

Faught

2011

Epilepsy Curr

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Suicidality Risk of Newer Antiseizure Medications

et al. 2021

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IMPORTANCE Most antiseizure medications (ASMs) carry a US Food and Drug Administration-mandated class label warning of increased suicidality risk, based on a meta-analysis comparing suicidality between individuals treated with medications vs placebo in randomized clinical trials done before 2008. ASMs approved since then carry this warning although they were not similarly studied.OBJECTIVE To review all placebo-controlled phase 2 and 3 studies of 10 ASMs approved since 2008 to evaluate the risk of suicidality of these drugs compared with placebo.DATA SOURCES Primary publications and secondary safety analyses in PubMed of all phase 2 and 3 randomized placebo-controlled epilepsy trials of ASMs approved since 2008, using keywords epilepsy, antiepileptic drugs, seizures, suicidality, suicidal ideation, and the names of individual drugs.STUDY SELECTION All phase 2 and 3 randomized clinical trials of adjunctive treatment of drug-resistant epilepsy and their secondary safety analyses.DATA EXTRACTION AND SYNTHESIS Articles were reviewed for frequency of suicidality (ideation, attempts, and completed suicides). Mode of suicidality ascertainment included treatment-emergent adverse event reports, Standardized Medical Dictionary for Regulatory Activities queries for events in prespecified categories including suicidal ideation and behavior, prospective collection of suicidality data as a prespecified safety outcome using the Columbia-Suicide Severity Rating Scale, and retrospective evaluation by blinded review using the Columbia-Classification Algorithm of Suicide Assessment. A meta-analysis compared risk for drugs vs placebo of each outcome for all drugs overall and by individual drugs and trials.MAIN OUTCOMES AND MEASURES Suicidality (total and by ideation), attempts, and completed suicides.RESULTS Excluding studies that did not evaluate suicidality (everolimus and fenfluramine) or did not evaluate it prospectively (lacosamide, ezogabine, and clobazam), 5 drugs were analyzed: eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate. Suicidality was evaluated in 17 randomized clinical trials of these drugs, involving 5996 patients, of whom 4000 patients were treated with ASMs and 1996 with placebo. There was no evidence of increased risk of suicidal ideation (drugs vs placebo overall risk ratio, 0.75; 95% CI, 0.35-1.60) or attempt (risk ratio, 0.75; 95% CI, 0.30-1.87) overall or for any individual drug. Suicidal ideation occurred in 12 of 4000 patients treated with ASMs (0.30%) vs 7 of 1996 patients treated with placebo (0.35%) (P = .74). Three patients treated with ASMs and no patients treated with placebo attempted suicide (P = .22). There were no completed suicides.CONCLUSIONS AND RELEVANCE There is no current evidence that the 5 ASMs evaluated in this study increase suicidality in epilepsy and merit a suicidality class warning.

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Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy

Abstract: This study provides Class II evidence that EZG(RTG) 1,200 mg/day is effective as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization.

Cited by 167 publications

References 33 publications

Antiepileptic Drugs 2012: Recent Advances and Trends

Antiepileptic Drugs 2012: Recent Advances and Trends

Ezogabine: A New Angle on Potassium Gates

Suicidality Risk of Newer Antiseizure Medications

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