Risk of seizure recurrence from antiepileptic drug withdrawal among seizure-free patients for more than two years

Li, Yinchao; Chen, Shuda; Qin, Jiaming; She, Yingfang; Chen, Ying; Liu, Xianyue; Yu, Hang; Zhou, Liemin

doi:10.1016/j.yebeh.2020.107485

Cited by 7 publications

(9 citation statements)

References 37 publications

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“…The current work presents long‐term follow‐up data of an Italian cohort of adult patients with epilepsy who discontinued their AEDs. The frequency of relapses is consistent with previous studies where the range of seizure recurrence was 12%‐67% 2,12,13,20,21,30,31 . In particular, in two other external validation papers on LPM, 59% 20 and 44%, 21 respectively, of patients relapsed.…”

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

“…The frequency of relapses is consistent with previous studies where the range of seizure recurrence was 12%-67%. 2,12,13,20,21,30,31 In particular, in two other external validation papers on LPM, 59% 20 and 44%, 21 respectively, of patients relapsed. The risk factors evaluated were the same reported in the previous papers, and definitions of these variables are consistent with them.…”

Section: Discussionmentioning

confidence: 99%

“…This result is coherent with some previous reports, 1 , 14 , 27 whereas others showed either different cut‐offs (5 or 3 years) or progressive reduction of risk without giving any definite cut‐off value. 2 , 24 , 31 Therefore, until more evidence is gathered, it seems important that future studies include patients with different duration of seizure‐free period on therapy.…”

Section: Discussionmentioning

confidence: 99%

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Prediction of seizure recurrence risk following discontinuation of antiepileptic drugs

et al. 2021

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Objective Discontinuation of antiepileptic drugs (AEDs) in seizure‐free patients is an important goal because of possible long‐term side effects and the social stigma burden of epilepsy. The purpose of this work was to assess seizure recurrence risk after suspension of AEDs, to evaluate predictors for recurrence, and to investigate the recovery of seizure control after relapse. In addition, the accuracy of a previously published prediction model of seizure recurrence risk was estimated. Methods Seizure‐free patients with epilepsy who had discontinued AEDs were retrospectively enrolled. The frequency of seizure relapses after AED withdrawal as well as prognosis after recurrence were assessed and the predictive role of baseline clinical‐demographic variables was evaluated. The aforementioned prediction model was also validated and its accuracy assessed at different seizure‐relapse probability levels. Results The enrolled patients (n = 133) had been followed for a median of 3 years (range 0.8–33 years) after AED discontinuation; 60 (45%) of them relapsed. Previous febrile seizures in childhood (hazard ratio [HR] 3.927; 95% confidence interval [CI] 1.403–10.988), a seizure‐free period on therapy of less than 2 years (HR 2.313; 95% CI 1.193–4.486), and persistent motor deficits (HR 4.568; 95% CI 1.412–14.772) were the clinical features associated with relapse risk in univariate analysis. Among these variables, only a seizure‐free period on therapy of less than 2 years was associated with seizure recurrence in multivariate analysis (HR 2.365; 95% CI 1.178–4.7444). Pharmacological control of epilepsy was restored in 82.4% of the patients who relapsed. In this population, the aforementioned prediction model showed an unsatisfactory accuracy. Significance A period of freedom from seizure on therapy of less than 2 years was the main predictor of seizure recurrence. The accuracy of the previously described prediction tool was low in this cohort, thus suggesting its cautious use in real‐world clinical practice.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prediction of seizure recurrence risk following discontinuation of antiepileptic drugs

et al. 2021

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“…In the individual patient, risk factors for seizure recurrence such as younger age at onset of epilepsy, a shorter period of remission, longer duration of active epilepsy, high seizure frequency before seizure remission, ASM polytherapy, and results of the electroencephalogram might be taken into consideration, but do not preclude ASM withdrawal [47][48][49][50][51]. Some of these, and additional factors are included in the online Epilepsy Prediction Tool, designed to estimate the two-and five-year seizure recurrence risk as well as the ten-year chance of seizure freedom based on a study by Lamberink et al [49,52].…”

Section: Epilepsymentioning

confidence: 99%

The sense of stopping migraine prophylaxis

et al. 2023

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Introduction Migraine prophylactic therapy has changed over recent years with the development and approval of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway. As new therapies emerged, leading headache societies have been providing guidelines on the initiation and escalation of such therapies. However, there is a lack of robust evidence looking at the duration of successful prophylaxis and the effects of therapy discontinuation. In this narrative review we explore both the biological and clinical rationale for prophylactic therapy discontinuation to provide a basis for clinical decision-making. Methods Three different literature search strategies were conducted for this narrative review. These include i) stopping rules in comorbidities of migraine in which overlapping preventives are prescribed, notably depression and epilepsy; ii) stopping rules of oral treatment and botox; iii) stopping rules of antibodies targeting the CGRP (receptor). Keywords were utilized in the following databases: Embase, Medline ALL, Web of Science Core collection, Cochran Central Register of Controlled Trials, and Google Scholar. Discussion Reasons to guide decision-making in stopping prophylactic migraine therapies include adverse events, efficacy failure, drug holiday following long-term administration, and patient-specific reasons. Certain guidelines contain both positive and negative stopping rules. Following withdrawal of migraine prophylaxis, migraine burden may return to pre-treatment level, remain unchanged, or lie somewhere in-between. The current suggestion to discontinue CGRP(-receptor) targeted mAbs after 6 to 12 months is based on expert opinion, as opposed to robust scientific evidence. Current guidelines advise the clinician to assess the success of CGRP(-receptor) targeted mAbs after three months. Based on excellent tolerability data and the absence of scientific data, we propose if no other reasons apply, to stop the use of mAbs when the number of migraine days decreases to four or fewer migraine days per month. There is a higher likelihood of developing side effects with oral migraine preventatives, and so we suggest stopping these drugs according to the national guidelines if they are well tolerated. Conclusion Translational and basic studies are warranted to investigate the long-term effects of a preventive drug after its discontinuation, starting from what is known about the biology of migraine. In addition, observational studies and, eventually, clinical trials focusing on the effect of discontinuation of migraine prophylactic therapies, are essential to substantiate evidence-based recommendations on stopping rules for both oral preventives and CGRP(-receptor) targeted therapies in migraine. Graphical Abstract

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Long‐term effectiveness and seizure recurrence risk factors of ketogenic diet for pediatric refractory epilepsy: Experience from a tertiary care center in China

Zhang,

Li,

et al. 2023

Epileptic Disorders

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ObjectiveThis study aimed to assess the long‐term effectiveness and seizure recurrence risk in children with drug‐resistant epilepsy who achieved seizure freedom on a ketogenic diet (KD). Predictors associated with seizure recurrence were also evaluated.MethodsPatients with drug‐resistant epilepsy who received KD therapy for at least three months between May 2011 and April 2020 were included. The clinical efficacy of the KD was evaluated. Patients who achieved seizure freedom for at least three months on the KD were focused. Multivariate Cox regression models were used to explore the risk factors of seizure relapse in patients who achieved seizure freedom.ResultsThis study included 288 patients (163 males, 125 females). The seizure‐free rates of the KD at 3, 6, 12, and 24 months were 9.7%, 16.7%, 14.2%, and 9.0%, respectively. Additionally, the seizure reduction rates between 50% and 99% were 46.5%, 39.9%, 30.2%, and 20.5%, respectively. Patients with Angelman syndrome (AS) showed the highest efficacy rate, followed by those with Dravet syndrome (DS). Fifty‐one patients achieved at least three months of seizure freedom on the KD. Seizures recurred in 24 (47.1%) patients. None of the patients with AS relapsed, while those with DS had the highest recurrence rate. The etiology of epilepsy, KD maintenance treatment period, and electroencephalography (EEG) abnormalities during follow‐up differed significantly between patients with and without recurrence. However, multivariate Cox regression analysis indicated that a KD maintenance treatment period of less than 12 months and the presence of EEG abnormalities during follow‐up were significantly correlated with a higher risk of relapse. Epilepsy control was restored in 3 of the 24 (12.5%) patients who experienced relapse.SignificanceKD appears to be effective in children with various types of drug‐resistant epilepsy. A short KD maintenance treatment period and EEG abnormalities during follow‐up were associated with an increased risk of seizure recurrence.

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Risk of seizure recurrence from antiepileptic drug withdrawal among seizure-free patients for more than two years

Cited by 7 publications

References 37 publications

Prediction of seizure recurrence risk following discontinuation of antiepileptic drugs

Prediction of seizure recurrence risk following discontinuation of antiepileptic drugs

The sense of stopping migraine prophylaxis

Long‐term effectiveness and seizure recurrence risk factors of ketogenic diet for pediatric refractory epilepsy: Experience from a tertiary care center in China

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