Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs

Chen, Zhibin; Brodie, Martin J.; Liew, Danny; Kwan, Patrick

doi:10.1001/jamaneurol.2017.3949

Cited by 1,052 publications

(955 citation statements)

References 24 publications

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“…14,15 However, the seizure freedom rate in this analysis was comparable to the rate observed (68%) in the analysis on the same expanding cohort conducted in 2012. Patients were followed up at a single epilepsy center over a 30-year period.…”

Section: Discussionsupporting

confidence: 78%

Pharmacological outcomes in teenagers with newly diagnosed epilepsy: A 30‐year cohort study

Alsfouk

Chen

et al. 2019

Epilepsia

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Objective To evaluate the long‐term pharmacological outcomes in teenagers with different epilepsies. Method This study included teenagers aged 13‐19 years at treatment initiation who were newly treated with antiepileptic drugs (AEDs) at the epilepsy unit of the Western Infirmary in Glasgow, Scotland, between 1 September 1982 and 30 September 2012. Patients were prospectively followed until 30 April 2016, or death, with at least a 2‐year follow‐up. Results A total of 332 adolescent patients (53% female; median age 16 years; 54% with generalized epilepsy) were included. At the end of the study, 221 patients (67%) were seizure‐free. A higher seizure‐free rate was observed in those with generalized compared to focal epilepsy (72% versus 60%, P = 0.01). During the study, 108 patients had relapses after periods of being seizure‐free, most commonly due to poor adherence to AEDs (49%, n = 53/108). AED withdrawal was associated with a high risk of seizure recurrence (70%, n = 26/37), but 56% (n = 61/108) of relapsed patients became seizure‐free again by the end of the study, with only 9% (n = 31/332) meeting the International League Against Epilepsy (ILAE) definition of pharmacoresistance during follow‐up. Of the 221 seizure‐free patients, 83% achieved this on monotherapy. There was no significant difference in efficacy rate between new and standard AED monotherapy (74% versus 77%, P = 0.66). The overall poor tolerability rate of AEDs was 21% (n = 69/332). Among the different new and standard AEDs used as initial monotherapy, lamotrigine was associated with the lowest rate of adverse effects (12%, n = 15/124), while topiramate was associated with the highest rate (56%, n = 5/9). Significance Teenagers with epilepsy showed good seizure control, particularly those with generalized epilepsy. However, relapse was common and there was high risk of seizure recurrence after treatment withdrawal. Most patients were controlled on monotherapy. As the efficacy of AEDs was comparable, tolerability can be a primary consideration for AED selection in this population.

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Section: Discussionsupporting

confidence: 78%

Pharmacological outcomes in teenagers with newly diagnosed epilepsy: A 30‐year cohort study

Alsfouk

Chen

et al. 2019

Epilepsia

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“…20 An obvious weakness of our study is its retrospective design: We could not account for possible effects of the natural history of JME on outcomes. 23 The ILAE definition of treatment failure is lack of seizure freedom after an informative trial of an intervention 17 ; for clinical utility, we defined failure as less than 50% reduction in seizure frequency. 21 Individuals with refractory epilepsy may, however, be overrepresented in our sample.…”

Section: Discussionmentioning

confidence: 99%

Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy

et al. 2019

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Objective To study the effectiveness and tolerability of antiepileptic drugs (AEDs) commonly used in juvenile myoclonic epilepsy (JME). Methods People with JME were identified from a large database of individuals with epilepsy, which includes detailed retrospective information on AED use. We assessed secular changes in AED use and calculated rates of response (12‐month seizure freedom) and adverse drug reactions (ADRs) for the five most common AEDs. Retention was modeled with a Cox proportional hazards model. We compared valproate use between males and females. Results We included 305 people with 688 AED trials of valproate, lamotrigine, levetiracetam, carbamazepine, and topiramate. Valproate and carbamazepine were most often prescribed as the first AED. The response rate to valproate was highest among the five AEDs (42.7%), and significantly higher than response rates for lamotrigine, carbamazepine, and topiramate; the difference to the response rate to levetiracetam (37.1%) was not significant. The rates of ADRs were highest for topiramate (45.5%) and valproate (37.5%). Commonest ADRs included weight change, lethargy, and tremor. In the Cox proportional hazards model, later start year (1.10 [1.08‐1.13], P < 0.001) and female sex (1.41 [1.07‐1.85], P = 0.02) were associated with shorter trial duration. Valproate was associated with the longest treatment duration; trials with carbamazepine and topiramate were significantly shorter (HR [CI]: 3.29 [2.15‐5.02], P < 0.001 and 1.93 [1.31‐2.86], P < 0.001). The relative frequency of valproate trials shows a decreasing trend since 2003 while there is an increasing trend for levetiracetam. Fewer females than males received valproate (76.2% vs 92.6%, P = 0.001). Significance In people with JME, valproate is an effective AED; levetiracetam emerged as an alternative. Valproate is now contraindicated in women of childbearing potential without special precautions. With appropriate selection and safeguards in place, valproate should remain available as a therapy, including as an alternative for women of childbearing potential whose seizures are resistant to other treatments.

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“…1 One in 26 Americans will develop epilepsy sometime in their life. 3 These patients are at high risk for sudden unexpected death in epilepsy (SUDEP), the leading cause of death in patients with refractory epilepsy. 3 These patients are at high risk for sudden unexpected death in epilepsy (SUDEP), the leading cause of death in patients with refractory epilepsy.…”

Section: Introductionmentioning

confidence: 99%

Effect of monoamine reuptake inhibition and α₁ blockade on respiratory arrest and death following electroshock‐induced seizures in mice

et al. 2019

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Summary Objective Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. Although the mechanisms for SUDEP are incompletely understood, seizure‐induced respiratory arrest (S‐IRA) has been strongly and consistently implicated. A body of evidence indicates that serotonin (5‐HT), a modulator of breathing, plays a critical role in SUDEP. Because the 5‐HT and norepinephrine (NE) systems interact in many biologic processes and NE is known to modulate breathing and seizures, we hypothesized that NE may play a role in S‐IRA and SUDEP. Methods We examined the effects of pharmacologic manipulation of 5‐HT and NE on S‐IRA and death following maximal electroshock (MES)–induced seizures in adult wild‐type (WT) mice, genetically 5‐HT neuron–deficient (Lmx1bf/f/p) mice, and chemically NE neuron–deficient mice. Mice were treated with pharmacologic agents targeting the serotonergic and noradrenergic systems and subjected to seizure induction via MES while breathing was measured via whole‐body plethysmography. Results S‐IRA and death was reduced in WT mice with NE reuptake inhibitors (NRIs), reboxetine and atomoxetine, selective serotonin reuptake inhibitors (SSRIs), fluoxetine and citalopram, and the dual 5‐HT/NE reuptake inhibitor (SNRI), duloxetine. S‐IRA and death was also reduced in Lmx1bf/f/p mice with reboxetine and fluoxetine. The protective effects of the reuptake inhibitors were prevented by the α1 antagonist, prazosin. Citalopram did not reduce S‐IRA and death in NE neuron–deficient mice. Significance These data suggest that 5‐HT and NE critically interact in the modulation of breathing following a seizure and potentially inform preventive strategies for SUDEP.

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Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs

Cited by 1,052 publications

References 24 publications

Pharmacological outcomes in teenagers with newly diagnosed epilepsy: A 30‐year cohort study

Pharmacological outcomes in teenagers with newly diagnosed epilepsy: A 30‐year cohort study

Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy

Effect of monoamine reuptake inhibition and α₁ blockade on respiratory arrest and death following electroshock‐induced seizures in mice

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Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs

Cited by 1,052 publications

References 24 publications

Pharmacological outcomes in teenagers with newly diagnosed epilepsy: A 30‐year cohort study

Pharmacological outcomes in teenagers with newly diagnosed epilepsy: A 30‐year cohort study

Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy

Effect of monoamine reuptake inhibition and α1 blockade on respiratory arrest and death following electroshock‐induced seizures in mice

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Product

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Effect of monoamine reuptake inhibition and α₁ blockade on respiratory arrest and death following electroshock‐induced seizures in mice