Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data

Nevitt, Sarah J; Sudell, Maria; Weston, Jennifer; Smith, Catrin Tudur; Marson, Anthony G

doi:10.1002/14651858.cd011412.pub2

Cited by 89 publications

(110 citation statements)

References 165 publications

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“…10,29,30 The second most common reason for neurologists not recommending ASM therapy at diagnosis was that further investigation results were required to characterize the epilepsy, which can enhance diagnostic certainty and influence ASM choice. 31 These are clearly reasoned, literature-supported decisions and do not necessarily represent a deficiency in management, although there is a paucity of evidence regarding the outcomes of deferred treatment in patients who are newly diagnosed with epilepsy, particularly in those with a single seizure who meet the new diagnostic criteria for epilepsy.…”

Section: Discussionmentioning

confidence: 99%

Treatment initiation decisions in newly diagnosed epilepsy–A longitudinal cohort study

et al. 2020

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Objective To examine the factors and reasons influencing treatment initiation decisions in patients with newly diagnosed epilepsy. Methods We assessed antiseizure medication initiation decisions in adults with newly diagnosed epilepsy seen at first seizure clinics in Western Australia between 1999 and 2016 and followed to 2018. Results Of 610 patients (median age 40 years, 61.0% male), 426 (69.8%) were diagnosed after two or more seizures and 184 (30.2%) after a single seizure with risk factors for recurrence. Treatment was commenced in 427 patients (70.0%) at diagnosis, 112 (18.4%) during follow‐up, mostly after further seizures, whereas 71 (11.6%) remained untreated at last follow‐up. Elders (≥65 years, odds ratio [OR] = 3.06, 95% confidence interval [CI]: 1.62‐5.80), more seizures (OR = 3.48, 95% CI: 2.03‐5.96), and epileptogenic lesions on neuroimaging (OR = 2.15, 95% CI: 1.26‐3.68) had a higher likelihood of treatment at diagnosis. Patients with less than one seizure per year within the preceding year (OR = 0.40, 95% CI: 0.21‐0.73) and of higher socioeconomic status (OR = 0.985, 95% CI: 0.977‐0.994) were less likely to be treated. For 93 patients (15.2%), treatment was not recommended at diagnosis, most commonly because only a single seizure had occurred. Ninety patients (14.8%) declined recommended treatment, mostly because they were unconvinced of the need for treatment or the diagnosis. Significance Thirty percent of adults with newly diagnosed epilepsy were not immediately treated. Treatment initiation in this real‐world cohort was influenced by age, number of seizures prior to diagnosis, imaging findings, patient preferences, and socioeconomic status.

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Section: Discussionmentioning

confidence: 99%

Treatment initiation decisions in newly diagnosed epilepsy–A longitudinal cohort study

et al. 2020

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“…For both AEDs, rates of ADRs were similar to those observed in SANAD. 13,32 The commonest ADR to levetiracetam was behavioral disorder, and indeed concerns have been previously raised about the neuropsychiatric side effects of levetiracetam and topiramate in people with JME, 33 in whom psychiatric comorbidities and impulsive personality traits appear overrepresented. 31 Due to the retrospective nature of our study, some types of ADRs may have been more frequently recorded than others.…”

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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“…Individual-level meta-analyses also allow to reinstate patients or include follow-up data that were excluded from published analyses; TA B L E 4 Tolerability of antiepileptic drugs in newly diagnosed focal epilepsy however, the likelihood to not obtain suitable data from all relevant studies is high and can lead to bias. 33 Recently, an individual-level NMA of AED monotherapy for epilepsy 34…”

Section: Discussionmentioning

confidence: 99%

“…TA B L E 4 Tolerability of antiepileptic drugs in newly diagnosed focal epilepsy however, the likelihood to not obtain suitable data from all relevant studies is high and can lead to bias 33. Recently, an individual-level NMA of AED monotherapy for epilepsy34 indicated CBZ and LMT as suitable first-line treatments for individuals with partial onset seizures and LEV as a valid alternative. These conclusions were derived from the analyses of time-based endpoints; indeed, the primary outcome was the time to withdrawal of allocated treatment, and secondary outcomes included the times to achieve 12-month remission, 6-month remission, and first seizure post-randomization.…”

mentioning

confidence: 99%

Antiepileptic monotherapy in newly diagnosed focal epilepsy. A network meta-analysis

Lattanzi

Zaccara²,

Giovannelli

et al. 2018

Acta Neurol Scand

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Second and third generation AEDs have been directly compared to controlled-release carbamazepine (CBZ-CR) as initial monotherapy for new-onset focal epilepsy. Conversely, no head-to-head trials have been performed. The aim of this study was to estimate the comparative efficacy and tolerability of the antiepileptic monotherapies in adults with newly diagnosed focal epilepsy through a network meta-analysis (NMA). Randomized, double-blinded, parallel group, monotherapy studies comparing any AED to CBZ-CR in adults with newly diagnosed untreated epilepsy with focal-onset seizures was identified. The outcome measures were the seizure freedom for 6 and 12 months, the occurrence of treatment-emergent adverse events (TEAEs), and the treatment withdrawal due to TEAEs. Mixed treatment comparisons were conducted by a Bayesian NMA using the Markov chain Monte Carlo methods. Effect sizes were calculated as odds ratios (ORs) with 95% credible intervals (CrIs). Four trials were included involving 2856 participants, 1445 for CBZ-CR and 1411 for the comparative AEDs. Monotherapy AEDs compared to CBR-CR were levetiracetam (LEV), zonisamide (ZNS), lacosamide (LCM), and eslicarbazepine acetate (ESL). There were no statistical differences in the 6- and 12-month seizure freedom and TEAEs occurrence between LEV, ZNS, LCM, ESL, and CBZ-CR In the analysis of drug withdrawal due to TEAEs, LCM treatment was associated with a significantly lower discontinuation rate than CBZ-CR (OR 0.659, 95% CrI 0.428-0.950). LEV, ZNS, LCM, and ESL are effective initial monotherapy treatments in adult patients with newly diagnosed focal epilepsy and represent suitable alternatives to CBZ-CR.

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Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data

Cited by 89 publications

References 165 publications

Treatment initiation decisions in newly diagnosed epilepsy–A longitudinal cohort study

Treatment initiation decisions in newly diagnosed epilepsy–A longitudinal cohort study

Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy

Antiepileptic monotherapy in newly diagnosed focal epilepsy. A network meta-analysis

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