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The Cochrane Database of Systematic... Oct 2023Newborn infants are more prone to seizures than older children and adults. The neuronal injury caused by seizures in neonates often results in long-term... (Review)
Review
BACKGROUND
Newborn infants are more prone to seizures than older children and adults. The neuronal injury caused by seizures in neonates often results in long-term neurodevelopmental sequelae. There are several options for anti-seizure medications (ASMs) in neonates. However, the ideal choice of first-, second- and third-line ASM is still unclear. Further, many other aspects of seizure management such as whether ASMs should be initiated for only-electrographic seizures and how long to continue the ASM once seizure control is achieved are elusive.
OBJECTIVES
1. To assess whether any ASM is more or less effective than an alternative ASM (both ASMs used as first-, second- or third-line treatment) in achieving seizure control and improving neurodevelopmental outcomes in neonates with seizures. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 2. To assess maintenance therapy with ASM versus no maintenance therapy after achieving seizure control. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 3. To assess treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates.
SEARCH METHODS
We searched MEDLINE, Embase, CENTRAL, Epistemonikos and three databases in May 2022 and June 2023. These searches were not limited other than by study design to trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that included neonates with EEG-confirmed or clinically diagnosed seizures and compared (1) any ASM versus an alternative ASM, (2) maintenance therapy with ASM versus no maintenance therapy, and (3) treatment of clinical or EEG seizures versus treatment of clinical seizures alone.
DATA COLLECTION AND ANALYSIS
Two review authors assessed trial eligibility, risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence interval (CI). We used GRADE to assess the certainty of evidence.
MAIN RESULTS
We included 18 trials (1342 infants) in this review. Phenobarbital versus levetiracetam as first-line ASM in EEG-confirmed neonatal seizures (one trial) Phenobarbital is probably more effective than levetiracetam in achieving seizure control after first loading dose (RR 2.32, 95% CI 1.63 to 3.30; 106 participants; moderate-certainty evidence), and after maximal loading dose (RR 2.83, 95% CI 1.78 to 4.50; 106 participants; moderate-certainty evidence). However, we are uncertain about the effect of phenobarbital when compared to levetiracetam on mortality before discharge (RR 0.30, 95% CI 0.04 to 2.52; 106 participants; very low-certainty evidence), requirement of mechanical ventilation (RR 1.21, 95% CI 0.76 to 1.91; 106 participants; very low-certainty evidence), sedation/drowsiness (RR 1.74, 95% CI 0.68 to 4.44; 106 participants; very low-certainty evidence) and epilepsy post-discharge (RR 0.92, 95% CI 0.48 to 1.76; 106 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months. Phenobarbital versus phenytoin as first-line ASM in EEG-confirmed neonatal seizures (one trial) We are uncertain about the effect of phenobarbital versus phenytoin on achieving seizure control after maximal loading dose of ASM (RR 0.97, 95% CI 0.54 to 1.72; 59 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months. Maintenance therapy with ASM versus no maintenance therapy in clinically diagnosed neonatal seizures (two trials) We are uncertain about the effect of short-term maintenance therapy with ASM versus no maintenance therapy during the hospital stay (but discontinued before discharge) on the risk of repeat seizures before hospital discharge (RR 0.76, 95% CI 0.56 to 1.01; 373 participants; very low-certainty evidence). Maintenance therapy with ASM compared to no maintenance therapy may have little or no effect on mortality before discharge (RR 0.69, 95% CI 0.39 to 1.22; 373 participants; low-certainty evidence), mortality at 18 to 24 months (RR 0.94, 95% CI 0.34 to 2.61; 111 participants; low-certainty evidence), neurodevelopmental disability at 18 to 24 months (RR 0.89, 95% CI 0.13 to 6.12; 108 participants; low-certainty evidence) and epilepsy post-discharge (RR 3.18, 95% CI 0.69 to 14.72; 126 participants; low-certainty evidence). Treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates (two trials) Treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation (MD -1871.16, 95% CI -4525.05 to 782.73; 68 participants; low-certainty evidence), mortality before discharge (RR 0.59, 95% CI 0.28 to 1.27; 68 participants; low-certainty evidence) and epilepsy post-discharge (RR 0.75, 95% CI 0.12 to 4.73; 35 participants; low-certainty evidence). The trials did not report on mortality or neurodevelopmental disability at 18 to 24 months. We report data from the most important comparisons here; readers are directed to Results and Summary of Findings tables for all comparisons.
AUTHORS' CONCLUSIONS
Phenobarbital as a first-line ASM is probably more effective than levetiracetam in achieving seizure control after the first loading dose and after the maximal loading dose of ASM (moderate-certainty evidence). Phenobarbital + bumetanide may have little or no difference in achieving seizure control when compared to phenobarbital alone (low-certainty evidence). Limited data and very low-certainty evidence preclude us from drawing any reasonable conclusion on the effect of using one ASM versus another on other short- and long-term outcomes. In neonates who achieve seizure control after the first loading dose of phenobarbital, maintenance therapy compared to no maintenance ASM may have little or no effect on all-cause mortality before discharge, mortality by 18 to 24 months, neurodevelopmental disability by 18 to 24 months and epilepsy post-discharge (low-certainty evidence). In neonates with hypoxic-ischaemic encephalopathy, treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation, all-cause mortality before discharge and epilepsy post-discharge (low-certainty evidence). All findings of this review apply only to term and late preterm neonates. We need well-designed RCTs for each of the three objectives of this review to improve the precision of the results. These RCTs should use EEG to diagnose seizures and should be adequately powered to assess long-term neurodevelopmental outcomes. We need separate RCTs evaluating the choice of ASM in preterm infants.
Topics: Infant; Child; Infant, Newborn; Adult; Humans; Adolescent; Phenytoin; Levetiracetam; Epilepsy; Phenobarbital; Seizures
PubMed: 37873971
DOI: 10.1002/14651858.CD014967.pub2 -
Neurology Jan 2023Early life epilepsies are common and often debilitating, but no evidence-based management guidelines exist outside of those for infantile spasms. We conducted a...
BACKGROUND AND OBJECTIVES
Early life epilepsies are common and often debilitating, but no evidence-based management guidelines exist outside of those for infantile spasms. We conducted a systematic review of the effectiveness and harms of pharmacologic and dietary treatments for epilepsy in children aged 1-36 months without infantile spasms.
METHODS
We searched EMBASE, MEDLINE, PubMed, and the Cochrane Library for studies published from January 1, 1999, to August 19, 2021. Using prespecified criteria, we identified studies reporting data on children aged 1-36 months receiving pharmacologic or dietary treatments for epilepsy. We did not require that studies report etiology-specific data. We excluded studies of neonates, infantile spasms, and status epilepticus. We included studies administering 1 of 29 pharmacologic treatments and/or 1 of 5 dietary treatments reporting effectiveness outcomes at ≥ 12 weeks. We reviewed the full text to find any subgroup analyses of children aged 1-36 months.
RESULTS
Twenty-three studies met inclusion criteria (6 randomized studies, 2 nonrandomized comparative studies, and 15 prestudies/poststudies). All conclusions were rated low strength of evidence. Levetiracetam leads to seizure freedom in some infants (32% and 66% in studies reporting seizure freedom), but data on 6 other medications were insufficient to permit conclusions about effectiveness (topiramate, lamotrigine, phenytoin, vigabatrin, rufinamide, and stiripentol). Three medications (levetiracetam, topiramate, and lamotrigine) were rarely discontinued because of adverse effects, and severe events were rare. For diets, the ketogenic diet leads to seizure freedom in some infants (rates 12%-37%), and both the ketogenic diet and modified Atkins diet reduce average seizure frequency, but reductions are greater with the ketogenic diet (1 RCT reported a 71% frequency reduction at 6 months for ketogenic diet vs only a 28% reduction for the modified Atkins diet). Dietary harms were not well-reported.
DISCUSSION
Little high-quality evidence exists on pharmacologic and dietary treatments for early life epilepsies. Future research should isolate how treatments contribute to outcomes, conduct etiology-specific analyses, and report patient-centered outcomes such as hospitalization, neurodevelopment, functional performance, sleep quality, and patient and caregiver quality of life.
TRIAL REGISTRATION INFORMATION
This systematic review was registered in PROSPERO (CRD42021220352) on March 5, 2021.
Topics: Infant; Infant, Newborn; Child; Humans; Lamotrigine; Levetiracetam; Topiramate; Spasms, Infantile; Quality of Life; Epilepsy; Anticonvulsants; Diet, Ketogenic
PubMed: 36270899
DOI: 10.1212/WNL.0000000000201026 -
Epilepsy & Behavior : E&B Oct 2020The objective of the study was to perform a systematic review and meta-analysis to evaluate the efficacy and safety of levetiracetam (LEV) or phenytoin (PHT) as... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
The objective of the study was to perform a systematic review and meta-analysis to evaluate the efficacy and safety of levetiracetam (LEV) or phenytoin (PHT) as second-line treatment for status epilepticus (SE).
METHODS
PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Latin American and Caribbean Health Sciences Literature (LILACS), Scopus, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and Google Scholar were assessed for prospective randomized trials comparing LEV with PHT as second-line treatment of SE published from inception until December 18th, 2019. The primary outcome was seizure cessation. Data were analyzed using a random-effects model. Quality analysis was performed using version 2 of the Cochrane risk-of-bias tool (RoB 2). The study protocol was registered on PROSPERO (CRD42020136417).
RESULTS
Nine studies with a total of 1732 patients were included. Overall, seizure cessation occurred in 657 of 887 (74%) of patients in the LEV group and 600 of 845 (71%) in the PHT group. Treatment success did not differ significantly between groups, and the relative risk (RR) was 1.05 (95% confidence interval (CI): 0.98-1.12; I = 53%). Six of the studies were at low risk of bias, one study had some risk, and two studies had high risk.
CONCLUSIONS
The use of LEV or PHT as second-line agents after benzodiazepine (BZD) for the treatment of SE was not associated with a difference in seizure cessation. Because there are minimal differences in efficacy at this time, clinicians should consider alternative factors when deciding on an antiepileptic drug (AED).
Topics: Anticonvulsants; Benzodiazepines; Drug Therapy, Combination; Humans; Levetiracetam; Phenytoin; Piracetam; Prospective Studies; Randomized Controlled Trials as Topic; Seizures; Status Epilepticus; Treatment Outcome
PubMed: 32707535
DOI: 10.1016/j.yebeh.2020.107286 -
The Cochrane Database of Systematic... Mar 2014Epilepsy is a common neurological condition characterised by recurrent seizures. Sulthiame (STM) is widely used as an antiepileptic drug in Europe and Israel. In this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epilepsy is a common neurological condition characterised by recurrent seizures. Sulthiame (STM) is widely used as an antiepileptic drug in Europe and Israel. In this review, we present a summary of evidence for the use of STM as monotherapy in epilepsy.
OBJECTIVES
To examine the efficacy and side effect profile of STM as monotherapy when compared with placebo or another antiepileptic drug.
SEARCH METHODS
We searched the Cochrane Epilepsy Group Specialised Register (24 October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), MEDLINE Ovid (1946 to 24 October 2013), SCOPUS (1823 to 24 October 2013), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal (28 October 2013) and ClinicalTrials.gov (28 October 2013). We imposed no language restrictions. We contacted the manufacturers of STM and researchers in the field to ask about ongoing and unpublished studies.
SELECTION CRITERIA
Randomised controlled monotherapy trials of STM in people of any age with epilepsy of any aetiology.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion and extracted the relevant data.The following outcomes were assessed: (1) time to treatment failure; (2) time to 12-month remission; (3) proportion seizure free at 12 months; (4) adverse effects; and (5) quality of life scoring. Primary analyses were intention-to-treat when possible. A narrative analysis of the data was presented.
MAIN RESULTS
Two studies representing 100 participants with a diagnosis of benign epilepsy of childhood with centrotemporal spikes (BECTS) and one study representing 146 participants with a diagnosis of generalised tonic-clonic seizures (GTCS) were included. STM was given as monotherapy compared with placebo in the BECTS studies and compared with phenytoin in the GTCS study. An English translation of the full text of one of the BECTS studies could not be found, and analysis of this study was based solely on the English translation of the abstract. No data were reported for outcome (1), (2), (3) or (5). Reporting of adverse effects was incomplete. Participants receiving STM were significantly less likely to develop gingival hyperplasia than were participants receiving phenytoin in the GTCS study (risk ratio (RR) 0.03, 95% confidence interval (CI) 0.00 to 0.58). No further statistically significant adverse events were noted when STM was compared with phenytoin or placebo. Two ongoing studies comparing STM monotherapy versus placebo or levetiracetam in BECTS were identified.
AUTHORS' CONCLUSIONS
Small sample size, poor methodological quality and lack of data on important outcome measures prevent any meaningful conclusions regarding the efficacy and safety of sulthiame as monotherapy in epilepsy.
Topics: Adult; Anticonvulsants; Child; Child, Preschool; Early Termination of Clinical Trials; Epilepsy; Epilepsy, Tonic-Clonic; Female; Humans; Male; Phenytoin; Randomized Controlled Trials as Topic; Thiazines
PubMed: 24609897
DOI: 10.1002/14651858.CD010062.pub2 -
International Journal of Clinical... Jul 2018Therapeutic response to phenytoin (PHT), a first-line antiepileptic drug (AED), is highly variable, in part likely due to genetic factors. Genetic polymorphisms in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Therapeutic response to phenytoin (PHT), a first-line antiepileptic drug (AED), is highly variable, in part likely due to genetic factors. Genetic polymorphisms in cytochrome P450 (CYP) 2C9 and CYP2C19 are expected to affect the metabolism of PHT and consequently affect its maintenance doses. We aimed to clarify the effects of genetic polymorphisms in both enzymes on daily PHT maintenance dosage in Asian epileptic patients by meta-analysis.
MATERIALS AND METHODS
A systematic literature search was conducted in PubMed and EMBASE for relevant studies published prior to April 14, 2017. RevMan 5.2.3 software was used to analyze the relationship between CYP2C9/2C19 polymorphisms and PHT maintenance doses.
RESULTS
A total of 6 studies with 993 patients fulfilling the inclusion criteria were included in our meta-analysis. The homozygous and heterozygous CYP2C19 mutation group (i.e., CYP2C19*2/*2, CYP2C19*3/*3, or CYP2C19*2/*3 group) required significant decrease of PHT maintenance dose. The starting maintenance dose suggested in this group is 4.38 mg/kg/day. Patients with heterozygous CYP2C9 or both heterozygous CYP2C9 and CYP2C19 showed a trend but not a statistically-significant decrease of PHT dose, but dosage adjustment was recommended.
CONCLUSION
The meta-analysis indicates that CYP2C9 and CYP2C19 polymorphisms are associated with lower PHT maintenance dosage in Asian epileptic patients. Ethnic differences can influence PHT maintenance dose. .
Topics: Anticonvulsants; Asian People; Chi-Square Distribution; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Drug Monitoring; Epilepsy; Heterozygote; Homozygote; Humans; Pharmacogenetics; Pharmacogenomic Variants; Phenytoin; Polymorphism, Single Nucleotide; Risk Factors; Treatment Outcome
PubMed: 29628024
DOI: 10.5414/CP203083 -
Journal of Tropical Pediatrics May 2021To evaluate the efficacy and safety of levetiracetam (LEV) in comparison to phenytoin (PHT) as second line antiseizure medication (ASM) for Pediatric convulsive status... (Meta-Analysis)
Meta-Analysis
Efficacy and Safety of Levetiracetam vs. Phenytoin as Second Line Antiseizure Medication for Pediatric Convulsive Status Epilepticus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
OBJECTIVE
To evaluate the efficacy and safety of levetiracetam (LEV) in comparison to phenytoin (PHT) as second line antiseizure medication (ASM) for Pediatric convulsive status epilepticus (SE).
DATA SOURCE
PubMed, Embase, Google scholar/Google, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials.
STUDY SELECTION
Randomized controlled trials (RCTs) assessing LEV and PHT as second line agent for convulsive SE in children <18 years published between 1 January 2000 and 30 November 2020.
DATA EXTRACTION
The data were pooled regarding the proportion of children achieving seizure cessation within 5-60 min of completion of study drug infusion (primary outcome); and seizure cessation within 5 min, time to achieve seizure cessation, seizure recurrence between 1 to 24 h, intubation and cardiovascular instability (secondary outcomes). Data were analyzed using RevMan version 5.4 and quality analysis was done using Cochrane risk-of-bias tool. The study protocol was registered with PROSPERO.
DATA SYNTHESIS
Twelve RCTs with 2293 children were included. Seizure cessation within 5-60 min was similar with both the drugs [82% in LEV vs. 77.5% in PHT, risk ratio (RR) = 1.04, 95% confidence interval (95% CI) 0.97-1.11, p = 0.30]. Seizure recurrences within 1-24 h was higher with PHT in comparison to LEV (16.6% vs. 9.7%, RR = 0.63, 95% CI 0.44-0.90, p = 0.01). Higher proportion of children in PHT group required intubation and mechanical ventilation (21.4% vs. 14.2%, RR = 0.54, 95% CI 0.30-0.98, p = 0.04). Seizure cessation within 5 min, time to achieve seizure cessation, and cardiovascular instability were similar with both the drugs. Three RCTs were at low risk of bias and nine were at high risk of bias.
CONCLUSION
The efficacy of LEV is similar to PHT as second line ASM for Pediatric convulsive SE. Seizure recurrences between 1 to24 h and requirement of intubation and mechanical ventilation were significantly higher with PHT in comparison to LEV.
Topics: Anticonvulsants; Child; Humans; Levetiracetam; Phenytoin; Randomized Controlled Trials as Topic; Status Epilepticus
PubMed: 34089322
DOI: 10.1093/tropej/fmab014 -
Seizure Oct 2021We systematically reviewed the existing literature on the cosmetic adverse effects of antiseizure medications (ASMs) in order to depict a clear picture of these unwanted... (Review)
Review
BACKGROUND
We systematically reviewed the existing literature on the cosmetic adverse effects of antiseizure medications (ASMs) in order to depict a clear picture of these unwanted side effects of ASMs with a particular attention to hair loss, hirsutism, acne, and gingival hyperplasia.
METHODS
This systematic review was prepared according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Scopus, MEDLINE, and Google Scholar from the inception to 25 March, 2021 were systematically searched. These key words (title/abstract) were used: "hair loss" OR "hirsutism" OR "acne" OR "gingival hyperplasia" AND "seizure" OR "epilepsy" OR "anriseizure" OR "antiepileptic". The exclusion criteria included: non-original studies, articles not in English, and animal studies.
RESULTS
The primary search yielded 3938 studies; 127 studies were related to the topic and were included in the current systematic review. The most robust evidence on cosmetic adverse effects of ASMs were related to phenytoin (causing gingival hyperplasia, hirsutism, and acne) and valproate (causing hair loss and hirsutism); however, many other ASMs were also implicated in causing these cosmetic adverse effects.
CONCLUSION
Antiseizure medications may be associated with various cosmetic adverse effects. Phenytoin and valproate are the most notorious ASMs in this regard; but, other ASMs have also been implicated in causing hair loss, hirsutism, acne, and gingival hyperplasia. Physicians should pay more attention to these significant adverse effects that may affect a patient's facial attractiveness, quality of life, and emotional state.
Topics: Animals; Anticonvulsants; Epilepsy; Humans; Phenytoin; Quality of Life; Valproic Acid
PubMed: 34052629
DOI: 10.1016/j.seizure.2021.05.010 -
The Cochrane Database of Systematic... May 2013This is an updated version of the original Cochrane review published in The Cochrane Library 2006, Issue 2.Worldwide, phenytoin is a commonly used antiepileptic drug.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in The Cochrane Library 2006, Issue 2.Worldwide, phenytoin is a commonly used antiepileptic drug. For the newer drugs such as oxcarbazepine, it is important to know how they compare with standard treatments.
OBJECTIVES
To review the best evidence comparing oxcarbazepine and phenytoin when used as monotherapy in participants with partial onset seizures or generalised tonic-clonic seizures with or without other generalised seizure types.
SEARCH METHODS
We searched the Cochrane Epilepsy Group's Specialised Register (22 January 2013), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012, Issue 12) and MEDLINE (1946 to 22 January 2013). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators and experts in the field.
SELECTION CRITERIA
Randomised controlled trials in children or adults with partial onset seizures or generalised onset tonic-clonic seizures with a comparison of oxcarbazepine monotherapy with phenytoin monotherapy.
DATA COLLECTION AND ANALYSIS
This was an individual participant data review. Outcomes were time to (a) treatment withdrawal (b) 12-month remission (c) six-month remission and (d) first seizure post randomisation. We used Cox proportional hazards models to obtain study-specific estimates of hazard ratios (HR) with 95% confidence intervals (CI) with the generic inverse variance method used to obtain the overall pooled HR and 95% CI.
MAIN RESULTS
Individual participant data were available for 480 out of 517 participants (93%) from three included trials. For remission outcomes, a HR > 1 indicates an advantage to phenytoin and for first seizure and withdrawal outcomes a HR > 1 indicates an advantage to oxcarbazepine.The main overall results (pooled HR, 95% CI) were: (i) time to withdrawal of allocated treatment 1.65 (1.08 to 2.52), (ii) time to 12-month remission 0.92 (0.68 to 1.24), (iii) time to six-month remission 0.90 (0.70 to 1.15), (iv) time to first seizure 1.07 (0.83 to 1.39). Results indicate a statistically significant advantage for oxcarbazepine over phenytoin for time to treatment withdrawal, but insufficient evidence to suggest a difference between the drugs for other outcomes. By epilepsy type, there is no significant advantage for either drug for generalised epilepsy, however there is a significant advantage for partial epilepsy with oxcarbazepine for time to treatment withdrawal (HR 1.95; 95% CI 1.15 to 3.33).
AUTHORS' CONCLUSIONS
For participants with partial onset seizures oxcarbazepine is significantly less likely to be withdrawn, but current data do not allow a statement as to whether oxcarbazepine is equivalent, superior or inferior to phenytoin in terms of seizure control. However, the design of the studies may have biased seizure outcomes and misclassification of epilepsy type may have biased withdrawal rates.
Topics: Anticonvulsants; Carbamazepine; Epilepsies, Partial; Epilepsy; Humans; Induction Chemotherapy; Oxcarbazepine; Phenytoin; Randomized Controlled Trials as Topic
PubMed: 23728645
DOI: 10.1002/14651858.CD003615.pub3 -
CNS Drugs Dec 2020Recent studies have shown conflicting results regarding the effectiveness of levetiracetam for treating benzodiazepine-refractory status epilepticus (SE) compared with... (Comparative Study)
Comparative Study Meta-Analysis
Levetiracetam versus Phenytoin for the Pharmacotherapy of Benzodiazepine-Refractory Status Epilepticus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
Recent studies have shown conflicting results regarding the effectiveness of levetiracetam for treating benzodiazepine-refractory status epilepticus (SE) compared with phenytoin. Therefore, a meta-analysis was carried out to assess the value of levetiracetam versus phenytoin in the pharmacotherapy of benzodiazepine-refractory SE.
OBJECTIVE
The aim of this systematic review and meta-analysis was to compare the efficacy and safety of levetiracetam and phenytoin in the treatment of benzodiazepine-refractory SE.
METHODS
The MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) that had been conducted to evaluate levetiracetam versus phenytoin for benzodiazepine-refractory SE, to April 2020. The data were assessed using Review Manager 5.3 software. The risk ratio (RR) was analyzed using dichotomous outcomes, and calculated using a random-effect model.
RESULTS
We pooled 1850 patients from 12 RCTs. Patients in the levetiracetam group had a significantly higher rate of clinical seizure cessation than in the phenytoin group (75.2% vs. 67.8%; RR 1.14, 95% confidence interval [CI] 1.05-1.25, p = 0.003). Moreover, less adverse events were observed in the levetiracetam group than in the phenytoin group (17.8% vs. 21.4%; RR 0.82, 95% CI 0.70-0.97, p = 0.02). In subgroup analysis, clinical seizure cessation was achieved more frequently with a higher dose of levetiracetam (> 30 mg/kg) [RR 1.15, 95% CI 1.00-1.32, p = 0.05]. Furthermore, in the subgroup of children, levetiracetam showed a higher rate of clinical seizure cessation than phenytoin (RR 1.13, 95% CI 1.02-1.25, p = 0.02).
CONCLUSION
Pharmacotherapy for BZD-refractory SE by LEV is superior to PHT in efficacy and safety outcomes.
Topics: Anticonvulsants; Benzodiazepines; Child; Humans; Levetiracetam; Odds Ratio; Phenytoin; Randomized Controlled Trials as Topic; Status Epilepticus
PubMed: 33111213
DOI: 10.1007/s40263-020-00770-0 -
British Journal of Clinical Pharmacology Jul 2016The aim of this study was to perform an up-to-date systematic review and meta-analysis on the efficacy and safety of prophylactic administration of levetiracetam in... (Comparative Study)
Comparative Study Meta-Analysis Review
AIMS
The aim of this study was to perform an up-to-date systematic review and meta-analysis on the efficacy and safety of prophylactic administration of levetiracetam in brain tumour patients.
METHOD
A systematic review of studies published until April 2015 was conducted using Scopus/Elsevier, EMBASE and MEDLINE. The search was limited to articles reporting results from adult patients, suffering from brain tumour, undergoing supratentorial craniotomy for tumour resection or biopsy and administered levetiracetam in the perioperative period for seizure prophylaxis. Outcomes included the efficacy and safety of levetiracetam, as well as the tolerability of the specific regimen, defined by the discontinuation of the treatment due to side effects.
RESULTS
The systematic review included 1148 patients from 12 studies comparing levetiracetam with no treatment, phenytoin and valproate, while only 243 patients from three studies, comparing levetiracetam vs phenytoin efficacy and safety, were included in the meta-analysis. The combined results from the meta-analysis showed that levetiracetam administration was followed by significantly fewer seizures than treatment with phenytoin (OR = 0.12 [0.03-0.42]: χ(2) = 1.76: I(2) = 0%). Analysis also showed significantly fewer side effects in patients receiving levetiracetam, compared to other groups (P < 0.05). The combined results showed fewer side effects in the levetiracetam group compared to the phenytoin group (OR = 0.65 [0.14-2.99]: χ(2) = 8.79: I(2) = 77%).
CONCLUSIONS
The efficacy of prophylaxis with levetiracetam seems to be superior to that with phenytoin and valproate administration. Moreover, levetiracetam use demonstrates fewer side effects in brain tumour patients. Nevertheless, high risk of bias and moderate methodological quality must be taken into account when considering these results.
Topics: Anticonvulsants; Craniotomy; Humans; Levetiracetam; Perioperative Care; Phenytoin; Piracetam; Seizures; Supratentorial Neoplasms; Valproic Acid
PubMed: 26945547
DOI: 10.1111/bcp.12926