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Journal of Clinical Neuroscience :... Jul 2021Status epilepticus (SE) is the second most critical neurological illness after cerebrovascular disease. Phenytoin has traditionally been considered the second-line drug... (Comparative Study)
Comparative Study Meta-Analysis
Status epilepticus (SE) is the second most critical neurological illness after cerebrovascular disease. Phenytoin has traditionally been considered the second-line drug of first choice after failure of first-line treatment using benzodiazepines. In recent years, levetiracetam has been proposed as a potential substitute for phenytoin. To comprehensively evaluate the efficacy and safety of levetiracetam and phenytoin in the treatment of patients with established SE, we integrated the data from 11 eligible studies and conducted a systematic review and meta-analysis. The PubMed, Web of Science, Cochrane Library, and Embase databases were searched to identify eligible articles reporting outcomes including clinical seizure cessation within 60 min, clinical recurrence rate within 24 h, good final outcome at discharge, and adverse events (AEs) of treatment with levetiracetam and phenytoin. Our study included a total of 11 trials including a total of 1933 patients. The outcomes showed that the pooled Risk Raito (RR) of clinical seizure cessation within 60 min was 1.08 (95% CI = 1.02-1.14, P = 0.01). The pooled RR of clinical recurrence rate within 24 h was 1.03 (95% CI = 0.66-1.59, P = 0.91). The pooled RR of AEs was 0.83 (95% CI = 0.57-1.21, P = 0.34). The pooled RRs of life-threatening hypotension and acute respiratory depression were 0.29 (95% CI = 0.10-0.81, P = 0.02) and 0.63 (95% CI = 0.40-0.98, P = 0.04), respectively. Levetiracetam might be more effective than phenytoin for the treatment of established SE and is associated with a lower incidence of more serious AEs. Levetiracetam can be used as an alternative to phenytoin for the treatment of benzodiazepine-refractory SE.
Topics: Anticonvulsants; Humans; Levetiracetam; Phenytoin; Status Epilepticus
PubMed: 34053822
DOI: 10.1016/j.jocn.2021.05.004 -
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 -
Acta Neurologica Scandinavica Oct 2021To compare the evidence on efficacy, safety, tolerability, and impact on short term/long functional outcome of lacosamide (LCM) and phenytoin (PHT) in patients with...
OBJECTIVES
To compare the evidence on efficacy, safety, tolerability, and impact on short term/long functional outcome of lacosamide (LCM) and phenytoin (PHT) in patients with status epilepticus.
MATERIALS & METHODS
We conducted a systematic literature search of relevant electronic databases using a suitable search strategy to identify studies directly comparing PHT and LCM, irrespective of dose and duration in patients with convulsive and/or nonconvulsive status epilepticus (SE). We used a standardized assessment form to extract information on the study design, data sources, methodologic framework, efficacy, and adverse events attributed to PHT and LCM from included studies and compared the efficacy and safety outcomes, using a fixed/random effect model.
RESULTS
Five studies were found to be eligible for inclusion out of 192 search items, enrolling a total of 115 and 166 participants (predominantly with SE) in LCM and PHT arm, respectively. Baseline characteristics were comparable between both arms. The proportion with seizure control was comparable between both arms (57.3% in LCM vs. 45.7% in PHT arm, p = 0.28) and even in the subgroup analysis separately for convulsive and non-convulsive SE. Proportion with treatment-emergent adverse events (TEAE) were comparable in both (17.6% vs. 12.2%, p = 0.20), but serious adverse events (SAE) were higher in PHT arm (5.1% vs. 0.8%, p = 0.049). The proportion with all-cause mortality and survival with moderate-severe disability were comparable between both arms (p = 0.23 and 0.37, respectively).
CONCLUSION
LCM has comparable efficacy with fewer SAEs as compared to PHT for achieving seizure control in patients with SE.
Topics: Anticonvulsants; Humans; Lacosamide; Phenytoin; Seizures; Status Epilepticus; Treatment Outcome
PubMed: 33999428
DOI: 10.1111/ane.13469 -
The International Journal of Lower... Jun 2023There are a variety of dressings for wound healing. For this reason, research can assist in the choice and proper use of the intervention. This current view of the... (Review)
Review
There are a variety of dressings for wound healing. For this reason, research can assist in the choice and proper use of the intervention. This current view of the effectiveness of dressing on diabetic foot ulcers (DFUs) in patients with type 2 diabetes mellitus. This study is a systematic review of clinical trials selected in 4 databases: PubMed, Scopus, Web of Science, and Cochrane. Studies without language restriction, published between 2009 and 2020, were included. The search resulted in the identification of 5651 articles, of which 58 met all inclusion criteria. Among these, 2 biomaterials (D-acellular dermal matrix and keratinocyte) and phenytoin were highlighted for achieving healing rates of 100% and 95.82% ± 2.22%, respectively. The literature presents several alternatives with different actions, cure rates, reduction rates, and varied cost benefits. The growth in the use of biomaterials for the treatment of DFU can be seen in this study.
Topics: Humans; Bandages, Hydrocolloid; Diabetes Mellitus, Type 2; Diabetic Foot; Wound Healing
PubMed: 33949242
DOI: 10.1177/15347346211013189 -
World Neurosurgery Jul 2021Frequency of clinical seizures may be as high as 16% in patients with spontaneous intracerebral hemorrhage (ICH). Current guidelines recommend against antiepileptic drug... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Frequency of clinical seizures may be as high as 16% in patients with spontaneous intracerebral hemorrhage (ICH). Current guidelines recommend against antiepileptic drug (AED) prophylaxis, but this recommendation is based on older trials, and the effect of newer AEDs is uncertain. The aim of this review was to study effects of AEDs on seizure occurrence and outcome in patients with spontaneous ICH.
METHODS
We searched key databases using combinations of the following terms: "levetiracetam," "prophylaxis," "ICH," "intracerebral hemorrhage," "intraparenchymal hemorrhage." Selected studies were reviewed for level of evidence and overall quality of data using Grading of Recommendations, Assessment, Development and Evaluations criteria. A meta-analysis was performed to evaluate seizure prevention, functional outcome, and mortality in patients with seizure prophylaxis compared with no prophylaxis following spontaneous ICH.
RESULTS
Seven articles met inclusion criteria and were graded level III studies. Administration of AEDs was not associated with reduced seizure risk (odds ratio 1.14, 95% confidence interval 0.47-2.77, P = 0.77). There was an association between AED prophylaxis and poor functional outcome (odds ratio 1.65, 95% confidence interval 1.17-2.31, P = 0.004) but not mortality (odds ratio 1.04, 95% confidence interval 0.62-1.72, P = 0.89). The overall quality of evidence using Grading of Recommendations, Assessment, Development and Evaluations criteria was low.
CONCLUSIONS
This systematic review and meta-analysis including recent studies focusing on newer AEDs supports the 2015 guidelines regarding AED use in spontaneous ICH. There are some important caveats, including a possible confounding association between AED use and higher ICH score and the overall poor quality of the available data. A randomized clinical trial may be helpful.
Topics: Anticonvulsants; Cerebral Hemorrhage; Humans; Levetiracetam; Phenytoin; Piracetam; Seizures
PubMed: 33940261
DOI: 10.1016/j.wneu.2021.04.083 -
Clinical Toxicology (Philadelphia, Pa.) Jun 2021Seizures are a common manifestation of toxic exposures requiring immediate and possibly ongoing management. Guidelines recommend benzodiazepines as first-line therapy...
BACKGROUND
Seizures are a common manifestation of toxic exposures requiring immediate and possibly ongoing management. Guidelines recommend benzodiazepines as first-line therapy for toxic seizures; however, there is a paucity of literature regarding optimal secondary treatment. We systematically evaluated the available literature for second-line treatment of toxic seizures.
METHODS
We searched PubMed, Embase, PsychINFO, Cochrane Library, Web of Science, Google Scholar, and International Pharmaceutical Abstracts from inception through August of 2018, following PRISMA Guideline. The MESH terms focused on identifying treatments for seizures induced by drugs or other potentially toxic substances. We excluded the articles if they involved animals, had seizures resulting from alcohol withdrawal, were case reports, or not peer-reviewed. Our primary outcome was seizure termination and/or suppression by the second-line agent as agreed upon by two authors. We used descriptive statistics for analysis.
RESULTS
We identified six case series that met inclusion and exclusion criteria. Included case series contained nine to 235 patient cases each. The most common xenobiotic exposures were bupropion, isoniazid, and anti-psychotics. The description of seizure type and duration was diverse. First-line treatments were primarily benzodiazepines. Secondary treatments included propofol, barbiturates, phenytoin, valproic acid, and levetiracetam. Patient outcomes differed, attributable to any of the following: mixed toxic substances, drug-drug interactions, inability to control seizures, or toxicity of the anti-epileptic drugs (AED) themselves. Few cases specifically discussed the success of secondary treatment administration to suppress or terminate seizures.
CONCLUSIONS
Available literature discussing second-line treatment for toxic seizures is of poor quality with high heterogeneity. Although the majority of articles used similar second-line agents, it is difficult to compare the efficacy of the regimens. Additional studies are necessary to identify the most efficacious second-line therapies in toxic seizures.
Topics: Anticonvulsants; Female; Humans; Male; Phenytoin; Seizures; Valproic Acid
PubMed: 33755521
DOI: 10.1080/15563650.2021.1894332 -
Seizure Apr 2021Spontaneous intracerebral haemorrhage (ICH) is associated with high mortality and high morbidity, including seizures. Seizure prophylaxis is "not recommended" by the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Spontaneous intracerebral haemorrhage (ICH) is associated with high mortality and high morbidity, including seizures. Seizure prophylaxis is "not recommended" by the American Stroke Association, but practice variation still exists due to inconclusive data. We performed a meta-analysis to assess the current relevant literature to determine the efficacy of seizure prophylaxis following ICH.
METHODS
We performed searches of PubMed, Scopus, and Embase up to September 15, 2020. We included observational and randomized controlled studies reporting seizure prophylaxis and occurrence in adults with ICH. Outcomes were seizures, as defined by the authors, within 14 days of ICH and at the longest point of follow-up. We used random-effects models to estimate the odds ratios (ORs) for seizure prophylaxis and outcomes. The PROSPERO registration was CRD42019140493.
RESULTS
We included 8 studies (2852 patients) in our analysis. The mean (± standard deviation) age of the pooled patients was 65 (±4) years; 39 % (± 5%) were female. Seizure prophylaxis did not prevent seizures at the longest follow-up time (OR 0.708, 95 % CI 0.438-1.143, p = 0.158, I2 = 34 %). This result was confirmed in subgroup analyses using categorical variables and in meta-regressions using continuous variables. Additionally, seizure prophylaxis was not associated with preventing early seizures, defined as < 14 days of ICH (OR 0.66, 95 % CI 0.21-2.08, p = 0.48, I2 = 35 %).
CONCLUSION
Seizure prophylaxis following ICH was not associated with seizure prevention in adults. Most included studies were observational. Further randomized controlled trials examining the efficacy of seizure prophylaxis in high-risk patients and different types of antiepileptic drugs are needed.
Topics: Aged; Anticonvulsants; Cerebral Hemorrhage; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Seizures
PubMed: 33713891
DOI: 10.1016/j.seizure.2021.02.029 -
Journal of Tropical Pediatrics Jan 2021Phenobarbitone is used as a first-line drug for neonatal seizures. However, its poor short- and long-term safety profile is concerning. We aim to systematically... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Phenobarbitone is used as a first-line drug for neonatal seizures. However, its poor short- and long-term safety profile is concerning. We aim to systematically synthesize the data on the efficacy and safety of phenobarbitone as a first-line agent and compare it against other anti-epileptic drugs (AEDs) in neonates.
METHODS
Using keywords related to the study population (neonatal seizure) and intervention (phenobarbitone), we searched CENTRAL, Embase, PubMed and Web of Science until 15 December 2020. Randomized controlled trials (RCTs) comparing phenobarbitone with any other AED as first-line therapy for seizure control in the neonates were considered eligible. The random-effect meta-analysis was done using RevMan 5.3 software.
RESULTS
We screened through 443 records and identified nine eligible studies (719 participants). Five RCTs comparing phenobarbitone with levetiracetam did not find any difference in seizure control with the first dose [risk ratio (RR) 1.43, 95% CI 0.79-2.57] or adverse effects (RR 4.66; 95% CI 0.33-65.83). Two trials comparing phenobarbitone and phenytoin also did not find any difference in seizure control with the first dose (RR 2.09; 95% CI 0.31-14.03) and other outcomes. Only one RCT compared phenobarbitone and lorazepam and found lorazepam to be more efficacious in seizure control with the first dose (RR 0.71; 95% CI 0.53-0.94). Three trials compared neurodevelopmental outcomes, in which levetiracetam was better in two, whereas one did not find any difference.
CONCLUSION
Phenobarbitone is at least as efficacious and safe as other drugs like phenytoin and levetiracetam. The data over the long-term neurodevelopmental outcome are lacking. The existing evidence is insufficient to recommend other drugs over phenobarbitone.
Topics: Anticonvulsants; Carbamazepine; Humans; Infant, Newborn; Phenobarbital; Phenytoin; Seizures
PubMed: 33598701
DOI: 10.1093/tropej/fmab008 -
CNS Drugs Feb 2021Cutaneous adverse drug reactions (cADRs) are one of the most common, severe, and life-threatening types of adverse reactions following treatment with antiseizure... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Cutaneous adverse drug reactions (cADRs) are one of the most common, severe, and life-threatening types of adverse reactions following treatment with antiseizure medications (ASMs). Some studies have reported a higher incidence of ASM-induced cADRs in females than in males.
OBJECTIVE
This study sought to perform a systematic review, meta-analysis, and meta-regression to compare the ASM cADR risks between females and males.
METHODS
We searched the literature using three databases (EMBASE, PubMed, and Web of Science) between October 1998 and November 2018, later updated to October 2019. Studies were included in the meta-analysis if they met the following criteria: (1) observational studies that estimated the incidence of cADRs related to ASMs; (2) provided the risk or odds ratio (OR) for cADRs among female and male patients exposed to ASMs; and (3) provided information on patients' characteristics. We assessed the impact of study characteristics, publication bias, and measures to reduce bias, and performed a DerSimonian and Laird random effects meta-analysis.
RESULTS
We included 28 studies in this review. Of these, seven studies were eligible for inclusion in the meta-analysis, involving a total of 223,209 patients. Overall, females were more likely to develop cADRs to ASMs than males (OR 1.76, 95% confidence interval [CI] 1.55-1.99). The largest differences were observed in patients prescribed lamotrigine (OR 2.17, 95% CI 1.53-3.08, p < 0.001) and carbamazepine (OR 1.63, 95% CI 1.02-2.60, p = 0.042). Also, the OR trended higher for phenytoin (OR 2.46, 95% CI 0.79-7.65, p = 0.12), followed by oxcarbazepine (OR 1.91, 95% CI 0.75-4.85, p = 0.18) and sodium valproate (OR 0.60, 95% CI 0.12-2.99, p = 0.53), but the difference did not reach statistical significance. In the remaining 21 studies, 13 reported numerically higher risk of cADRs among females compared to male patients, and in five of these, the difference was statistically significant.
CONCLUSION
Our findings confirmed that females are more susceptible to cADRs induced by ASMs than males. More research is needed to understand the pathophysiological mechanisms for this difference.
PROTOCOL REGISTRATION
PROSPERO (CRD42018111943).
Topics: Anticonvulsants; Drug Eruptions; Female; Humans; Incidence; Male; Sex Factors
PubMed: 33580477
DOI: 10.1007/s40263-021-00794-0 -
Clinical Pharmacokinetics Mar 2021Levetiracetam has been widely used as a treatment option for different types of epilepsy in both adults and children. Because of its large between-subject variability,...
BACKGROUND
Levetiracetam has been widely used as a treatment option for different types of epilepsy in both adults and children. Because of its large between-subject variability, several population pharmacokinetic studies have been performed to identify its pharmacokinetic covariates, and thus facilitate individualised therapy.
OBJECTIVE
The aim of this review was to provide a synopsis for population pharmacokinetic studies of levetiracetam and explore the identified influencing covariates.
METHODS
We systematically searched the PubMed and Embase databases from inception to 30 June 2020. The information on study designs, target population, model characteristics, and identified covariates was summarised. Moreover, the pharmacokinetic profiles were compared among neonates, children, and adults.
RESULTS
Fourteen studies were included, among which two involved neonates, four involved children, two involved both children and adults, and six involved adults only. The median value of apparent clearance for children (0.074 L/h/kg [range 0.038-0.079]) was higher than that for adults (0.054 L/h/kg [range 0.039-0.061]). Body weight was found to significantly influence the apparent clearance and volume of distribution, whereas renal function influenced the clearance. Likewise, coadministration with enzyme-inducing antiepileptic drugs (such as carbamazepine and phenytoin) increased the drug clearance by 9-22%, whereas coadministration with valproate acid decreased it by 18.8%.
CONCLUSION
Levetiracetam dose regimen is dependent on the body size and renal function of patients. Further studies are needed to evaluate levetiracetam pharmacokinetics in neonates and pregnant women.
Topics: Adult; Anticonvulsants; Carbamazepine; Child; Female; Humans; Infant, Newborn; Levetiracetam; Phenytoin; Piracetam; Pregnancy
PubMed: 33447943
DOI: 10.1007/s40262-020-00963-2