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Acta Clinica Belgica Feb 2022: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an adverse and severe skin reaction due to patients' susceptibility to medications, including...
: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an adverse and severe skin reaction due to patients' susceptibility to medications, including phenytoin. The objective was to explore the characteristics of patients with DRESS secondary to phenytoin through a systematic review.: We describe a case of DRESS syndrome secondary to phenytoin in a patient with previous exposure to this drug. A systematic literature review of cases of phenytoin-induced DRESS syndrome was conducted in PubMed/Medline, Scopus and Web of Science until May 2019.: 37 articles describing 40 cases of DRESS syndrome were selected. Mean age of onset was 33 years, without gender difference. Symptoms started between two and 90 days (mean ± 23 days). Liver and respiratory tract were most frequently involved, and eosinophilia was a common feature, it was presented with an average value of 9.7%. A discussion of the case and qualitative synthesis of the evidence reported in the literature were made.: Patients and presentation characteristics will mostly be presented according to the criteria used by RegiSCAR. It is recommended to consider adequate monitoring of adverse reactions to antiepileptic drugs such as DRESS syndrome, given its severity and high lethality.
Topics: Adult; Anticonvulsants; Drug Hypersensitivity Syndrome; Eosinophilia; Humans; Phenytoin; Skin
PubMed: 32469684
DOI: 10.1080/17843286.2020.1767459 -
Neurology Apr 2024To undertake a systematic review of the available literature to examine the relationship between prenatal antiseizure medication (ASM) exposure and adverse postnatal...
BACKGROUND AND OBJECTIVES
To undertake a systematic review of the available literature to examine the relationship between prenatal antiseizure medication (ASM) exposure and adverse postnatal neurodevelopmental outcomes, focusing on social, emotional, behavioral, and adaptive domains of human function, and the frequency of neurodevelopmental and psychiatric disorders in ASM-exposed offspring.
METHODS
Electronic searches of MEDLINE, PsychINFO, and EMBASE were conducted and limited to studies published between 1990 and 2023 in English. Studies were eligible if they prospectively or retrospectively reported neurodevelopmental outcomes of ASM-exposed offspring. The Newcastle-Ottawa scale was used to conduct methodologic quality assessments of included studies, and a narrative synthesis integrated the review findings.
RESULTS
Forty-three studies were included. Valproate has been consistently associated with a 2- to 4-fold increased risk of autism spectrum disorder (ASD), 2- to 5-fold increased risk of intellectual disability (ID), and poor adaptive functioning. Growing evidence indicates that topiramate is associated with a 2-fold increased risk of ASD and 3- to 4-fold increased risk of ID. The risks of adverse neurodevelopmental outcomes for valproate and topiramate seem to be dose dependent. Phenobarbital has been suggested to be associated with deleterious neurodevelopmental effects, but data are limited. Levetiracetam has recently been linked with an increased risk of attention deficit hyperactivity disorder and anxiety disorders in a single study. Carbamazepine has been associated with variable neurodevelopmental outcomes. Lamotrigine seems to be "safe" in terms of postnatal neurodevelopment. Data for oxcarbazepine, phenytoin, and clonazepam are limited but seem to have little-to-no risk of adverse outcomes. Evidence for the remaining ASMs, including gabapentin, pregabalin, lacosamide, zonisamide, clobazam, perampanel, ethosuximide, or brivaracetam, is lacking. Several methodologic limitations impeded data synthesis, including heterogeneity in outcome measures and small samples of monotherapy exposures.
DISCUSSION
The findings of this review support the conclusion that valproate and topiramate use during pregnancy is associated with a significantly increased risk of neurodevelopmental effects on the fetus. Apart from lamotrigine, which seems to be free of adverse neurodevelopmental effects, data for the other ASMs are mixed or inadequate to draw definite conclusions. Further research into the neurodevelopmental effects of prenatal exposure to ASMs, including most newer agents, is much needed.
Topics: Pregnancy; Female; Humans; Valproic Acid; Lamotrigine; Topiramate; Autism Spectrum Disorder; Retrospective Studies; Anticonvulsants
PubMed: 38531021
DOI: 10.1212/WNL.0000000000209175 -
The Cochrane Database of Systematic... Aug 2013This is an updated version of the previously published Cochrane review (Issue 4, 2009)Worldwide, phenytoin and valproate are commonly used antiepileptic drugs. It is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the previously published Cochrane review (Issue 4, 2009)Worldwide, phenytoin and valproate are commonly used antiepileptic drugs. It is generally believed that phenytoin is more effective for partial onset seizures, and that valproate is more effective for generalised onset tonic-clonic seizures with or without other generalised seizure types.
OBJECTIVES
To review the best evidence comparing phenytoin and valproate when used as monotherapy in individuals with partial onset seizures or generalised onset tonic-clonic seizures with or without other generalised seizure types.
SEARCH METHODS
We searched the Cochrane Epilepsy Group's Specialised Register (19 February 2013), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, The Cochrane Library, January 2013), MEDLINE (1946 to 18 February 2013), SCOPUS (19 February 2013), ClinicalTrials.gov (19 February 2013), and WHO International Clinical Trials Registry Platform ICTRP (19 February 2013). We handsearched relevant journals, 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 valproate monotherapy versus phenytoin monotherapy.
DATA COLLECTION AND ANALYSIS
This was an individual patient data review. Outcomes were time to (a) treatment withdrawal (b) 12-month remission (c) six-month remission and (d) first seizure post randomisation. Cox proportional hazards regression models were used to obtain study-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs) with the generic inverse variance method used to obtain the overall pooled HR and 95% CI.
MAIN RESULTS
Individual patient data were available for 669 individuals out of 1119 eligible individuals from five out of 11 trials, 60% of the potential data. Results apply to generalised tonic-clonic seizures, but not absence or myoclonus seizure types. For remission outcomes, HR > 1 indicates an advantage for phenytoin and for first seizure and withdrawal outcomes HR > 1 indicates an advantage for valproateThe main overall results (pooled HR adjusted for seizure type, 95% CI) were time to (a) withdrawal of allocated treatment 1.09 (0.76 to 1.55); (b) 12-month remission 0.98 (0.78 to 1.23); (c) six-month remission 0.95 (0.78 to 1.15) and (d) first seizure 0.93 (0.75 to 1.14). The results suggest no overall difference between the drugs for these outcomes. No statistical interaction between treatment and seizure type (partial versus generalised) was found, but misclassification of seizure type may have confounded the results of this review.
AUTHORS' CONCLUSIONS
We have not found evidence that a significant difference exists between phenytoin and valproate for the outcomes examined in this review. However misclassification of seizure type may have confounded the results of this review. Results do not apply to absence or myoclonus seizure types. No outright evidence was found to support or refute current treatment policies.
Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Humans; Phenytoin; Randomized Controlled Trials as Topic; Seizures; Valproic Acid
PubMed: 23970302
DOI: 10.1002/14651858.CD001769.pub2 -
The Cochrane Database of Systematic... Feb 2010Aggression is a major public health issue and is integral to several mental health disorders. Antiepileptic drugs may reduce aggression by acting on the central nervous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Aggression is a major public health issue and is integral to several mental health disorders. Antiepileptic drugs may reduce aggression by acting on the central nervous system to reduce neuronal hyper-excitability associated with aggression.
OBJECTIVES
To evaluate the efficacy of antiepileptic drugs in reducing aggression and associated impulsivity.
SEARCH STRATEGY
We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, metaRegister of Controlled Trials (mRCT) and ClinicalTrials.gov to April 2009. We also searched Cochrane Schizophrenia Group's register of trials on aggression, National Research Record and handsearched for studies.
SELECTION CRITERIA
Prospective, placebo-controlled trials of antiepileptic drugs taken regularly by individuals with recurrent aggression to reduce the frequency or intensity of aggressive outbursts.
DATA COLLECTION AND ANALYSIS
Three authors independently selected studies and two authors independently extracted data. We calculated standardised mean differences (SMDs), with odds ratios (ORs) for dichotomous data.
MAIN RESULTS
Fourteen studies with data from 672 participants met the inclusion criteria. Five different antiepileptic drugs were examined. Sodium valproate/divalproex was superior to placebo for outpatient men with recurrent impulsive aggression, for impulsively aggressive adults with cluster B personality disorders, and for youths with conduct disorder, but not for children and adolescents with pervasive developmental disorder. Carbamazepine was superior to placebo in reducing acts of self-directed aggression in women with borderline personality disorder, but not in children with conduct disorder. Oxcarbazepine was superior to placebo for verbal aggression and aggression against objects in adult outpatients. Phenytoin was superior to placebo on the frequency of aggressive acts in male prisoners and in outpatient men including those with personality disorder, but not on the frequency of 'behavioral incidents' in delinquent boys.
AUTHORS' CONCLUSIONS
The authors consider that the body of evidence summarised in this review is insufficient to allow any firm conclusion to be drawn about the use of antiepileptic medication in the treatment of aggression and associated impulsivity. Four antiepileptics (valproate/divalproex, carbamazepine, oxcarbazepine and phenytoin) were effective, compared to placebo, in reducing aggression in at least one study, although for three drugs (valproate, carbamazepine and phenytoin) at least one other study showed no statistically significant difference between treatment and control conditions. Side effects were more commonly noted for the intervention group although adverse effects were not well reported. Absence of information does not necessarily mean that the treatment is safe, nor that the potential gains from the medication necessarily balance the risk of an adverse event occurring. Further research is needed.
Topics: Adolescent; Adult; Aggression; Anger; Anticonvulsants; Antisocial Personality Disorder; Child; Disruptive, Impulse Control, and Conduct Disorders; Female; Hostility; Humans; Male; Medication Adherence; Randomized Controlled Trials as Topic
PubMed: 20166067
DOI: 10.1002/14651858.CD003499.pub3 -
Drugs in R&D Sep 2017Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood. (Review)
Review
BACKGROUND
Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood.
OBJECTIVES
The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed.
METHODS
MEDLINE (1946-3 May, 2017), EMBASE (1974-3 May, 2017), Pharmacogenomics Knowledge Base, and Public Health Genomics Knowledge Base online databases were searched. Studies were included if genotyping and analyses of phenytoin pharmacokinetics were performed in patients of the Middle East and North Africa region. Study quality was assessed using a National Institutes of Health assessment tool. A secondary search identified studies reporting genotypic and allelic frequencies of assessed genetic polymorphisms within the Middle East and North Africa region.
RESULTS
Five studies met the inclusion criteria. CYP2C9, CYP2C19, and multidrug resistance protein 1 C3435T variants were evaluated. While CYP2C9*2 and *3 variants significantly reduced phenytoin metabolism, the impacts of CYP2C19*2 and *3 variants were unclear. The multidrug resistance protein 1 CC genotype was associated with drug-resistant epilepsy, but reported impacts on phenytoin pharmacokinetics were conflicting. Appreciable variability in minor allele frequencies existed both between and within countries of the Middle East and North Africa region.
CONCLUSIONS
CYP2C9 decrease-of-function alleles altered phenytoin pharmacokinetics in patients originating from the Middle East and North Africa region. The impacts of CYP2C19 and multidrug resistance protein 1 C3435T variants on phenytoin pharmacokinetic and clinical outcomes are unclear and require further investigation. Future research should focus on the clinical outcomes associated with phenytoin therapy. PROSPERO 2017: CRD42017057850.
Topics: Africa, Northern; Anticonvulsants; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Epilepsy; Genotype; Humans; Middle East; Phenytoin; Polymorphism, Genetic
PubMed: 28748348
DOI: 10.1007/s40268-017-0195-7 -
The Cochrane Database of Systematic... May 2012Antiepileptic drugs have been used in pain management since the 1960s; some have shown efficacy in treating different neuropathic pain conditions. Phenytoin is an... (Review)
Review
BACKGROUND
Antiepileptic drugs have been used in pain management since the 1960s; some have shown efficacy in treating different neuropathic pain conditions. Phenytoin is an established antiepileptic drug that has been used occasionally to treat intractable trigeminal neuralgia.
OBJECTIVES
To assess the analgesic efficacy and adverse effects of the antiepileptic drug phenytoin in neuropathic pain and fibromyalgia.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2), MEDLINE, and EMBASE to 28 February 2012, together with reference lists of retrieved papers and reviews, and ClinicalTrials.gov.
SELECTION CRITERIA
We planned to include randomised, double-blind studies of eight weeks duration or longer, comparing phenytoin with placebo or another active treatment in chronic neuropathic pain or fibromyalgia.
DATA COLLECTION AND ANALYSIS
Two review authors would independently extract data for efficacy and adverse events, and examine issues of study quality.
MAIN RESULTS
We did not identify any studies that satisfied the inclusion criteria.
AUTHORS' CONCLUSIONS
This review uncovered no evidence of sufficient quality to support the use of phenytoin in chronic neuropathic pain or fibromyalgia.
Topics: Adult; Analgesics; Anticonvulsants; Fibromyalgia; Humans; Neuralgia; Pain Management; Phenytoin
PubMed: 22592741
DOI: 10.1002/14651858.CD009485.pub2 -
Epilepsy Research Jul 2015To characterize the association between commonly used anti-epileptic drugs (AEDs) and plasma lipid levels in patients with epilepsy. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To characterize the association between commonly used anti-epileptic drugs (AEDs) and plasma lipid levels in patients with epilepsy.
METHODS
We sought observational studies that reported association between commonly used AEDs and plasma lipid levels in patients. The primary outcome was low-density lipoprotein (LDL) cholesterol. High-density lipoprotein (HDL), total cholesterol and triglyceride were secondary outcomes. The control group included healthy controls, pre-treatment patients or patients treated with other AEDs. We conducted a systematic search of major bibliographic databases and review of reference lists of primary articles and reviews. Primary comparisons of interest were: AED monotherapy vs. no AED use, monotherapy with one AED vs. other AED, and AED polytherapy vs. no AED use.
RESULTS
31 studies in 4126 people were identified. Carbamazepine, phenytoin and valproic acid were the most commonly studied drugs and were also implicated in causing considerable changes in plasma lipid levels in treated patients. There was an increase in LDL and total cholesterol levels with use of these three drugs; however, carbamazepine and phenytoin were also associated with higher levels of HDL. We could not identify one particular AED which was worse than the other in head-to-head comparison. We were unable to identify a particular polytherapy regimen that was worse than others.
CONCLUSION
We found evidence to suggest that some AEDs may negatively alter lipids levels in patients with epilepsy. Both treating physicians and people with epilepsy need to be vigilant in managing their vascular risk factors to avoid vascular disease.
Topics: Animals; Anticonvulsants; Databases, Bibliographic; Dyslipidemias; Epilepsy; Humans; Lipids
PubMed: 25986191
DOI: 10.1016/j.eplepsyres.2015.03.002 -
The International Journal of... Jan 2021Status epilepticus (SE) is a common neurologic emergency. The present study constitutes a meta-analysis of published randomized control trials (RCTs) evaluating the use... (Meta-Analysis)
Meta-Analysis
Status epilepticus (SE) is a common neurologic emergency. The present study constitutes a meta-analysis of published randomized control trials (RCTs) evaluating the use of intravenous sodium valproate (VPA) in SE. MEDLINE and Cochrane databases were comprehensively searched, while retrieved RCTs and meta-analyses were manually screened. Prespecified outcome measures included seizure-cessation, 24 h-efficacy, constitute (liver enzyme increase, arrhythmias, bone-marrow suppression, hypotension and respiratory depression) and severe (life-threatening) adverse events (AEs). Evidence synthesis was performed when appropriate, using Random-Effects (RE) or Fixed-Effects (FE) model based on heterogeneity between trials (homogeneity assumed when PQ > 0.1 and I < 50%). Outcomes were assessed using Odds-Ratios (ORs) and 95%Confidence-Intervals (95% CIs). Every available comparison was investigated in terms of efficacy and tolerability.Thirteen studies were retrieved and five comparisons were available, four of which involved two or more studies. Results were compatible with no significant difference between VPA and Phenytoin both in terms of efficacy and tolerability [seizure-cessation: FE-OR = 1.99, 95% CI = (0.83-4.75), 24 h-efficacy: FE-OR = 1.32, 95% CI = (0.60-2.89), composite AEs: FE-OR = 0.45, 95% CI = (0.17-1.21)]. Phenobarbital proved more commonly associated with composite AEs than VPA [seizure-cessation: RE-OR = 0.68, 95% CI = (0.05-9.44), 24 h-efficacy: RE-OR = 0.88, 95% CI = (0.02-33.9), composite AEs: FE-OR = 0.26, 95% CI = (0.09-0.82), severe AEs: FE-OR = 0.30, 95% CI = (0.04-2.28)]. Diazepam was determined inferior to VPA concerning safety issues [seizure-termination: FE-OR = 0.77, 95% CI = (0.34-1.79), severe respiratory depression: FE-OR = 0.06, 95% CI = (0.01-0.48), severe hypotension: FE-OR = 0.09, 95% CI = (0.01-0.72)]. The combination of Lorazepam (LZP) with VPA and the combination of LZP with Levetiracetam presented no difference in efficacy [24h-efficacy: FE-OR = 0.68, 95% CI = (0.37-1.24)]. Although, additional high-quality RCTs are warranted, according to our results, VPA can be considered a safe and effective option in the management of SE.
Topics: Administration, Intravenous; Anticonvulsants; Humans; Randomized Controlled Trials as Topic; Status Epilepticus; Valproic Acid
PubMed: 32075481
DOI: 10.1080/00207454.2020.1732967 -
BMJ Clinical Evidence Jun 2010Head injury in young adults is often associated with motor vehicle accidents, violence, and sports injuries. In older adults it is often associated with falls. Severe... (Review)
Review
INTRODUCTION
Head injury in young adults is often associated with motor vehicle accidents, violence, and sports injuries. In older adults it is often associated with falls. Severe head injury can lead to secondary brain damage from cerebral ischaemia resulting from hypotension, hypercapnia, and raised intracranial pressure. Severity of brain injury is assessed using the Glasgow Coma Scale (GCS). While about one quarter of people with severe brain injury (GCS score less than 8) will make a good recovery, about one third will die, and one fifth will have severe disability or be in a vegetative state.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to reduce complications of moderate to severe head injury as defined by Glasgow Coma Scale? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 17 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, anticonvulsants, corticosteroids, hyperventilation, hypothermia, and mannitol.
Topics: Acute Disease; Anticonvulsants; Brain Injuries; Brain Ischemia; Coma; Craniocerebral Trauma; Glasgow Coma Scale; Humans; Injury Severity Score; Intracranial Hypertension; Phenytoin
PubMed: 21418686
DOI: No ID Found -
Seizure May 2020To compare the efficacy and safety of levetiracetam and phenytoin for the treatment of established status epilepticus. (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVES
To compare the efficacy and safety of levetiracetam and phenytoin for the treatment of established status epilepticus.
METHODS
In this systematic review, we searched Medline, Embase, and Cochrane databases from their inception with no language restrictions until May 8, 2019 and updated on February 5, 2020, for randomized controlled trials comparing the efficacy and safety of levetiracetam and phenytoin for the treatment of established status epilepticus. A Meta-analysis was conducted to calculate the risk ratio (RR) using random-effects models.
RESULTS
We identified 7 trials with a total of 1028 participants. Levetiracetam was not associated with an increased rate of clinical seizure cessation within 60 min compared with phenytoin (RR, 1.02; 95 %CI, 0.92-1.13; I = 3%; 60.0 % [309/515] vs 59.3 % [275/463];12 more events [95 % CI, -48 to 77] per 1000 participants; moderate-quality evidence). Results were similar in the subgroup analysis of adults and children. The sample size met the optimum size in trial sequential analysis. There were also no statistically significant effects on good functional outcome (RR, 1.05; 95 % CI, 0.90-1.23), admission to critical care (RR, 1.09; 95 % CI, 0.95-1.24), or all-cause mortality (RR, 1.09; 95 % CI, 0.55-2.16).
CONCLUSIONS
Moderate-quality evidence suggested that levetiracetam was not significantly superior to phenytoin in seizure cessation in patients with established status epilepticus.
Topics: Anticonvulsants; Humans; Levetiracetam; Phenytoin; Randomized Controlled Trials as Topic; Status Epilepticus
PubMed: 32182544
DOI: 10.1016/j.seizure.2020.03.002