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Epileptic Disorders : International... Dec 2011In recent years, phenobarbital, as an antiepileptic drug, has become less popular based on adverse events, especially cognitive and behavioural side effects. Despite the... (Meta-Analysis)
Meta-Analysis Review
AIM
In recent years, phenobarbital, as an antiepileptic drug, has become less popular based on adverse events, especially cognitive and behavioural side effects. Despite the development of better tolerated new generation AEDs, phenobarbital is still widely used particularly in developing countries because of its low cost. The purpose of this review was to: (i) investigate whether phenobarbital can be safely used as an antiepileptic drug and (ii) determine the questions which need to be addressed in order to comprehensively and adequately evaluate the safety of phenobarbital for the treatment of epilepsy.
METHODS
The literature was searched using the Cochrane Central Register of randomised controlled trials (1800-2009), Medline (1966-2009), Embase (1966-2009) and three Chinese databases.
RESULTS
Twenty studies were finally included in this systematic review. The determination of adverse effects of combined antiepileptic drugs (AEDs) from different studies was complicated by numerous factors including study design, different descriptions of adverse events and a lack of standardised data collection. These factors may also have been responsible for the heterogeneity present in the meta-analysis. The data did not demonstrate any evidence of association between phenobarbital and a higher risk of adverse events. However, phenobarbital appeared to be associated with a higher rate of adverse drug reaction related withdrawal (ADR-related withdraw), compared to carbamazepine, valproic acid and phenytoin. This may have been due to a concern for possible adverse effects of phenobarbital.
CONCLUSIONS
Phenobarbital was associated with a higher rate of drug withdrawal although there was no evidence to suggest that phenobarbital caused more adverse events compared to carbamazepine, valproic acid or phenytoin. However, in the case of pregnant women, it is important for clinicians to evaluate the benefits and risks of phenobarbital administration before making a final recommendation. Furthermore, unified scales for the assessment of cognitive function should be applied for future studies particularly in children.
Topics: Anticonvulsants; Carbamazepine; Child; Cognition Disorders; Cohort Studies; Cross-Over Studies; Data Collection; Data Interpretation, Statistical; Epilepsy; Female; Humans; Male; Phenobarbital; Phenytoin; Pregnancy; Randomized Controlled Trials as Topic; Research; Research Design; Treatment Outcome; Valproic Acid
PubMed: 21926048
DOI: 10.1684/epd.2011.0444 -
BMJ Clinical Evidence May 2011About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission. (Review)
Review
INTRODUCTION
About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of starting antiepileptic drug treatment following a single seizure? What are the effects of drug monotherapy in people with partial epilepsy? What are the effects of additional drug treatments in people with drug-resistant partial epilepsy? What is the risk of relapse in people in remission when withdrawing antiepileptic drugs? What are the effects of behavioural and psychological treatments for people with epilepsy? What are the effects of surgery in people with drug-resistant temporal lobe epilepsy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 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 83 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiepileptic drugs after a single seizure; monotherapy for partial epilepsy using carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, sodium valproate, or topiramate; addition of second-line drugs for drug-resistant partial epilepsy (allopurinol, eslicarbazepine, gabapentin, lacosamide, lamotrigine, levetiracetam, losigamone, oxcarbazepine, retigabine, tiagabine, topiramate, vigabatrin, or zonisamide); antiepileptic drug withdrawal for people with partial or generalised epilepsy who are in remission; behavioural and psychological treatments for partial or generalised epilepsy (biofeedback, cognitive behavioural therapy (CBT), educational programmes, family counselling, relaxation therapy (alone or plus behavioural modification therapy, yoga); and surgery for drug-resistant temporal lobe epilepsy ( lesionectomy, temporal lobectomy, vagus nerve stimulation as adjunctive therapy).
Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy; Humans; Phenytoin; Vigabatrin
PubMed: 21549021
DOI: No ID Found -
The Cochrane Database of Systematic... Jan 2010Preterm infants are at risk of periventricular haemorrhage. Phenobarbital might prevent ischaemic injury or reduce fluctuations in blood pressure and blood flow in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preterm infants are at risk of periventricular haemorrhage. Phenobarbital might prevent ischaemic injury or reduce fluctuations in blood pressure and blood flow in the brain.
OBJECTIVES
To assess the benefits and harms of giving phenobarbital to women at risk of imminent very preterm birth with the primary aim of preventing periventricular haemorrhage in the infant.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2008).
SELECTION CRITERIA
Randomised trials with reported data that compared neonatal and maternal outcomes following prenatal exposure to phenobarbital, with outcomes in controls with or without placebo.
DATA COLLECTION AND ANALYSIS
We independently assessed trial eligibility and quality and extracted data. We included eligible trials in the initial analysis and prespecified sensitivity analyses to evaluate the effect of trial quality.
MAIN RESULTS
Nine trials (1752 women) were included. Analyses of all included trials showed a significant reduction in the rates of all grades of periventricular haemorrhage (PVH) (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.50 to 0.83; nine trials; 1591 women) and severe grades PVH (3 and 4) (RR 0.41, 95% CI 0.20 to 0.85; eight trials; 1527 women) in infants whose mothers had been given prenatal phenobarbital. These results were influenced by trials of poor quality which contributed excessive weight in the analysis due to their higher rates of severe PVH. When only the two higher quality trials were included, these beneficial effects disappeared for all grades of PVH (RR 0.90, 95% CI 0.75 to 1.08; two trials; 945 women), and severe grades of PVH (RR 1.05, 95% CI 0.60 to 1.83; two trials; 945 women).No difference was found in the incidence of neurodevelopmental abnormalities at paediatric follow up at 18 to 24 months or seven years of age between children born to mothers given prenatal phenobarbital and children not so exposed. Maternal sedation was more likely in women receiving phenobarbital (RR 2.06, 95% CI 1.79 to 2.37; one trial; 576 women).
AUTHORS' CONCLUSIONS
The evidence in this review does not support the use of prophylactic maternal phenobarbital administration to prevent periventricular haemorrhage in preterm infants or to protect them from neurological disability in childhood. Phenobarbital administration may lead to maternal sedation. If any future trials are carried out, they should measure neurodevelopmental status at follow up.
Topics: Central Nervous System Agents; Cerebral Hemorrhage; Cerebral Ventricles; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Obstetric Labor, Premature; Phenobarbital; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 20091502
DOI: 10.1002/14651858.CD000164.pub2 -
BMJ Clinical Evidence Jun 2010About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission. (Review)
Review
INTRODUCTION
About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of monotherapy in newly diagnosed generalised epilepsy (tonic clonic type)? What are the effects of additional treatments in people with drug-resistant generalised epilepsy? What are the effects of surgery in people with drug-resistant generalised epilepsy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 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 eight systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: monotherapy using carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, sodium valproate, or topiramate; addition of second-line drugs (lamotrigine or levetiracetam) for drug-resistant epilepsy; and hemispherectomy for drug-resistant epilepsy.
Topics: Anticonvulsants; Carbamazepine; Epilepsy; Epilepsy, Generalized; Humans; Incidence; Phenytoin; Remission Induction; Valproic Acid
PubMed: 21418687
DOI: No ID Found -
Fetal Diagnosis and Therapy 2009To report a case of maternal Crigler-Najjar syndrome (CNS) type II in pregnancy, systematically review the literature for similar case reports, and to evaluate whether... (Review)
Review
OBJECTIVE
To report a case of maternal Crigler-Najjar syndrome (CNS) type II in pregnancy, systematically review the literature for similar case reports, and to evaluate whether pregnancy is safe in patients with the disease. Data sources included the PubMed and up to date databases.
RESULTS
A 37-year-old mother with CNS type II was treated with phenobarbital during her pregnancy and her bilirubin levels were monitored. Her newborn had mild direct hyperbilirubinemia, did not require any treatment and his postnatal follow-up showed normal growth and development as well as normal hearing.
CONCLUSION
CNS type II is rare, and only a few pregnancies with this condition have been reported. Maternal treatment with phenobarbital lowers the unconjugated bilirubin and avoids fetal and newborn sequelae.
Topics: Adult; Bilirubin; Crigler-Najjar Syndrome; Female; Hearing Disorders; Humans; Infant; Infant, Newborn; Kernicterus; Male; Phenobarbital; Pregnancy; Pregnancy Complications; Pregnancy Outcome
PubMed: 19752526
DOI: 10.1159/000238122 -
Neurology Jul 2009To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy. (Review)
Review
Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and...
OBJECTIVE
To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy.
METHODS
Systematic review of relevant articles published between January 1985 and June 2007.
RESULTS
It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine and possible compared to phenytoin or lamotrigine. Compared to untreated WWE, it is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. It is probable that antiepileptic drug (AED) polytherapy as compared to monotherapy regimens contributes to the development of MCMs and to reduced cognitive outcomes. For monotherapy, intrauterine exposure to VPA probably reduces cognitive outcomes. Further, monotherapy exposure to phenytoin or phenobarbital possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7.
RECOMMENDATIONS
If possible, avoidance of valproate (VPA) and antiepileptic drug (AED) polytherapy during the first trimester of pregnancy should be considered to decrease the risk of major congenital malformations (Level B). If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered to prevent reduced cognitive outcomes (Level B). If possible, avoidance of phenytoin and phenobarbital during pregnancy may be considered to prevent reduced cognitive outcomes (Level C). Pregnancy risk stratification should reflect that the offspring of women with epilepsy taking AEDs are probably at increased risk for being small for gestational age (Level B) and possibly at increased risk of 1-minute Apgar scores of <7 (Level C).
Topics: Abnormalities, Drug-Induced; Anticonvulsants; Birth Weight; Cognition Disorders; Contraindications; Drug Therapy, Combination; Epilepsy; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Risk; Valproic Acid
PubMed: 19398681
DOI: 10.1212/WNL.0b013e3181a6b312 -
The Cochrane Database of Systematic... Apr 2008Seizures can present at any time before or after diagnosis of a brain tumor. The risk of seizures varies by tumor type and its location in the brain. For a long time we... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Seizures can present at any time before or after diagnosis of a brain tumor. The risk of seizures varies by tumor type and its location in the brain. For a long time we believed that preventing seizures with antiepileptic drugs (seizure prophylaxis) was effective and necessary, but the supporting evidence was little and mixed. Such evidence was the basis for previous reviews to conclude that seizure prophylaxis was ineffective in people with brain tumors.
OBJECTIVES
To estimate the effectiveness of seizure prophylaxis in people with brain tumors, and to estimate the adverse event rates in the identified clinical trials.
SEARCH STRATEGY
A search strategy that included free-text and MeSH terms in LILACS, EMBASE, PubMed, CENTRAL, and The Cochrane Library (1966 to 2007).
SELECTION CRITERIA
Controlled clinical trials with random allocation, blinded or unblinded, and placebo or observation in the control groups.
DATA COLLECTION AND ANALYSIS
We screened the articles, extracted the data, and rated the validity of each trial to assess the risk of bias. Our primary outcome was the occurrence of a first seizure. The secondary outcome was adverse events. We pooled the aggregate data for each outcome into a random-effects model meta-analysis using the relative risk (RR). For adverse events, we also included the number needed to harm (NNH) using the absolute risk increase to compute the NNH.
MAIN RESULTS
There was no difference between the treatment interventions and the control groups in preventing a first seizure in participants with brain tumors. The risk of an adverse event was higher for those on antiepileptic drugs than for participants not on antiepileptic drugs (NNH 3; RR 6.10, 95% CI 1.10 to 34.63; P = 0.046).
AUTHORS' CONCLUSIONS
The evidence is neutral, neither for nor against seizure prophylaxis, in people with brain tumors. These conclusions apply only for the antiepileptic drugs phenytoin, phenobarbital, and divalproex sodium. The decision to start an antiepileptic drug for seizure prophylaxis is ultimately guided by assessment of individual risk factors and careful discussion with patients.
Topics: Anticonvulsants; Brain Neoplasms; Humans; Seizures
PubMed: 18425902
DOI: 10.1002/14651858.CD004424.pub2 -
The Cochrane Database of Systematic... Apr 2007Neonates from isoimmunized pregnancies have increased morbidity from neonatal jaundice. The increased bilirubin from haemolysis often needs phototherapy, exchange... (Review)
Review
BACKGROUND
Neonates from isoimmunized pregnancies have increased morbidity from neonatal jaundice. The increased bilirubin from haemolysis often needs phototherapy, exchange transfusion or both after birth. Various trials in pregnant women who were not isoimmunized but had other risk factors for neonatal jaundice have shown a reduction in need for phototherapy and exchange transfusion by the use of antenatal phenobarbital. A recent retrospective case-controlled study showed reduction in the need for exchange transfusion for the neonates from isoimmunized pregnancies.
OBJECTIVES
To assess the effects of antenatal phenobarbital in red cell isoimmunized pregnancies in reducing the incidence of phototherapy and exchange transfusion for the neonate.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (June 2006).
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials of pregnant women established to have red cell isoimmunization in the current pregnancy during their antenatal testing and given phenobarbital alone or in combination with other drugs before birth.
DATA COLLECTION AND ANALYSIS
All three review authors independently assessed study eligibility and quality.
MAIN RESULTS
No trials met the inclusion criteria for this review.
AUTHORS' CONCLUSIONS
The use of antenatal phenobarbital to reduce neonatal jaundice in red cell isoimmunized pregnant women has not been evaluated in randomised controlled trials.
Topics: Excitatory Amino Acid Antagonists; Female; Humans; Infant, Newborn; Jaundice, Neonatal; Phenobarbital; Pregnancy; Prenatal Care; Rh Isoimmunization
PubMed: 17443599
DOI: 10.1002/14651858.CD005541.pub2 -
Paediatric and Perinatal Drug Therapy May 2006INTRODUCTION: Against a background of concern about the safety of new pharmaceutical products, there has been renewed interest in one of the oldest antiepileptic drugs...
INTRODUCTION: Against a background of concern about the safety of new pharmaceutical products, there has been renewed interest in one of the oldest antiepileptic drugs (AEDs), phenobarbital. Although still in widespread use in developing countries, its popularity has slipped in Western countries over the past century, partly because of controversy about its adverse effect profile. This critical review examines the evidence supporting its effectiveness and its associated behavioural adverse effects for febrile convulsions and childhood epilepsy. METHODS: Relevant randomised controlled trials (RCTs) of phenobarbital vs other antiepileptic drugs or placebo between 1970-2005 were identified through a comprehensive manual and computer database search of the world biomedical literature. Eleven RCTs of febrile convulsions and nine RCTs of childhood epilepsy were systematically reviewed against a conventional set of quality criteria. RESULTS: With a few exceptions, the overall quality of clinical trial methodology, especially in the early studies conducted in the 1970s and 1980s, was poor. There is no evidence for a difference in antiepileptic efficacy between phenobarbital and any other compared AED, yet no evidence for absolute efficacy. No convincing evidence exists for an excess of behavioural adverse effects, over other AEDs, attributable to phenobarbital. Masked studies of phenobarbital in childhood epilepsy have shown no significant differences in behavioural or cognitive adverse effects compared to other AEDs. This is in contrast to the excess of such adverse effects reported in studies open to observer bias. However, the one finding of reduction in cognitive ability associated with phenobarbital treatment for febrile convulsions remains a concern. Future areas of clinical and genetic epidemiological research are outlined.
PubMed: 17356688
DOI: 10.1185/146300905X75361 -
The Cochrane Database of Systematic... Jan 2007The aim of drug treatment for epilepsy is to prevent seizures without causing adverse effects. To achieve this, drug dosages need to be individualised. Measuring... (Review)
Review
BACKGROUND
The aim of drug treatment for epilepsy is to prevent seizures without causing adverse effects. To achieve this, drug dosages need to be individualised. Measuring antiepileptic drug levels in body fluids (therapeutic drug monitoring) is frequently used to optimise drug dosage for individual patients.
OBJECTIVES
To review the evidence regarding the effects of therapeutic drug monitoring upon outcomes in epilepsy.
SEARCH STRATEGY
We searched the Cochrane Epilepsy Group Specialised Register (September 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2005, Issue 4), MEDLINE (January 1966 to April 2005) and EMBASE (1974 to May 2005). No language restrictions were imposed. We checked the reference lists of retrieved articles for additional reports of relevant studies.
SELECTION CRITERIA
Randomised controlled trials comparing the outcomes of antiepileptic drug monotherapy guided by therapeutic drug monitoring with drug treatment without the aid of therapeutic drug monitoring.
DATA COLLECTION AND ANALYSIS
We based this review on published aggregate data. The main outcomes measured were the proportions of patients achieving a 12-month remission from seizures, reporting adverse effects, and being withdrawn from the treatment they had been randomised to receive.
MAIN RESULTS
Only one study met the inclusion criteria for the review. In this open study, 180 patients with newly-diagnosed, untreated epilepsy were randomised to treatment with the antiepileptic drug selected by their physician either with or without therapeutic drug serum level monitoring as an aid to dosage adjustments. The antiepileptic drugs used were carbamazepine, valproate, phenytoin, phenobarbital and primidone. A 12-month remission from seizures was achieved by 60% of the patients randomised to therapeutic drug monitoring (intervention group) and by 61% in the control group. A total of 56% in the intervention group and 58% in the control group were seizure free during the last 12 months of follow up. Adverse effects were reported by 48% in the intervention group and 47% of the control group patients. Of those randomised to therapeutic drug monitoring, 62% completed the two-year follow up compared with 67% of the control group.
AUTHORS' CONCLUSIONS
We found no clear evidence to support routine antiepileptic drug serum concentration measurement with the aim of reaching predefined target ranges for the optimisation of treatment of patients with newly-diagnosed epilepsy with antiepileptic drug monotherapy. However, this does not exclude the possible usefulness of therapeutic drug monitoring of specific antiepileptic drugs during polytherapy, in special situations or in selected patients, although evidence is lacking.
Topics: Anticonvulsants; Carbamazepine; Drug Monitoring; Epilepsy; Humans; Phenobarbital; Phenytoin; Primidone; Valproic Acid
PubMed: 17253477
DOI: 10.1002/14651858.CD002216.pub2