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BMC Veterinary Research Oct 2014Various antiepileptic drugs (AEDs) are used for the management of canine idiopathic epilepsy (IE). Information on their clinical efficacy remains limited. A systematic... (Review)
Review
BACKGROUND
Various antiepileptic drugs (AEDs) are used for the management of canine idiopathic epilepsy (IE). Information on their clinical efficacy remains limited. A systematic review was designed to evaluate existing evidence for the effectiveness of AEDs for presumptive canine IE. Electronic searches of PubMed and CAB Direct were carried out without date or language restrictions. Conference proceedings were also searched. Peer-reviewed full-length studies describing objectively the efficacy of AEDs in dogs with IE were included. Studies were allocated in two groups, i.e. blinded randomized clinical trials (bRCTs), non-blinded randomized clinical trials (nbRCTs) and non-randomized clinical trials (NRCTs) (group A) and uncontrolled clinical trials (UCTs) and case series (group B). Individual studies were evaluated based on the quality of evidence (study design, study group sizes, subject enrolment quality and overall risk of bias) and the outcome measures reported (in particular the proportion of dogs with ≥ 50% reduction in seizure frequency).
RESULTS
Twenty-six studies, including two conference proceedings, reporting clinical outcomes of AEDs used for management of IE were identified. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. Only four bRCTs were identified in group A and were considered to offer higher quality of evidence among the studies. A good level of evidence supported the efficacy of oral phenobarbital and imepitoin and fair level of evidence supported the efficacy of oral potassium bromide and levetiracetam. For the remaining AEDs, favorable results were reported regarding their efficacy, but there was insufficient evidence to support their use due to lack of bRCTs.
CONCLUSIONS
Oral phenobarbital and imepitoin in particular, as well as potassium bromide and levetiracetam are likely to be effective for the treatment of IE. However, variations in baseline characteristics of the dogs involved, significant differences between study designs and several potential sources of bias preclude definitive recommendations. There is a need for greater numbers of adequately sized bRCTs evaluating the efficacy of AEDs for IE.
Topics: Animals; Anticonvulsants; Dog Diseases; Dogs; Epilepsy
PubMed: 25338624
DOI: 10.1186/s12917-014-0257-9 -
The Cochrane Database of Systematic... Sep 2014Status epilepticus is a medical emergency associated with significant mortality and morbidity that requires immediate and effective treatment. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Status epilepticus is a medical emergency associated with significant mortality and morbidity that requires immediate and effective treatment.
OBJECTIVES
(1) To determine whether a particular anticonvulsant is more effective or safer to use in status epilepticus compared to another and compared to placebo.(2) To delineate reasons for disagreement in the literature regarding recommended treatment regimens and to highlight areas for future research.
SEARCH METHODS
For the latest update of this review, the following electronic databases were searched on 15/08/2013: the Cochrane Epilepsy Group's Specialized Register, CENTRAL The Cochrane Library July 2013, Issue 7, and MEDLINE (Ovid) 1946 to 15/08/2013.
SELECTION CRITERIA
Randomised controlled trials of participants with premonitory, early, established or refractory status epilepticus using a truly random or quasi-random allocation of treatments were included.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, assessed trial quality and extracted data.
MAIN RESULTS
Eighteen studies with 2755 participants were included. Few studies used the same interventions. Intravenous diazepam was better than placebo in reducing the risk of non-cessation of seizures (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.57 to 0.92), requirement for ventilatory support (RR 0.39, 95% CI 0.16 to 0.94), or continuation of status epilepticus requiring use of a different drug or general anaesthesia (RR 0.73, 95% CI 0.57 to 0.92). Intravenous lorazepam was better than placebo for risk of non-cessation of seizures (RR 0.52, 95% CI 0.38 to 0.71) and for risk of continuation of status epilepticus requiring a different drug or general anaesthesia (RR 0.52, 95% CI 0.38 to 0.71). Intravenous lorazepam was better than intravenous diazepam for reducing the risk of non-cessation of seizures (RR 0.64, 95% CI 0.45 to 0.90) and had a lower risk for continuation of status epilepticus requiring a different drug or general anaesthesia (RR 0.63, 95% CI 0.45 to 0.88). Intravenous lorazepam was better than intravenous phenytoin for risk of non-cessation of seizures (RR 0.62, 95% CI 0.45 to 0.86). Diazepam gel was better than placebo gel in reducing the risk of non-cessation of seizures (RR 0.43 95% CI 0.30 to 0.62)For pre-hospital treatment, intramuscular midazolam is at least as effective as (probably more effective than) intravenous lorazepam in control of seizures (RR1.16, 95% CI 1.06 to 1.27) and frequency of hospitalisation (RR 0.88, 95% CI 0.79 to 0.97) or intensive care admissions (RR 0.79, 95% CI 0.65 to 0.96). It was uncertain whether Intravenous valproate was better than intravenous phenytoin in reducing risk of non-cessation of seizures (RR 0.75, 95% CI 0.28 to 2.00). Both levetiracetam and lorazepam were equally effective in aborting seizures (RR 0.97, 95% CI 0.44 to 2.13). Results for other comparisons of anticonvulsant therapies were uncertain due to single studies with few participants.The body of randomised evidence to guide clinical decisions is small. It was uncertain whether any anticonvulsant therapy was better than another in terms of adverse effects, due to few studies and participants identified. The quality of the evidence from the included studies is not strong but appears acceptable. We were unable to make judgements for risk of bias domains incomplete outcome reporting (attrition bias) and selective outcome reporting (selection bias) due to unclear reporting by the study authors.
AUTHORS' CONCLUSIONS
Intravenous lorazepam is better than intravenous diazepam or intravenous phenytoin alone for cessation of seizures. Intravenous lorazepam also carries a lower risk of continuation of status epilepticus requiring a different drug or general anaesthesia compared with intravenous diazepam. Both intravenous lorazepam and diazepam are better than placebo for the same outcomes. For pre hospital management, midazolam IM seemed more effective than lorazepam IV for cessation of seizures, frequency of hospitalisation and ICU admissions however,it was unclear whether the risk of recurrence of seizures differed between treatments. The results of other comparisons of anticonvulsant therapies versus each other were also uncertain. Universally accepted definitions of premonitory, early, established and refractory status epilepticus are required. Diazepam gel was better than placebo gel in reducing the risk of non-cessation of seizures. Results for other comparisons of anticonvulsant therapies were uncertain due to single studies with few participants.
Topics: Anticonvulsants; Diazepam; Humans; Injections, Intravenous; Lorazepam; Midazolam; Phenobarbital; Phenytoin; Randomized Controlled Trials as Topic; Status Epilepticus
PubMed: 25207925
DOI: 10.1002/14651858.CD003723.pub3 -
Addiction Science & Clinical Practice Sep 2014Neonatal abstinence syndrome (NAS) secondary to in-utero opioid exposure is an increasing problem. Variability in assessment and treatment of NAS has been attributed to... (Review)
Review
Neonatal abstinence syndrome (NAS) secondary to in-utero opioid exposure is an increasing problem. Variability in assessment and treatment of NAS has been attributed to the lack of high-quality evidence to guide management of exposed neonates. This systematic review examines available evidence for NAS assessment tools, nonpharmacologic interventions, and pharmacologic management of opioid-exposed infants. There is limited data on the inter-observer reliability of NAS assessment tools due to lack of a standardized approach. In addition, most scales were developed prior to the prevalent use of prescribed prenatal concomitant medications, which can complicate NAS assessment. Nonpharmacologic interventions, particularly breastfeeding, may decrease NAS severity. Opioid medications such as morphine or methadone are recommended as first-line therapy, with phenobarbital or clonidine as second-line adjunctive therapy. Further research is needed to determine best practices for assessment, nonpharmacologic intervention, and pharmacologic management of infants with NAS in order to improve outcomes.
Topics: Breast Feeding; Buprenorphine; Clonidine; Female; Humans; Infant, Newborn; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects
PubMed: 25199822
DOI: 10.1186/1940-0640-9-19 -
The Cochrane Database of Systematic... Mar 2014This review has been withdrawn as the original review author team are unable to update the review. We hope to reallocate to another review author team in the near... (Meta-Analysis)
Meta-Analysis Review
This review has been withdrawn as the original review author team are unable to update the review. We hope to reallocate to another review author team in the near future. The editorial group responsible for this previously published document have withdrawn it from publication.
Topics: Anticonvulsants; Drugs, Chinese Herbal; Epilepsy; Epilepsy, Tonic-Clonic; Humans; Medicine, Chinese Traditional; Phenobarbital; Phenytoin; Randomized Controlled Trials as Topic; Valproic Acid
PubMed: 24619450
DOI: 10.1002/14651858.CD006454.pub3 -
The Cochrane Database of Systematic... Aug 2013Intraventricular haemorrhage (IVH) is a major complication of preterm birth. Large haemorrhages are associated with a high risk of disability and hydrocephalus.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intraventricular haemorrhage (IVH) is a major complication of preterm birth. Large haemorrhages are associated with a high risk of disability and hydrocephalus. Instability of blood pressure and cerebral blood flow are postulated as causative factors. Another mechanism may involve reperfusion damage from oxygen free radicals. Phenobarbital has been suggested as a safe treatment that stabilises blood pressure and may protect against free radicals.
OBJECTIVES
To determine the effect of postnatal administration of phenobarbital on the risk of IVH, neurodevelopmental impairment or death in preterm infants.
SEARCH METHODS
We used the search strategy of the Neonatal Collaborative Review Group. The original review author (A Whitelaw) was an active trialist in this area and had personal contact with many groups in this field. He handsearched journals from 1976 (when cranial computed tomography (CT) scanning started) to October 2000; these included: Pediatrics, Journal of Pediatrics, Archives of Disease in Childhood, Pediatric Research, Developmental Medicine and Child Neurology, Acta Paediatrica, European Journal of Pediatrics, Neuropediatrics, New England Journal of Medicine, Lancet and British Medical Journal. We searched the National Library of Medicine (USA) database (via PubMed) and the Cochrane Central Register of Controlled Trials (CENTRAL, 2012, Issue 10) through to 31 October 2012. We did not limit the searches to the English language, as long as the article included an English abstract. We read identified articles in the original language or translated.
SELECTION CRITERIA
We included randomised or quasi-randomised controlled trials in which phenobarbital was given to preterm infants identified as being at risk of IVH because of gestational age below 34 weeks, birthweight below 1500 g or respiratory failure. Adequate determination of IVH by ultrasound or CT was also required.
DATA COLLECTION AND ANALYSIS
In addition to details of patient selection and control of bias, we extracted the details of the administration of phenobarbital. We searched for the following endpoints: IVH (with grading), posthaemorrhagic ventricular dilation or hydrocephalus, neurodevelopmental impairment and death. In addition, we searched for possible adverse effects of phenobarbitone, for example hypotension, mechanical ventilation, pneumothorax, hypercapnia and acidosis.
MAIN RESULTS
We included 12 controlled trials that recruited 982 infants. There was heterogeneity between trials for the outcome IVH, with three trials finding a significant decrease in IVH and one trial finding an increase in IVH in the group receiving phenobarbital. Meta-analysis showed no difference between the phenobarbital-treated group and the control group in either all IVH (typical risk ratio (RR) 0.91; 95% CI 0.77 to 1.08), severe IVH (typical RR 0.77; 95% CI 0.58 to 1.04), posthaemorrhagic ventricular dilation (typical RR 0.89; 95% CI 0.38 to 2.08), severe neurodevelopmental impairment (typical RR 1.44; 95% CI 0.41 to 5.04) or death before hospital discharge (typical RR 0.88; 95% CI 0.64 to 1.21). There was a consistent trend in the trials towards increased use of mechanical ventilation in the phenobarbital-treated group, which was supported by the meta-analysis (typical RR 1.18; 95% CI 1.06 to 1.32; typical risk difference 0.129; 95% CI 0.04 to 0.21), but there was no significant difference in pneumothorax, acidosis or hypercapnia.
AUTHORS' CONCLUSIONS
Postnatal administration of phenobarbital cannot be recommended as prophylaxis to prevent IVH in preterm infants and is associated with an increased need for mechanical ventilation.
Topics: Cerebral Hemorrhage; Cerebral Ventricles; Excitatory Amino Acid Antagonists; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Phenobarbital; Randomized Controlled Trials as Topic
PubMed: 23943189
DOI: 10.1002/14651858.CD001691.pub3 -
CNS Drugs Apr 2013Partial-onset seizures contribute the bulk of seizure burden in childhood epilepsy. The therapeutic decision making involves consideration of factors specific to drug,... (Review)
Review
BACKGROUND
Partial-onset seizures contribute the bulk of seizure burden in childhood epilepsy. The therapeutic decision making involves consideration of factors specific to drug, patient and socioeconomic situation.
OBJECTIVES
This paper systematically reviews the available efficacy/effectiveness evidence for various anti-epileptic drugs (AED) as monotherapy and adjunctive therapy for partial-onset seizures in children.
DATA SOURCES
Relevant randomized clinical trials (RCTs) were identified by a structured PubMed search, supplemented by an additional hand search of reference lists and authors' files.
STUDY APPRAISAL AND SYNTHESIS METHODS
Eligible studies were reviewed and data extracted into tables. Included RCTs were classified based on accepted published criteria.
OUTCOMES
Only efficacy and effectiveness outcome measures were evaluated since there is little scientifically rigorous comprehensive AED adverse effects data.
RESULTS
Oxcarbazepine is the only AED with Class I evidence for efficacy/effectiveness as initial monotherapy for partial-onset seizures in children. Carbamazepine, clobazam, lamotrigine, phenobarbital, phenytoin, topiramate, valproate, vigabatrin and zonisamide have, at best, Class III efficacy/effectiveness evidence for monotherapy of partial-onset seizures in children. For adjunctive therapy, gabapentin, lamotrigine, levetiracetam, oxcarbazepine and topiramate have Class I efficacy/effectiveness evidence for treatment of pediatric partial-onset seizures.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
This efficacy/effectiveness analysis must not be used in isolation when selecting therapy. AED selection for a specific child needs to integrate a drug's efficacy/effectiveness data with its safety and tolerability profile, pharmacokinetic properties, available formulations, and patient specific characteristics. It is critical that physicians and patients incorporate all these relevant variables when choosing AED therapy.
Topics: Anticonvulsants; Child; Decision Making; Drug Approval; Epilepsies, Partial; Humans; Randomized Controlled Trials as Topic; Socioeconomic Factors; Treatment Outcome
PubMed: 23515971
DOI: 10.1007/s40263-013-0048-z -
Epilepsia Dec 2012This article reviews the current position of phenobarbital using articles published since 2000 and speculates on its likely future contribution to epilepsy care. Over... (Review)
Review
This article reviews the current position of phenobarbital using articles published since 2000 and speculates on its likely future contribution to epilepsy care. Over the last decade there have been no major double-blind randomized placebo-controlled or comparative trials with phenobarbital. Previous studies have suggested that phenobarbital is as effective in monotherapy as phenytoin and carbamazepine. Several observational studies undertaken in developing countries over the last decade have confirmed its efficacy and safety for the common epilepsies. This was particularly so in the substantial demonstration project undertaken in rural China under the auspices of the World Health Organization in partnership with the International League Against Epilepsy and International Bureau for Epilepsy. Phenobarbital is still widely used for neonatal and childhood seizures and for drug-resistant convulsive and nonconvulsive status epilepticus. Recent data have confirmed in a prospective cohort of women taking phenobarbital as monotherapy that the drug can be associated with a range of congenital defects in exposed infants. Much effort has gone into exploring the apparent contradiction of higher withdrawal rates due to cognitive and behavioral side effects in studies undertaken in developed countries but not in those sited in the developing world. A raft of data over the last 10 years, including a systematic review, showed no important differences between the tolerability of phenobarbital compared to that with other antiepileptic drugs. Finally, cognitive test scores and mood ratings in 136 people with epilepsy receiving phenobarbital for a year were similar to those in 137 age-, sex-, and education-matched controls in a number of Chinese villages. Indeed, there were some cognitive gains in the patients possibly due to improved seizure control. Phenobarbital is still the most cost-effective pharmacologic treatment for epilepsy. All these data predict a healthy future for phenobarbital, particularly in helping to close the treatment gap in low- and middle-income countries during its second century of clinical use.
Topics: Anticonvulsants; China; Epilepsy; Forecasting; Humans; Phenobarbital; Randomized Controlled Trials as Topic
PubMed: 23205961
DOI: 10.1111/epi.12027 -
The Journal of Pediatric Pharmacology... Jan 2012Neonatal seizures are associated with neurological sequelae and an increased risk of epilepsy later in life. Phenobarbital and phenytoin remain the antiepileptic drugs...
BACKGROUND
Neonatal seizures are associated with neurological sequelae and an increased risk of epilepsy later in life. Phenobarbital and phenytoin remain the antiepileptic drugs (AEDs) most commonly used to treat neonatal seizures, despite their suboptimal effectiveness and safety. As a result, other AEDs, such as levetiracetam and topiramate, are often used in neonates with refractory seizures, despite limited data and off-label use.
OBJECTIVES
To systematically review published pharmacokinetic data for second-line AEDs used in neonates with seizures and to provide dosing recommendations for these agents in the neonatal population.
METHODS
A literature search was conducted in PubMed (1949-May 2012), Medline (1950-May 2012), and Embase (1980-May 2012). Each study was ranked according to the quality of evidence it provided, based on the classification system developed by the US Preventive Services Task Force. Information extracted from each study included study design, number of subjects, gestational and postnatal age, AED dosage regimen, pharmacokinetic parameters, pharmacokinetic model, AED serum concentrations, and sampling times.
RESULTS
Nineteen relevant pharmacokinetic studies involving a total of 8 different drugs were identified. No prospective, randomized, controlled studies (level I evidence) or nonrandomized controlled studies (level II-I evidence) were identified; 2 studies were prospective, nonrandomized, uncontrolled (cohort) studies (level II-2 evidence), 11 studies obtained evidence from multiple time series (level II-3 evidence), and 6 studies were case reports or descriptive studies (level III evidence).
CONCLUSIONS
There are limited pharmacokinetic data for the use of carbamazepine, levetiracetam, lidocaine, paraldehyde, topiramate, valproic acid, and vigabatrin for neonates with seizures refractory to treatment with first-line antiepileptic agents. Further research is needed to elucidate target AED serum concentrations (if any) required to optimize effectiveness and minimize dose-related adverse effects in neonates.
PubMed: 23118657
DOI: 10.5863/1551-6776-17.1.31 -
BMJ Clinical Evidence Feb 2012About 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 August 2011 (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 8 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: 22348419
DOI: No ID Found -
Journal (Canadian Dental Association) 2011Long-term use of phenytoin (PHT) causes gingival hyperplasia; however, little is known about the oral side effects of other antiepileptic drugs (AEDs). Through a... (Review)
Review
OBJECTIVE
Long-term use of phenytoin (PHT) causes gingival hyperplasia; however, little is known about the oral side effects of other antiepileptic drugs (AEDs). Through a systematic review of the literature, we explored the effects of AEDs on the oral health of patients with epilepsy.
METHODS
We searched PubMed, EMBASE and the Cochrane library between January 1963 and August 2010. The search strategy retrieved 170 abstracts. We included studies that involved original research and had ≥ 10 patients in our review. We also checked the reference lists of reviews, letters and other manuscripts to find studies that met our selection criteria.
RESULTS
Only 15 articles were included in the final analysis. Gingival hyperplasia was very common in patients taking PHT (16%-94% of patients). Alveolar bone loss occurred in patients taking carbamazepine or PHT. Patients taking valproate, carbamazepine or phenobarbital also had gingival hyperplasia. We found no published studies of newer-generation AEDs.
CONCLUSION
Although several studies examined the effects of PHT on oral health, none have studied those of the newer generation of AEDs. Studies exploring oral side effects of AEDs are needed.
Topics: Alveolar Bone Loss; Anticonvulsants; Carbamazepine; Epilepsy; Gingival Hyperplasia; Humans; Oral Health; Phenobarbital; Phenytoin
PubMed: 22260801
DOI: No ID Found