Drug treatment of neonatal seizures by neonatologists and paediatric neurologists

Carmo, Kathryn Browning; Barr, Peter

doi:10.1111/j.1440-1754.2005.00638.x

Cited by 37 publications

(31 citation statements)

References 21 publications

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“…11 An Australian study found that neonatologists were more likely to stop antiepileptic drugs within a few days of seizure cessation than neurologists (89% vs 56%). 3 These findings emphasize the need for further studies to determine the optimal length of treatment after neonatal seizures cease given the potential deleterious effects of antiepileptic drug treatment and seizure recurrence in the critical neonatal period.…”

Section: Discussionmentioning

confidence: 94%

Neonatal Seizures: Treatment and Treatment Variability in 31 United States Pediatric Hospitals

2009

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Neonatal seizures are one of the most common neurological disorders in infants. However, the optimal treatment strategy for neonatal seizures remains controversial and there is little data regarding current treatment of neonatal seizures. In this study we describe the current treatment of neonatal seizures and variation in practice among 31 pediatric hospitals in the United States. We retrospectively identified 6099 infants hospitalized in the first month of life in one of 31 pediatric hospitals participating in the Pediatric Health Information System, with a discharge diagnosis of seizure. As expected, most treated infants received phenobarbital. However, there was significant interhospital variability for all treatments studied including any antiepileptic drug treatment, phenytoin treatment, antiepileptic drug treatment through discharge, number of antiepileptic drugs used, and treatment with pyridoxine (P < .001). These findings highlight the need for rigorous controlled outcome studies to determine optimal therapy for neonatal seizures and devise treatment standards.

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Section: Discussionmentioning

confidence: 94%

Neonatal Seizures: Treatment and Treatment Variability in 31 United States Pediatric Hospitals

2009

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“…On the basis of the simple BSA conversion method, a dose of phenobarbital between 200 and 250 mg/kg in mice, which has the ability to persistently induce the P450 gene expression, can be converted to a human equivalent dose between 15 and 20 mg/kg. This dose is equivalent to a loading dose of phenobarbital used to quickly produce blood levels to approximately 20 mg/ml for optimal anticonvulsant effects in the Food and Drug Administration's dose guidance for treatment of neonatal seizure by phenobarbital (Carmo and Barr, 2005;Lee et al, 2012). However, in a clinical application, using the BSA conversion from an animal species to human is inappropriate in many cases.…”

Section: Discussionmentioning

confidence: 99%

“…The Food and Drug Administration has a dose guidance to manage seizure with phenobarbital in neonates and infants. To quickly produce blood levels to approximate 20 mg/ml for optimal anticonvulsant effects, a much higher loading dose between 15 and 20 mg/kg is given by intravenous injection before a lower maintenance dose between 3 and 6 mg/kg/day is applied (Carmo and Barr, 2005;Lee et al, 2012). This has promoted us to reevaluate Dr. Shapiro's original studies in the context of a phenobarbital dosing regimen that is consistent with its clinical use in early life.…”

Section: Introductionmentioning

confidence: 99%

Dose of Phenobarbital and Age of Treatment at Early Life are Two Key Factors for the Persistent Induction of Cytochrome P450 Enzymes in Adult Mouse Liver

et al. 2015

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Drug treatment of neonates and infants and its long-term consequences on drug responses have emerged in recent years as a major challenge for health care professionals. In the current study, we use phenobarbital as a model drug and mouse as an in vivo model to demonstrate that the dose of phenobarbital and age of treatment are two key factors for the persistent induction of gene expression and consequential increases of enzyme activities of Cyp2b, Cyp2c, and Cyp3a in adult livers. We show that phenobarbital treatment at early life of day 5 after birth with a low dose (<100 mg/kg) does not change expression and enzyme activities of Cyp2b, Cyp2c, and Cyp3a in adult mouse liver, whereas phenobarbital treatment with a high dose (>200 mg/kg) significantly increases expression and enzyme activities of these P450s in adult liver. We also demonstrate that phenobarbital treatment before day 10 after birth, but not at later ages, significantly increases mRNAs, proteins, and enzyme activities of the tested P450s. Such persistent induction of P450 gene expression and enzyme activities in adult livers by phenobarbital treatment only occurs within a sensitive age window early in life. The persistent induction in gene expression and enzyme activities is higher in female mice than in male mice for Cyp2b10 but not for Cyp2c29 and Cyp3a11. These results will stimulate studies to evaluate the long-term impacts of drug treatment with different doses at neonatal and infant ages on drug metabolism, therapeutic efficacy, and drug-induced toxicity throughout the rest of life.

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“…Clearly, these and other differences related to brain maturation might impact on the effect of antiepileptic drugs. Physicians continue to favor older AEDs to treat neonatal seizures, with phenobarbital being the drug of choice, followed by phenytoin and then benzodiazepines (3). Several of these choices (phenobarbital and the benzodiazepines) work by GABA mechanisms.…”

Section: Differences In Underlying Brain Functionmentioning

confidence: 99%

AED Treatment through Different Ages: As Our Brains Change, Should Our Drug Choices Also?

French

Staley

2012

Epilepsy Curr

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The management of epilepsy can be difficult owing to the inherently complex nature of the disorder. Pharmacotherapy with antiepileptic drugs (AEDs) is the most common treatment approach. Thirteen new AEDs have been approved by the FDA since 1993. The increase in available drugs provides more options for the prescribing physician, but it has also increased the complexity of drug selection. Determining which of the many AEDs is the best "fit" for a patient can be a challenge. It is increasingly taught that AED selection can be "personalized, " based on patient characteristics such as age, gender, and the presence of comorbidities. These patient characteristics may be related to the efficacy, safety, and tolerability of AEDs and can help determine the most appropriate drug therapy for an individual.In this review, we focus on age as a factor in selecting the most appropriate AED. There are a number of reasons why age may be a factor in AED selection. Most physicians are aware that many seizure types and syndromes have specific ages of onset, and because many AEDs are more effective for subsets of seizure types and syndromes, some drugs will be more appropriate for individuals of certain ages. For example, ethosuximide, is a drug used to treat absence seizures, a seizure type found most commonly in children and adolescents. This issue will not be discussed further, as it relates more to drug selection based on seizure type. But there may also be other issues that make some drugs more or less appropriate or useful at different ages, even if the seizure type and syndrome are the same. It is these issues that will be discussed in the current review. Examples include changes in brain function at different ages, changes in underlying epilepsy etiology, changes in pharmacokinetics, and changes in frequency and types of adverse effects. There is a great need for data regarding AED efficacy relative to age from randomized control trials (RCTs) to guide clinical decision-making, but these types of studies are few. Until those studies are completed, clinicians may give consideration to patient age when determining a treatment plan for epilepsy, but there will be a paucity of scientifically rigorous data to guide them. Differences in Underlying Brain FunctionHow does the brain differ at different ages, and how can those differences impact drug selection? In newborn infants, seizures are different that those seen at later ages, both semiologically and possibly in regards to underlying pathophysiology and development of neurotransmission. Seizures can present as focal or migrating and multifocal (1) and may be subtle and fragmented. The circuitry in the immature brain is different. The infant brain shows an overdevelopment of excitatory neurotransmission, and a relative underdevelopment of inhibitory transmission. Moreover, even the traditional neurotransmitter GABA may behave differently in the neonatal brain, activating excitatory rather than inhibitory pathways (2). Clearly, these and other differences related to brain matura...

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Drug treatment of neonatal seizures by neonatologists and paediatric neurologists

Cited by 37 publications

References 21 publications

Neonatal Seizures: Treatment and Treatment Variability in 31 United States Pediatric Hospitals

Neonatal Seizures: Treatment and Treatment Variability in 31 United States Pediatric Hospitals

Dose of Phenobarbital and Age of Treatment at Early Life are Two Key Factors for the Persistent Induction of Cytochrome P450 Enzymes in Adult Mouse Liver

AED Treatment through Different Ages: As Our Brains Change, Should Our Drug Choices Also?

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