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The Cochrane Database of Systematic... Aug 2023Prenatal exposure to certain anti-seizure medications (ASMs) is associated with an increased risk of major congenital malformations (MCM). The majority of women with... (Review)
Review
BACKGROUND
Prenatal exposure to certain anti-seizure medications (ASMs) is associated with an increased risk of major congenital malformations (MCM). The majority of women with epilepsy continue taking ASMs throughout pregnancy and, therefore, information on the potential risks associated with ASM treatment is required.
OBJECTIVES
To assess the effects of prenatal exposure to ASMs on the prevalence of MCM in the child.
SEARCH METHODS
For the latest update of this review, we searched the following databases on 17 February 2022: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to February 16, 2022), SCOPUS (1823 onwards), and ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP). No language restrictions were imposed.
SELECTION CRITERIA
We included prospective cohort controlled studies, cohort studies set within pregnancy registries, randomised controlled trials and epidemiological studies using routine health record data. Participants were women with epilepsy taking ASMs; the two control groups were women without epilepsy and untreated women with epilepsy.
DATA COLLECTION AND ANALYSIS
Five authors independently selected studies for inclusion. Eight authors completed data extraction and/or risk of bias assessments. The primary outcome was the presence of an MCM. Secondary outcomes included specific types of MCM. Where meta-analysis was not possible, we reviewed included studies narratively.
MAIN RESULTS
From 12,296 abstracts, we reviewed 283 full-text publications which identified 49 studies with 128 publications between them. Data from ASM-exposed pregnancies were more numerous for prospective cohort studies (n = 17,963), than data currently available for epidemiological health record studies (n = 7913). The MCM risk for children of women without epilepsy was 2.1% (95% CI 1.5 to 3.0) in cohort studies and 3.3% (95% CI 1.5 to 7.1) in health record studies. The known risk associated with sodium valproate exposure was clear across comparisons with a pooled prevalence of 9.8% (95% CI 8.1 to 11.9) from cohort data and 9.7% (95% CI 7.1 to 13.4) from routine health record studies. This was elevated across almost all comparisons to other monotherapy ASMs, with the absolute risk differences ranging from 5% to 9%. Multiple studies found that the MCM risk is dose-dependent. Children exposed to carbamazepine had an increased MCM prevalence in both cohort studies (4.7%, 95% CI 3.7 to 5.9) and routine health record studies (4.0%, 95% CI 2.9 to 5.4) which was significantly higher than that for the children born to women without epilepsy for both cohort (RR 2.30, 95% CI 1.47 to 3.59) and routine health record studies (RR 1.14, 95% CI 0.80 to 1.64); with similar significant results in comparison to the children of women with untreated epilepsy for both cohort studies (RR 1.44, 95% CI 1.05 to 1.96) and routine health record studies (RR 1.42, 95% CI 1.10 to 1.83). For phenobarbital exposure, the prevalence was 6.3% (95% CI 4.8 to 8.3) and 8.8% (95% CI 0.0 to 9277.0) from cohort and routine health record data, respectively. This increased risk was significant in comparison to the children of women without epilepsy (RR 3.22, 95% CI 1.84 to 5.65) and those born to women with untreated epilepsy (RR 1.64, 95% CI 0.94 to 2.83) in cohort studies; data from routine health record studies was limited. For phenytoin exposure, the prevalence of MCM was elevated for cohort study data (5.4%, 95% CI 3.6 to 8.1) and routine health record data (6.8%, 95% CI 0.1 to 701.2). The prevalence of MCM was higher for phenytoin-exposed children in comparison to children of women without epilepsy (RR 3.81, 95% CI 1.91 to 7.57) and the children of women with untreated epilepsy (RR 2.01. 95% CI 1.29 to 3.12); there were no data from routine health record studies. Pooled data from cohort studies indicated a significantly increased MCM risk for children exposed to lamotrigine in comparison to children born to women without epilepsy (RR 1.99, 95% CI 1.16 to 3.39); with a risk difference (RD) indicating a 1% increased risk of MCM (RD 0.01. 95% CI 0.00 to 0.03). This was not replicated in the comparison to the children of women with untreated epilepsy (RR 1.04, 95% CI 0.66 to 1.63), which contained the largest group of lamotrigine-exposed children (> 2700). Further, a non-significant difference was also found both in comparison to the children of women without epilepsy (RR 1.19, 95% CI 0.86 to 1.64) and children born to women with untreated epilepsy (RR 1.00, 95% CI 0.79 to 1.28) from routine data studies. For levetiracetam exposure, pooled data provided similar risk ratios to women without epilepsy in cohort (RR 2.20, 95% CI 0.98 to 4.93) and routine health record studies (RR 0.67, 95% CI 0.17 to 2.66). This was supported by the pooled results from both cohort (RR 0.71, 95% CI 0.39 to 1.28) and routine health record studies (RR 0.82, 95% CI 0.39 to 1.71) when comparisons were made to the offspring of women with untreated epilepsy. For topiramate, the prevalence of MCM was 3.9% (95% CI 2.3 to 6.5) from cohort study data and 4.1% (0.0 to 27,050.1) from routine health record studies. Risk ratios were significantly higher for children exposed to topiramate in comparison to the children of women without epilepsy in cohort studies (RR 4.07, 95% CI 1.64 to 10.14) but not in a smaller comparison to the children of women with untreated epilepsy (RR 1.37, 95% CI 0.57 to 3.27); few data are currently available from routine health record studies. Exposure in utero to topiramate was also associated with significantly higher RRs in comparison to other ASMs for oro-facial clefts. Data for all other ASMs were extremely limited. Given the observational designs, all studies were at high risk of certain biases, but the biases observed across primary data collection studies and secondary use of routine health records were different and were, in part, complementary. Biases were balanced across the ASMs investigated, and it is unlikely that the differential results observed across the ASMs are solely explained by these biases.
AUTHORS' CONCLUSIONS
Exposure in the womb to certain ASMs was associated with an increased risk of certain MCMs which, for many, is dose-dependent.
Topics: Pregnancy; Child; Female; Humans; Male; Prospective Studies; Topiramate; Lamotrigine; Phenytoin; Cohort Studies; Prenatal Exposure Delayed Effects; Epilepsy
PubMed: 37647086
DOI: 10.1002/14651858.CD010224.pub3 -
Journal of Research in Medical Sciences... 2023Febrile convulsion (FC) is the most common and preventable seizure in children. This study aimed to assess the effectiveness of the diazepam and phenobarbital for... (Review)
Review
Comparing the effect of intermittent diazepam and continuous phenobarbital in preventing recurrent febrile seizures among children under 6 years old: A systematic review and meta-analysis.
BACKGROUND
Febrile convulsion (FC) is the most common and preventable seizure in children. This study aimed to assess the effectiveness of the diazepam and phenobarbital for preventing recurrent FC.
MATERIALS AND METHODS
In this systematic review study, literature published in English language were carefully searched in biological databases (Cochrane Library, Medline, Scopus, CINHAL, Psycoinfo, and Proquest) by February 2020.Randomized clinical trials (RCTs) and Quasi randomized trial were included in the review. Two researchers checked the literature independently. The quality of studies was assessed using the JADAD score. The potential risk for publication bias was assessed by Funnel plot and Egger's test. Meta regression test and sensitivity analysis were used to identify the reasons for heterogeneity. Given the results of assessing heterogeneity, the random effect model in RevMan5.1 software was used for meta analysis.
RESULTS
Four out of 17 studies had compared the effect of diazepam and phenobarbital in preventing recurrent FC. The result of the meta analysis showed that the use of diazepam in comparison with phenobarbital reduces the risk of recurrence FC by 34% (risk ratio = 0.66, 95% confidence interval [CI] = [0.36-1.21]), but the relationship was not statistically significant. In assessing the effect of diazepam or phenobarbital versus placebo, the results showed that the use of diazepam and phenobarbital has reduced the risk of recurrent FC by 49% (risk ratio = 0.51, 95% CI = [0.32-0.79]) and 37% (risk ratio = 0.63, 95% CI = [0.42-0.96)]), respectively, and these relationships were statistically significant ( < 0.05). Results of the meta regression test showed that the follow up time can be a reason for the heterogeneity between trials with the comparison of diazepam versus phenobarbital ( = 0.047, = 0.049) and Phenobarbital versus placebo ( = 0.022, = 0.016). According to the results of Funnel plot and Egger's test, there was evidence of publication bias ( = 0.0584 for comparison of diazepam vs. phenobarbital; = 0.0421 for comparison of diazepam vs. placebo; = 0.0402 for comparison of phenobarbital vs. placebo).
CONCLUSION
The results of this meta analysis indicated that preventive anticonvulsants can be useful in preventing recurrent convulsions in cases of febrile seizures.
PubMed: 37213451
DOI: 10.4103/jrms.jrms_1114_21 -
The Cochrane Database of Systematic... Mar 2023Intraventricular haemorrhage (IVH) is a major complication of preterm birth. Large haemorrhages are associated with a high risk of disability and hydrocephalus.... (Review)
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 in the newborn flow are postulated as causative factors. Another mechanism may involve reperfusion damage from oxygen free radicals. It has been suggested that phenobarbital stabilises blood pressure and may protect against free radicals. This is an update of a review first published in 2001 and updated in 2007 and 2013.
OBJECTIVES
To assess the benefits and harms of the postnatal administration of phenobarbital in preterm infants at risk of developing IVH compared to control (i.e. no intervention or placebo).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL and clinical trial registries in January 2022. A new, more sensitive search strategy was developed, and searches were conducted without date limits. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs in which phenobarbital was given within the first 24 hours of life to preterm infants identified as being at risk of IVH because of gestational age below 34 weeks, birth weight below 1500 g or respiratory failure. Phenobarbital was compared to no intervention or placebo. We excluded infants with serious congenital malformations.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were all grades of IVH and severe IVH (i.e. grade III and IV); secondary outcomes were ventricular dilation or hydrocephalus, hypotension, pneumothorax, hypercapnia, acidosis, mechanical ventilation, neurodevelopmental impairment and death. We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We included 10 RCTs (792 infants). The evidence suggests that phenobarbital results in little to no difference in the incidence of IVH of any grade compared with control (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.84 to 1.19; risk difference (RD) 0.00, 95% CI -0.06 to 0.07; I² for RD = 65%; 10 RCTs, 792 participants; low certainty evidence) and in severe IVH (RR 0.88, 95% CI 0.64 to 1.21; 10 RCTs, 792 participants; low certainty evidence). The evidence is very uncertain about the effect of phenobarbital on posthaemorrhagic ventricular dilation or hydrocephalus (RR 0.62, 95% CI 0.31 to 1.26; 4 RCTs, 271 participants; very low certainty evidence), mild neurodevelopmental impairment (RR 0.57, 95% CI 0.15 to 2.17; 1RCT, 101 participants; very low certainty evidence), and severe neurodevelopmental impairment (RR 1.12, 95% CI 0.44 to 2.82; 2 RCTs, 153 participants; very low certainty evidence). Phenobarbital may result in little to no difference in death before discharge (RR 0.88, 95% CI 0.64 to 1.21; 9 RCTs, 740 participants; low certainty evidence) and mortality during study period (RR 0.98, 95% CI 0.72 to 1.33; 10 RCTs, 792 participants; low certainty evidence) compared with control. We identified no ongoing trials.
AUTHORS' CONCLUSIONS
The evidence suggests that phenobarbital results in little to no difference in the incidence of IVH (any grade or severe) compared with control (i.e. no intervention or placebo). The evidence is very uncertain about the effects of phenobarbital on ventricular dilation or hydrocephalus and on neurodevelopmental impairment. The evidence suggests that phenobarbital results in little to no difference in death before discharge and all deaths during the study period compared with control. Since 1993, no randomised studies have been published on phenobarbital for the prevention of IVH in preterm infants, and no trials are ongoing. The effects of postnatal phenobarbital might be assessed in infants with both neonatal seizures and IVH, in both randomised and observational studies. The assessment of benefits and harms should include long-term outcomes.
Topics: Infant, Newborn; Female; Humans; Infant; Infant, Premature; Phenobarbital; Cerebral Hemorrhage; Infant, Premature, Diseases; Hydrocephalus; Infant, Very Low Birth Weight
PubMed: 36924438
DOI: 10.1002/14651858.CD001691.pub4 -
Progress in Neuro-psychopharmacology &... Jun 2023Data on the ability of anticonvulsants and lithium to enter fetal and newborn circulation has become increasingly available; here we estimated penetration ratios in a...
OBJECTIVE
Data on the ability of anticonvulsants and lithium to enter fetal and newborn circulation has become increasingly available; here we estimated penetration ratios in a series of matrices from combined samples of pregnant/breastfeeding women treated with anticonvulsants or lithium.
METHODS
We conducted a systematic literature search in PubMed/EMBASE for studies with concentrations of anticonvulsants/lithium from maternal blood, amniotic fluid, umbilical cord blood and/or breast milk. Penetration ratios were calculated by dividing the concentrations in amniotic fluid, umbilical cord plasma or breast milk by the maternal concentrations. When data from multiple studies were available, we calculated combined penetration ratios, weighting studies' mean by study size.
RESULTS
Ninety-one eligible studies for brivaracetam, carbamazepine, clonazepam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, lithium, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, topiramate, valproate, vigabatrin and zonisamide were identified. For amniotic fluid, the highest penetration ratios were estimated for levetiracetam (mean 3.56, range 1.27-5.85, n = 2) and lowest for valproate (mean 0.11, range 0.02-1.02, n = 57). For umbilical cord plasma, oxcarbazepine had the highest ratio (mean 1.59, range 0.11-4.33, n = 12) with clonazepam having the lowest (mean 0.55, range 0.52-0.59, n = 2). For breast milk, the highest ratios were observed for oxcarbazepine (mean 3.75, range 0.5-7.0, n = 2), whereas the lowest were observed for valproate (mean 0.04, range 0.01-0.22, n = 121).
DISCUSSION
We observed substantial variability between anticonvulsants and lithium regarding their ability to enter fetal/newborn circulation. Assessing concentrations of anticonvulsants and lithium in maternal samples can provide a surrogate of fetal/infant exposure, although patterns of concentration-dependent effects for maternal/neonatal safety are lacking.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Amniotic Fluid; Anticonvulsants; Fetal Blood; Lithium; Maternal-Fetal Exchange; Milk, Human
PubMed: 36805301
DOI: 10.1016/j.pnpbp.2023.110733 -
Cureus Jan 2023Alcohol withdrawal syndrome (AWS) is a complication frequently encountered among patients who are chronic alcohol abusers. It is considered to have a significant... (Review)
Review
Alcohol withdrawal syndrome (AWS) is a complication frequently encountered among patients who are chronic alcohol abusers. It is considered to have a significant impact on the United States healthcare system. It not only has a toll on the healthcare spending but also contributes to significant morbidity and mortality. Benzodiazepines are considered first line in the treatment of AWS. Since patients with alcohol use disorder have downregulated gamma aminobutyric acid (GABA) receptors, this often leads to benzodiazepine resistance. Phenobarbital is also used in the management of alcohol withdrawal syndrome. Here we present a systematic review and meta-analysis of the efficacy and safety of the drug. We conducted an electronic database search for relevant studies published between the inception of the project and November 20, 2022, in three databases, including Medline/PubMed, Embase, and Cochrane Library. Our study included all original studies with prime focus on the baseline characteristics of patients admitted to the intensive care unit (ICU) for alcohol withdrawal syndrome and management/monitoring protocol implemented for its treatment. The primary outcomes that were the focus of our study consisted of changes in the length of hospital stay, length of ICU stay, and changes in scoring systems (for alcohol withdrawal assessment and monitoring) following the implementation of phenobarbital. The secondary outcomes included complications such as intubation and mortality. Based on our analysis, the mean difference in hospital stay was statistically significant at -2.6 (95% CI, -4.48, -0.72, P=0.007) for phenobarbital compared to the benzodiazepine group. We were unable to comment on the heterogeneity in our meta-analysis due to the standard deviation not being reported in one study. There was no statistically significant difference regarding the length of stay in the intensive care unit compared to the control/comparative arm, with a mean difference of -1.17 (95% CI, -1.17, 0.09, P=0.07), with considerable heterogeneity (I=77%, P=0.002). Our meta-analysis also investigated the risk of intubation between the phenobarbital and the control/comparative group. There was statistically significant difference in the incidence of intubation, relative risk (RR) 0.52 (95% CI, 0.25, 1.08, P=0.08), with considerable heterogeneity (I=80%, P=0.0001). Our study concludes that phenobarbital is an effective tool in the management of AWS in an ICU setting. However, various studies have reported contradictory results, and vital information appears to be lacking. Moreover, there is a lack of uniformity in terms of phenobarbital dosing. Drug administration should be adapted according to the severity of the symptoms. Further studies need to be conducted discussing the safety profile and adverse effects of the drug when it comes to the management of alcohol withdrawal syndrome.
PubMed: 36788902
DOI: 10.7759/cureus.33695 -
Acta Bio-medica : Atenei Parmensis Dec 2022Neonatal stroke is the second cause of acute symptomatic neonatal seizures after hypoxic-ischemic encephalopathy. The aim of this systematic review is to determine which...
BACKGROUND AND AIM
Neonatal stroke is the second cause of acute symptomatic neonatal seizures after hypoxic-ischemic encephalopathy. The aim of this systematic review is to determine which drug among those available represents the best therapeutic choice for treatment of secondary seizures due to neonatal stroke.
METHODS
We performed a systematic review searching on PubMed the keywords "Neonatal", "Stroke", "Seizures" and "Treatment". Search was limited only to English language with no time limit. Last literature search was done on May 30, 2022.
RESULTS
We selected 5 articles involving a total of 52 full-term neonates. In 96.1% the first line treatment was phenobarbital and in 3.9% was used phenobarbital associated with midazolam from the seizure onset but in all of these cases it was necessary to introduce further medications for controlling the seizures. As second line treatment was used lidocaine (response rate of 53.3%), midazolam (response rate of 15.38%) bumetanide (response rate of 100%), and fosphenytoin (no response). As third line treatment was used lidocaine (response rate of 87.5%), Midazolam (response rate of 60%), levetiracetam and clonazepam (response rate of 100%).
CONCLUSIONS
Our review shows that the use of ASMs that act throughout a gabaergic mechanism are inadequate in controlling seizures secondary to neonatal stroke in full-term newborns. Very effective seems to be lidocaine and levetiracetam with an apparent safer profile in short and long term. Bumetanide shows promising results, but they need to be confirmed by phase 3 studies.
Topics: Infant, Newborn; Humans; Levetiracetam; Anticonvulsants; Bumetanide; Midazolam; Phenobarbital; Epilepsy; Lidocaine; Stroke; Infant, Newborn, Diseases
PubMed: 36533757
DOI: 10.23750/abm.v93i6.13440 -
Paediatric Drugs Jan 2023Newborn infants undergoing therapeutic hypothermia (TH) are exposed to multiple painful and stressful procedures. The aim of this systematic review was to assess...
BACKGROUND
Newborn infants undergoing therapeutic hypothermia (TH) are exposed to multiple painful and stressful procedures. The aim of this systematic review was to assess benefits and harms of pharmacological and non-pharmacological interventions for the management of pain and sedation in newborn infants undergoing TH for hypoxic-ischemic encephalopathy.
METHODS
We included randomized and observational studies reporting any intervention (either drugs or non-pharmacological interventions) to manage pain and sedation in newborn infants (> 33 weeks' gestational age) undergoing TH. We included any dose, duration and route of administration. We also included any type and duration of non-pharmacological interventions. Our prespecified primary outcomes were analgesia and sedation assessed using validated pain scales in the neonatal population; circulatory instability; mortality to discharge; and neurodevelopmental disability. A systematic literature search was conducted in the PubMed, Embase, CINAHL, Cochrane CENTRAL, Scopus, and Web of Science databases, with no language restrictions. Included studies underwent risk-of-bias assessment (Cochrane risk-of-bias tool and ROBINS-I) and data extraction performed by two authors independently. The plan had been to use effect measures such as mean difference for continuous outcomes and risk ratio for dichotomous outcomes, however the included studies are presented in a narrative synthesis due to their paucity and heterogeneity.
RESULTS
Ten studies involving 3551 infants were included-one trial and nine observational studies. Most studies examined the use of phenobarbital or other antiepileptic drugs with primary outcomes related to seizure activity. The single trial that was included compared pentoxifylline with placebo. Among the primary outcomes, six studies reported circulatory instability and five reported mortality to discharge without relevant differences; two studies reported on neurodevelopmental disability and one study reported on pain scale. Three studies were ongoing.
CONCLUSIONS
We found limited evidence to establish the benefits and harms of the interventions for the management of pain and sedation in newborn infants undergoing TH. Long-term outcomes were not reported. Given the very low certainty of evidence-due to imprecision of the estimates, inconsistency and limitations in study design (all nine observational studies with overall serious risk of bias)-for all outcomes, clinical trials are required to determine the most effective interventions in this population.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration number: CRD42020205755.
Topics: Humans; Infant, Newborn; Anesthesia; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Observational Studies as Topic; Pain; Pain Management; Randomized Controlled Trials as Topic
PubMed: 36481984
DOI: 10.1007/s40272-022-00546-7 -
Seizure Nov 2022Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available evidence and provide estimates of comparative effectiveness and ranking of treatment effects.
METHODS
All randomized controlled trials studying patients (>1 month of age) with benzodiazepine-resistant SE were included. Outcomes including seizure cessation within 60 min, seizure freedom for 24 h, death, respiratory depression warranting intubation and cardiovascular instability were studied. Conventional and network meta-analyses (NMA) were done.
RESULTS
Seventeen studies were included (16 in NMA). Phenobarbital and high-dose levetiracetam were significantly superior to phenytoin with respect to seizure cessation within 60 min. Network ranking demonstrated that phenobarbital had the highest probability of being the best among the studied interventions followed by high-dose levetiracetam and high-dose valproate. Network meta-analysis was limited by predominant indirect evidence and high heterogeneity.On pairwise comparisons, phenobarbital was found to be associated with a higher risk of need for intubation and cardiovascular instability. Levetiracetam had a better safety profile than fosphenytoin.
CONCLUSIONS
Based on low quality evidence, phenobarbital appears to be the most effective agent for seizure cessation within 60 min of administration in patients with benzodiazepine resistant status epilepticus. High-dose levetiracetam, high-dose valproate and fosphenytoin are probably equally effective. Choice of medication may be guided by effectiveness, safety concerns, availability, cost and systemic co-morbidities.
Topics: Adult; Child; Humans; Anticonvulsants; Benzodiazepines; Levetiracetam; Network Meta-Analysis; Phenobarbital; Phenytoin; Seizures; Status Epilepticus; Valproic Acid; Drug Resistance; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36209676
DOI: 10.1016/j.seizure.2022.09.017 -
Epileptic Disorders : International... Dec 2022We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants,...
We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants, and the wellbeing of infants breastfed by mothers on ASM treatment. Information was extracted from 85 relevant articles. No data on ASM levels in breastmilk or in breastfed infants was identified for cannabidiol, cenobamate, clobazam, eslicarbazepine-acetate, everolimus, felbamate, fenfluramine, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin. For ASMs, with available information on levels in breastfed infants, very low concentrations (in the order of 10% or less of maternal serum concentrations) were reported for carbamazepine, gabapentin, levetiracetam, oxcarbazepine, phenytoin, valproate, and clonazepam. Slightly higher levels (up to approximately 30% of maternal serum concentrations) have been observed with lamotrigine and topiramate, and in single case reports for brivaracetam, lacosamide, and perampanel. High infant levels (30% up to 100% of maternal serum concentrations) have been reported with ethosuximide, phenobarbital and zonisamide. Adverse infant effects during breastfeeding by mothers on ASMs appear to be rare regardless of the type of ASM, but systematic study is limited. Prospective long-term follow-up studies of developmental outcomes among children who have been breastfed by mothers taking ASMs are sparse and have mainly involved children whose mothers were taking carbamazepine, lamotrigine, levetiracetam, phenytoin or valproate as monotherapy while breastfeeding. Although these studies have not indicated poorer outcome among breastfed children compared with those who were not breastfed, further data on long-term outcomes are needed to draw firm conclusions. It is concluded that breastfeeding should in general be encouraged in women taking ASMs, given the well-established benefits of breastfeeding with regard to both short- and long-term infant health in the general population. Counselling needs to be individualized including information on the current knowledge regarding the woman's specific ASM treatment.
Topics: Breast Feeding; Cannabidiol; Carbamazepine; Child; Clobazam; Clonazepam; Epilepsy; Ethosuximide; Everolimus; Felbamate; Female; Fenfluramine; Gabapentin; Humans; Infant; Lacosamide; Lamotrigine; Levetiracetam; Oxcarbazepine; Phenobarbital; Phenytoin; Prospective Studies; Tiagabine; Topiramate; Valproic Acid; Vigabatrin; Zonisamide
PubMed: 36193017
DOI: 10.1684/epd.2022.1492 -
Frontiers in Pharmacology 2022To explore the effectiveness of different anti-seizure medications in preventing early and late post-traumatic epilepsy (PTE). The efficacy, treatment-related...
To explore the effectiveness of different anti-seizure medications in preventing early and late post-traumatic epilepsy (PTE). The efficacy, treatment-related side-effects, and mortality of the different treatments were compared using a ranking model to identify the optimal treatment. A comprehensive literature search was performed using Pubmed, Medline, Embase, and Cochrane library databases. All relevant published articles up to 10 March 2022 were evaluated. The quality of the extracted data was assessed using either the Cochrane risk of bias tool or the Newcastle-Ottawa scale. The primary outcome measures were early or late post-traumatic seizures. The secondary outcome measures were mortality, treatment-related adverse effects, length of hospital stay, and length of stay within the intensive care unit (ICU). A total of seven randomized controlled trials and 18 non-randomized controlled trials were included in this network meta-analysis. The trials included six interventions: Phenytoin (PHT)+phenobarbital (PB), levetiracetam (LEV), PHT, PHT-LEV, lacosamide (LCM), and valproate (VPA). All interventions except VPA significantly reduced the rate of early PTE in TBI patients compared with the placebo. Seven studies reported the impact of four treatments (PHT + PB, LEV, PHT, VPA) on late seizures and showed a significant reduction in the incidence of late seizures in patients with TBI compared with placebo. The impact of PHT, LEV, and VPA on mortality was reported in nine studies. PHT had no impact on mortality, but patients treated with both LEV and VPA had higher mortality than those treated with placebo. The treatment-related adverse effects of LEV, PHT, and LCM were reported in five studies. LEV and PHT had higher treatment-related adverse effects incidence than placebo, while LCM had no effect on treatment related-adverse effects. LEV and PHT prevented early and late PTE. PHT also reduced the mortality rate in patients with TBI. Both LEV and PHT had higher treatment-related adverse effects compared with placebo. However, LEV had a slightly lower incidence of treatment-related adverse effects when compared with PHT. Compared with PHT, LEV did not reduce the length of hospital stay but shortened the length of ICU stays. Therefore, based on the findings of this meta-analysis, we speculate that LEV is the best treatment option for TBI patients. However, further high-quality randomized controlled trials are required to confirm these findings.
PubMed: 36188582
DOI: 10.3389/fphar.2022.1001363