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BMC Veterinary Research Mar 2018Understanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease....
BACKGROUND
Understanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease. However, there is a lack of information about the treatment of feline epilepsy and therefore a systematic review was constructed to assess current evidence for the AEDs' efficacy and tolerability in cats. The methods and materials of our former systematic reviews in canine epilepsy were mostly mirrored for the current systematic review in cats. Databases of PubMed, CAB Direct and Google scholar were searched to detect peer-reviewed studies reporting efficacy and/or adverse effects of AEDs in cats. The studies were assessed with regards to their quality of evidence, i.e. study design, study population, diagnostic criteria and overall risk of bias and the outcome measures reported, i.e. prevalence and 95% confidence interval of the successful and affected population in each study and in total.
RESULTS
Forty studies describing clinical outcomes of AEDs' efficacy and safety were included. Only two studies were classified as "blinded randomised controlled trials". The majority of the studies offered high overall risk of bias and described low feline populations with unclear diagnostic criteria and short treatment or follow-up periods. Individual AED assessments of efficacy and safety profile showed that phenobarbital might currently be considered as the first choice AED followed by levetiracetam and imepitoin. Only imepitoin's safety profile was supported by strong level of evidence. Imepitoin's efficacy as well as remaining AEDs' efficacy and safety profile were supported by weak level of evidence.
CONCLUSIONS
This systematic review reflects an evidence-based assessment of the published data on the AEDs' efficacy and safety for feline epilepsy. Currently, phenobarbital is likely to be the first-line for feline epileptic patients followed by levetiracetam and imepitoin. It is essential that clinicians evaluate both AEDs' effectiveness and tolerability before tailoring AED to the individual patient. Further studies in feline epilepsy treatment are by far crucial in order to establish definite guidelines for AEDs' efficacy and safety.
Topics: Animals; Anticonvulsants; Cat Diseases; Cats; Epilepsy; Treatment Outcome
PubMed: 29499762
DOI: 10.1186/s12917-018-1386-3 -
Journal of Tropical Pediatrics Jan 2021Phenobarbitone is used as a first-line drug for neonatal seizures. However, its poor short- and long-term safety profile is concerning. We aim to systematically... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Phenobarbitone is used as a first-line drug for neonatal seizures. However, its poor short- and long-term safety profile is concerning. We aim to systematically synthesize the data on the efficacy and safety of phenobarbitone as a first-line agent and compare it against other anti-epileptic drugs (AEDs) in neonates.
METHODS
Using keywords related to the study population (neonatal seizure) and intervention (phenobarbitone), we searched CENTRAL, Embase, PubMed and Web of Science until 15 December 2020. Randomized controlled trials (RCTs) comparing phenobarbitone with any other AED as first-line therapy for seizure control in the neonates were considered eligible. The random-effect meta-analysis was done using RevMan 5.3 software.
RESULTS
We screened through 443 records and identified nine eligible studies (719 participants). Five RCTs comparing phenobarbitone with levetiracetam did not find any difference in seizure control with the first dose [risk ratio (RR) 1.43, 95% CI 0.79-2.57] or adverse effects (RR 4.66; 95% CI 0.33-65.83). Two trials comparing phenobarbitone and phenytoin also did not find any difference in seizure control with the first dose (RR 2.09; 95% CI 0.31-14.03) and other outcomes. Only one RCT compared phenobarbitone and lorazepam and found lorazepam to be more efficacious in seizure control with the first dose (RR 0.71; 95% CI 0.53-0.94). Three trials compared neurodevelopmental outcomes, in which levetiracetam was better in two, whereas one did not find any difference.
CONCLUSION
Phenobarbitone is at least as efficacious and safe as other drugs like phenytoin and levetiracetam. The data over the long-term neurodevelopmental outcome are lacking. The existing evidence is insufficient to recommend other drugs over phenobarbitone.
Topics: Anticonvulsants; Carbamazepine; Humans; Infant, Newborn; Phenobarbital; Phenytoin; Seizures
PubMed: 33598701
DOI: 10.1093/tropej/fmab008 -
The Cochrane Database of Systematic... Dec 2018Any type of seizure can be observed in Alzheimer's disease (AD). Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with AD. There...
BACKGROUND
Any type of seizure can be observed in Alzheimer's disease (AD). Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with AD. There are pharmacological and non-pharmacological treatments for epilepsy in people with AD. There are no current systematic reviews to evaluate the efficacy and tolerability of these treatments; this review aims to review those different modalities. This is an updated version of the original Cochrane Review published in Issue 11, 2016.
OBJECTIVES
To assess the efficacy and tolerability of pharmacological or non-pharmacological interventions for the treatment of epilepsy in people with AD (including sporadic AD and dominantly inherited AD).
SEARCH METHODS
For the latest update, on 10 July 2018 we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid 1946- ), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted authors and pharmaceutical companies.
SELECTION CRITERIA
We included randomized and quasi-randomized controlled trials investigating treatment for epilepsy in people with AD, with the outcomes of proportion of participants with seizure freedom or proportion of participants experiencing adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data.
MAIN RESULTS
We included one randomized controlled trial on pharmacological interventions with 95 participants. No studies were found for non-pharmacological interventions. Concerning the proportion of participants with seizure freedom, no significant differences were found for the comparisons of levetiracetam (LEV) versus lamotrigine (LTG) (risk ratio (RR) 1.20, 95% confidence interval (CI) 0.53 to 2.71), LEV versus phenobarbital (PB) (RR 1.01, 95% CI 0.47 to 2.19), or LTG versus PB (RR 0.84, 95% CI 0.35 to 2.02). It seemed that LEV could improve cognition and LTG could relieve depression, while PB and LTG could worsen cognition, and LEV and PB could worsen mood. Unclear risk of bias was found in allocation, blinding and selective reporting. We judged the quality of the evidence to be very low.
AUTHORS' CONCLUSIONS
This review does not provide sufficient evidence to support LEV, PB or LTG for the treatment of epilepsy in people with AD. Regarding efficacy and tolerability, no significant differences were found between LEV, PB and LTG. Large randomized controlled trials with a double-blind, parallel-group design are required to determine the efficacy and tolerability of treatment for epilepsy in people with AD.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Anticonvulsants; Cognition; Depression; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Phenobarbital; Secondary Prevention
PubMed: 30570742
DOI: 10.1002/14651858.CD011922.pub3 -
Acta Paediatrica (Oslo, Norway : 1992) Feb 2015There is a lack of scientific evidence to support the best management of neonatal seizures. Current strategies for neonatal seizure management were investigated by... (Review)
Review
UNLABELLED
There is a lack of scientific evidence to support the best management of neonatal seizures. Current strategies for neonatal seizure management were investigated by analysis of all surveys published during the time period 2000-2012. Methods for seizure diagnosis and availability of electroencephalogram (EEG), including monitoring, varied. Phenobarbital was the drug of first choice, and the use of off-label drugs and treatment times varied.
CONCLUSION
We conclude that there is an urgent need for more evidence-based studies to guide neonatal seizure management.
Topics: Anticonvulsants; Electroencephalography; Humans; Infant, Newborn; Phenobarbital; Seizures
PubMed: 25251733
DOI: 10.1111/apa.12812 -
Journal of Clinical Pharmacy and... Apr 2017Voriconazole is a triazole antifungal agent and is extensively metabolized via cytochrome P450 (CYP450); therefore, special precautions need to be taken when... (Review)
Review
WHAT IS KNOWN AND OBJECTIVES
Voriconazole is a triazole antifungal agent and is extensively metabolized via cytochrome P450 (CYP450); therefore, special precautions need to be taken when co-administered with a known CYP450 inducer, which may lead to treatment failure. The influence of some CYP450 inducers on the pharmacokinetics of voriconazole has been described in previous studies, but a systematic review was lacking. In this study, we carried out a systematic review to assess the influence of CYP450 inducers on the pharmacokinetic (PK) parameters of voriconazole.
METHODS
Pubmed, Embase, Cochrane Library, Clinicaltrials.gov and three Chinese databases (CNKI, CBM and WanFang) were searched through January 2016. Interventional and observational studies comparing the PK parameters of voriconazole used alone or with CYP450 inducers in healthy volunteers and patients were included. The outcomes included were the area under the plasma concentration-time curve (AUC), peak plasma concentrations (C ) and trough plasma concentrations (C ). The quality of the included studies was assessed using Cochrane's risk of bias tool, Newcastle-Ottawa Scale (NOS) and a modified risk of bias tool for pharmacokinetic before-and-after studies.
RESULTS AND DISCUSSION
Sixteen studies were included in this review: three randomized controlled trials (RCTs), five single-arm before-after studies (SBAs), six cohort studies and two case reports. All studies except case reports had moderate to high quality. Of the 11 inducers reviewed, efavirenz, ritonavir (chronic use), phenytoin, rifampin and rifabutin significantly decreased mean AUC and C of voriconazole; St John's wort significantly decreased only mean AUC; rifampin, rifabutin, phenobarbital and carbamazepine significantly decreased mean C . Etravirine and Ginkgo biloba did not reveal any such influence. The influence of glucocorticoids may depend on its type and dose.
WHAT IS NEW AND CONCLUSIONS
To conclude, the combination use of high-dose efavirenz, high-dose ritonavir, St John's wort, rifampin, phenobarbital, or carbamazepine with voriconazole is contraindicated as instructed in the drug label. Low-dose efavirenz, low-dose ritonavir, rifabutin and phenytoin may be used together with voriconazole provided TDM and dose adjustment of voriconazole. Moreover, this study shows there is low risk of drug-drug interactions when voriconazole is co-administered with etravirine or G. biloba; however, whether the use of glucocorticoids has a clinically significant effect on voriconazole still requires more evidence. This study also highlights the lack of clinical studies and future high-quality studies assessing the influence of CYP450 inducers on voriconazole. PK parameters and dosing optimization should be designed to provide a more definitive answer regarding the necessity of TDM and the recommendations for dose adjustment of voriconazole.
Topics: Antifungal Agents; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme Inducers; Drug Interactions; Humans; Voriconazole
PubMed: 28177134
DOI: 10.1111/jcpt.12493 -
JAMA Pediatrics Mar 2019Incidence of neonatal abstinence syndrome is rising rapidly, and optimal pharmacotherapy may meaningfully reduce length of treatment.
IMPORTANCE
Incidence of neonatal abstinence syndrome is rising rapidly, and optimal pharmacotherapy may meaningfully reduce length of treatment.
OBJECTIVE
To compare pharmacological therapies for neonatal abstinence syndrome.
DATA SOURCES
Systematic review and network meta-analysis of Medline (1946-June 2018), Embase (1974-June 2018), Cochrane CENTRAL (1966-June 2018), Web of Science (1900-June 2018), and ClinicalTrials.gov (June 2018).
STUDY SELECTION
Randomized clinical trials of pharmacological treatments for neonatal abstinence syndrome alone or in combination with adjuvant treatments. Abstract, title, and full-text screening were conducted independently by 2 reviewers (T.D. and C.G.).
DATA EXTRACTION AND SYNTHESIS
Data extraction was conducted independently by 2 reviewers (T.D. and C.G.) according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-Network Meta-Analyses guidelines. Quality was assessed with the Cochrane Risk of Bias tool and data were pooled with fixed-effect models as a result of the low number of trials that were included in the analysis.
MAIN OUTCOMES AND MEASURES
The primary outcome was the length of treatment. The length of stay, need for adjuvant therapy, and adverse events were considered as secondary outcomes.
RESULTS
Eighteen trials (N = 1072) were eligible for inclusion. The treatments that were included in the length of treatment analysis were buprenorphine, clonidine, diluted tincture of opium and clonidine, diluted tincture of opium, morphine, methadone, and phenobarbital. Sublingual buprenorphine was considered the optimal treatment for a reduction in the length of treatment (days: mean difference vs morphine, -12.75 [95% CI, -17.97 to -7.58]; median rank, 1 [3-1]) and length of stay (days: mean difference vs morphine, -11.43 [95% CI, -16.95 to -5.82]; median rank, 1 [3-1]) but not the need for adjuvant treatment (odds ratio vs morphine, 1.23 [95% CI, 0.46-3.44]; median rank, 3 [5-1]). The results were robust to bias but sensitive to imprecision.
CONCLUSIONS AND RELEVANCE
The current evidence suggests that buprenorphine is the optimal treatment for neonatal abstinence treatment, but limitations are considerable and wide-scale adoption requires a large multisite trial. Morphine, which is considered standard of care in most hospitals, was the lowest-ranked opioid for length of treatment and length of stay.
Topics: Analgesics, Opioid; Buprenorphine; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Network Meta-Analysis; Treatment Outcome
PubMed: 30667476
DOI: 10.1001/jamapediatrics.2018.5044 -
Developmental Medicine and Child... Mar 2024To review the evidence of the effects of neonatal magnesium sulphate for neuroprotection in perinatal asphyxia and hypoxic-ischaemic encephalopathy (HIE). (Review)
Review
AIM
To review the evidence of the effects of neonatal magnesium sulphate for neuroprotection in perinatal asphyxia and hypoxic-ischaemic encephalopathy (HIE).
METHOD
This was a systematic review of randomized controlled trials (RCTs) (with meta-analysis) and non-RCTs assessing magnesium sulphate for treating perinatal asphyxia and HIE at 35 weeks or more gestation (primary outcomes: neonatal death and death or long-term major neurodevelopmental disability).
RESULTS
Twenty-five RCTs (2099 infants) and four non-RCTs (871 infants) were included, 23 in low- and middle-income countries (LMICs). In RCTs, reductions in neonatal death with magnesium sulphate versus placebo or no treatment (risk ratio [RR] = 0.68; 95% confidence interval [CI] = 0.53-0.86; 13 RCTs), and magnesium sulphate with melatonin versus melatonin alone (RR = 0.74; 95% CI = 0.58-0.95; one RCT) were observed. No difference in neonatal death was seen for magnesium sulphate with therapeutic hypothermia versus therapeutic hypothermia alone (RR = 0.66, 95% CI = 0.34-1.26; three RCTs), or magnesium sulphate versus phenobarbital (RR = 3.00; 95% CI = 0.86-10.46; one RCT). No reduction in death or long-term neurodevelopmental disability (RR = 0.52; 95% CI = 0.14-1.89; one RCT) but reductions in several short-term adverse outcomes were observed with magnesium sulphate. Evidence was low- to very-low certainty because of risk of bias and imprecision.
INTERPRETATION
Given the uncertainty of the current evidence, further robust neonatal magnesium sulphate research is justified. This may include high-quality studies to determine stand-alone effects in LMICs and effects with and after therapeutic hypothermia in high-income countries.
PubMed: 38468452
DOI: 10.1111/dmcn.15899 -
CNS & Neurological Disorders Drug... 2021While phenobarbital (PB) is commonly used for the management of seizures in newborns and pediatrics, its administration may accompany acute poisoning. We aimed to review...
OBJECTIVES
While phenobarbital (PB) is commonly used for the management of seizures in newborns and pediatrics, its administration may accompany acute poisoning. We aimed to review the literature to find out the frequency of PB poisonings in newborns and children with seizures.
METHOD
A literature search was performed by two independent reviewers to find relevant articles about PB toxicity in neonates and pediatrics that were treated for the seizure.
RESULTS
18 articles met the inclusion criteria and were included in this systematic review. The main reasons for PB poisoning in studied patients were therapeutic intoxication. Reported signs of PB poisoning were lethargy, sedation, lack of sucking, fever, skin rash, hepatic inflammation and alopecia. Moreover, respiratory depression, encephalopathy, myocardial failure, syndrome of inappropriate antidiuretic hormone, and coma were among the complications of acute PB toxicity in children and infants.
CONCLUSION
PB therapy for the management of seizures in newborns and children might be associated with poisoning. Although supportive and symptomatic treatments are available for PB overdose, it should be administered with caution, using drug monitoring to avoid toxicity.
Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy, Generalized; Humans; Infant; Infant, Newborn; Phenobarbital; Seizures
PubMed: 33290203
DOI: 10.2174/1871527319666201207205916 -
Seizure May 2022Recent position papers and guidelines encourage women with epilepsy (WWE) to exclusively breastfeed their infants because the benefits to their infants outweigh the... (Review)
Review
BACKGROUND
Recent position papers and guidelines encourage women with epilepsy (WWE) to exclusively breastfeed their infants because the benefits to their infants outweigh the potential adverse effects caused by exposure to antiseizure medications (ASMs).
OBJECTIVE
The objectives of this review were: to evaluate concentrations of ASMs in breastmilk of lactating WWE, qualitatively synthesize evidence that can be used to estimate theoretical doses as estimated daily intake (EDI) and relative infant dose (RID) of ASMs, and to evaluate potential risks to infants as a result of exposure to ASMs from breastmilk.
METHODS
This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42020223645. The databases: MEDLINE/PubMed, EMBASE, CINAHL/EBSCO, COCHRANE, SpringerLink, ScienceDirect, Summon, WHO International Clinical Trials Registry Platform, and SCOPUS were systematically searched. A qualitative synthesis was adopted in this study.
RESULTS
A total of 15 records were included in this systematic review. The included studies reported levels of 8 ASMs in the breastmilk of WWE. The highest RIDs of carbamazepine, lamotrigine, primidone, phenobarbital, gabapentin, valproic acid, ethosuximide, levetiracetam, and topiramate were 3.70%, 36.33%, 4.96%, 3.15%, 4.37%, 1.90%, 31.49%, 12.50%, and 12.18%, respectively. Breastfeeding might be limited or even discontinued when signs of excessive sedation/drowsiness and/or poor weight gain are evident on infants exposed to primidone and phenobarbital, ethosuximide/primidone, or ethosuximide/phenobarbital.
CONCLUSIONS
Concentrations of ASMs can be detected in breastmilk of WWE and plasma/serum of infants exposed via breastmilk. Healthcare providers and WWE might use the findings of this study to make informed decisions on the safety of breastfeeding while taking ASMs.
Topics: Anticonvulsants; Breast Feeding; Epilepsy; Ethosuximide; Female; Humans; Infant; Lactation; Milk, Human; Phenobarbital; Primidone
PubMed: 35427849
DOI: 10.1016/j.seizure.2022.03.017 -
Journal of Critical Care Apr 2016To perform a systematic review of the clinical trials concerning the use of barbiturates for the treatment of acute alcohol withdrawal syndrome (AWS). (Review)
Review
PURPOSE
To perform a systematic review of the clinical trials concerning the use of barbiturates for the treatment of acute alcohol withdrawal syndrome (AWS).
MATERIALS AND METHODS
A literature search of MEDLINE, EMBASE, and the Cochrane Library, together with a manual citation review was conducted. We selected English-language clinical trials (controlled and observational studies) evaluating the efficacy and safety of barbiturates compared with benzodiazepine (BZD) therapy for the treatment of AWS in the acute care setting. Data extracted from the included trials were duration of delirium, number of seizures, length of intensive care unit and hospital stay, cumulated doses of barbiturates and BZDs, and respiratory or cardiac complications.
RESULTS
Seven studies consisting of 4 prospective controlled and 3 retrospective trials were identified. Results from all the included studies suggest that barbiturates alone or in combination with BZDs are at least as effective as BZDs in the treatment of AWS. Furthermore, barbiturates appear to have acceptable tolerability and safety profiles, which were similar to those of BZDs in patients with AWS.
CONCLUSIONS
Although the evidence is limited, based on our findings, adding phenobarbital to a BZD-based regimen is a reasonable option, particularly in patients with BZD-refractory AWS.
Topics: Alcohol Withdrawal Delirium; Barbiturates; Benzodiazepines; Clinical Protocols; Clinical Trials as Topic; Critical Care; Delirium; Drug Therapy, Combination; Ethanol; Humans; Length of Stay; Prospective Studies; Retrospective Studies; Substance Withdrawal Syndrome
PubMed: 26795441
DOI: 10.1016/j.jcrc.2015.11.022