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The Cochrane Database of Systematic... May 2021Any type of seizure can be observed in Alzheimer's disease. Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with Alzheimer's...
BACKGROUND
Any type of seizure can be observed in Alzheimer's disease. Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with Alzheimer's disease. There are pharmacological and non-pharmacological treatments for epilepsy in people with Alzheimer's disease, however there are no current systematic reviews to evaluate the efficacy and tolerability of these treatments. This review aims to investigate these different modalities. This is an updated version of the Cochrane Review previously published in 2018.
OBJECTIVES
To assess the efficacy and tolerability of pharmacological or non-pharmacological interventions for the treatment of epilepsy in people with Alzheimer's disease (including sporadic Alzheimer's disease and dominantly inherited Alzheimer's disease).
SEARCH METHODS
For the latest update, on 3 August 2020 we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 31 July 2020). CRS Web includes randomized or quasi-randomized controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups, including Cochrane Epilepsy. In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers, reference lists and relevant conference proceedings; we also contacted trial authors and pharmaceutical companies.
SELECTION CRITERIA
We included randomized and quasi-randomized controlled trials investigating treatment for epilepsy in people with Alzheimer's disease, with the primary outcomes of proportion of participants with seizure freedom and 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 there being limited available data.
MAIN RESULTS
We included one randomized controlled trial (RCT) on pharmacological interventions; the trial included 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 versus lamotrigine (RR) 1.20, 95% CI 0.53 to 2.71; 67 participants; very low-certainty evidence), levetiracetam versus phenobarbital (RR 1.01, 95% CI 0.47 to 2.19; 66 participants; very low-certainty evidence), or lamotrigine versus phenobarbital (RR 0.84, 95% CI 0.35 to 2.02; 57 participants; very low-certainty evidence). It seemed that levetiracetam could improve cognition and lamotrigine could relieve depression, while phenobarbital and lamotrigine could worsen cognition, and levetiracetam and phenobarbital could worsen mood. The risk of bias relating to allocation, blinding and selective reporting was unclear. We judged the certainty of the evidence for all outcomes to be very low.
AUTHORS' CONCLUSIONS
This review does not provide sufficient evidence to support levetiracetam, phenobarbital or lamotrigine for the treatment of epilepsy in people with Alzheimer's disease. Regarding efficacy and tolerability, no significant differences were found between levetiracetam, phenobarbital and lamotrigine. Large RCTs with a double-blind, parallel-group design are required to determine the efficacy and tolerability of treatment for epilepsy in people with Alzheimer's disease.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Anticonvulsants; Cognition; Depression; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Phenobarbital; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 33973646
DOI: 10.1002/14651858.CD011922.pub4 -
Italian Journal of Pediatrics Apr 2021The existing treatment options for neonatal seizures have expanded over the last few decades, but no consensus has been reached regarding the optimal therapeutic...
AIM
The existing treatment options for neonatal seizures have expanded over the last few decades, but no consensus has been reached regarding the optimal therapeutic protocols. We systematically reviewed the available literature examining neonatal seizure treatments to clarify which drugs are the most effective for the treatment of specific neurologic disorders in newborns.
METHOD
We reviewed all available, published, literature, identified using PubMed (published between August 1949 and November 2020), that focused on the pharmacological treatment of electroencephalogram (EEG)-confirmed neonatal seizures.
RESULTS
Our search identified 427 articles, of which 67 were included in this review. Current knowledge allowed us to highlight the good clinical and electrographic responses of genetic early-onset epilepsies to sodium channel blockers and the overall good response to levetiracetam, whose administration has also been demonstrated to be safe in both full-term and preterm newborns.
INTERPRETATION
Our work contributes by confirming the limited availability of evidence that can be used to guide the use of anticonvulsants to treat newborns in clinical practice and examining the efficacy and potentially harmful side effects of currently available drugs when used to treat the developing newborn brain; therefore, our work might also serve as a clinical reference for future studies.
Topics: Anticonvulsants; Channelopathies; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Seizures; Sodium Potassium Chloride Symporter Inhibitors; Stroke
PubMed: 33827647
DOI: 10.1186/s13052-021-01027-2 -
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 -
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 -
Thrombosis Research Oct 2020Direct oral anticoagulants (DOACs) have emerged as safe and effective alternatives to Vitamin-K antagonists for treatment and prevention of arterial and venous... (Review)
Review
BACKGROUND
Direct oral anticoagulants (DOACs) have emerged as safe and effective alternatives to Vitamin-K antagonists for treatment and prevention of arterial and venous thrombosis. Due to their novelty, pharmacokinetic DOAC drug-drug interactions (DDIs) that result in clinical adverse events have not been well-documented.
OBJECTIVE
This study aims to systematically review reported pharmacokinetic DDIs resulting in clinical adverse events through documented observational evidence to better inform clinicians in clinical practice.
METHODS
A comprehensive literature review of EMBASE, MEDLINE, and Ovid HealthStar was conducted through March 10th, 2020. Two independent reviewers screened and extracted data from eligible articles according to pre-established inclusion and exclusion criteria. Articles reporting bleeding or thrombotic outcomes in non-controlled (observational) settings resulting from suggested pharmacokinetic DOAC DDIs were included.
RESULTS
A total of 5567 citations were reviewed, of which 24 were included following data extraction. The majority were case reports (n = 21) documenting a single adverse event resulting from a suspected DOAC DDI, while the remaining papers were a case series (n = 1) and cohort studies (n = 2). The most commonly reported interacting drugs were amiodarone and ritonavir (bleeding), and phenobarbital, phenytoin, and carbamazepine (thrombosis). Bleeding events more often resulted from a combined mechanism (P-glycoprotein AND CYP3A4 inhibition), whereas thrombotic events resulted from either combined OR single P-glycoprotein/CYP3A4 induction.
CONCLUSION
Current literature evaluating the real-world risk of DOAC DDIs is limited to few case reports and retrospective observational analyses. Clinicians are encouraged to continue to report suspected drug interactions resulting in adverse events.
Topics: Administration, Oral; Anticoagulants; Drug Interactions; Hemorrhage; Humans; Observational Studies as Topic; Pharmaceutical Preparations; Retrospective Studies
PubMed: 33213849
DOI: 10.1016/j.thromres.2020.08.016 -
The Journal of Maternal-fetal &... Oct 2022Neonatal seizures represent the most frequent presenting sign of any neurological abnormality secondary to various etiologies in the neonatal period. Phenobarbitone (PB)...
BACKGROUND
Neonatal seizures represent the most frequent presenting sign of any neurological abnormality secondary to various etiologies in the neonatal period. Phenobarbitone (PB) has been used as first-line anti-epileptic drug in the treatment of seizures but concerns have been raised regarding its neuro-apoptotic effects over the developing brain. Levetiracetam (LEV) is a newer anti-epileptic drug with neuroprotective property and has been used in adults and pediatric patient but its use in neonates have very limited experience. Recently many neonatal studies have sought the role of LEV in the management of neonatal seizures.
AIMS AND OBJECTIVE
To evaluate the efficacy of Levetiracetam in the management of neonatal seizures.
SEARCH METHODS
The literature search was done for this systematic review by searching the Cochrane Central Register of Controlled Trials (CENTRAL), and other various electronic databases including PubMed and various sites for ongoing trials and abstracts of conferences.
RESULTS
Two eligible studies were analyzed that fulfilled the inclusion criteria of the systematic review. Fifteen studies were excluded due to the non-fulfillment of inclusion criteria. The primary outcome of both studies was to see the efficiency of LEV in controlling neonatal seizures when compared to PB. Better seizure control after a single loading dose of LEV was seen. Rates of seizure cessation at 24 h was also better in the LEV arm. Neonatal seizures secondary to hypoxic-ischemic encephalopathy (HIE) and receiving therapeutic hypothermia were better controlled with LEV. The side effect of LEV was significantly less when compared to PB.
CONCLUSION
Levetiracetam has shown to have promising anti-epileptic properties for the management of neonatal seizure with better efficacy and less or no side effects. There is a need to conduct more randomized controlled trials seeking the role of LEV in the acute management of neonatal seizures and also for assessing its neuroprotective role and neurodevelopmental outcome in these neonates.
Topics: Adult; Anticonvulsants; Child; Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Piracetam; Seizures
PubMed: 33172319
DOI: 10.1080/14767058.2020.1844651 -
Clinical Drug Investigation Jan 2021The optimal choice for first- and second-line antiseizure medications for pediatric patients with convulsive status epilepticus remains ambiguous. The present study... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
The optimal choice for first- and second-line antiseizure medications for pediatric patients with convulsive status epilepticus remains ambiguous. The present study aimed to estimate the comparative effect on the efficacy and safety of different antiseizure medications in pediatric patients with status epilepticus and provide evidence for clinical practice.
METHODS
We searched PubMed, EMBASE, and the Cochrane Library for eligible randomized controlled trials. Inclusion criteria included: (1) pediatric patients; (2) diagnosis of status epilepticus; and (3) randomized controlled trials. Exclusion criteria were: (1) mixed population without a pediatric subgroup analysis; (2) not status epilepticus; (3) received the study drug prior to admission; (4) sample size fewer than 30; and (5) not randomized controlled trials. Primary outcome was seizure cessation. Secondary outcomes were seizure recurrence within 24 h, respiratory depression, and admission to an intensive care unit. The hierarchy of competing antiseizure medications was presented using the surface under the cumulative ranking curve.
RESULTS
Eight first-line antiseizure medication studies involving 1686 participants and eight second-line antiseizure medication studies involving 1711 participants were eligible for analysis. Midazolam, diazepam, lorazepam, and paraldehyde were administered as first-line antiseizure medications. Valproate, phenobarbital, phenytoin, fosphenytoin, and levetiracetam were investigated as second-line antiseizure medications. No significant differences were observed across first- and second-line antiseizure medications. Midazolam ranked the best for primary and secondary outcomes among the first-line antiseizure medications. Phenobarbital ranked the best for seizure cessation and a lower risk of admission to the intensive care unit. Valproate had superiority in preventing recurrence within 24 h. Levetiracetam had the lowest probability of developing respiratory depression.
CONCLUSIONS
This study demonstrated the hierarchy of competing interventions. Midazolam could be a better option for first-line treatment. Phenobarbital, levetiracetam, and valproate had their respective superiority in the second-line intervention. This study may provide useful information for clinical decision making under different circumstances.
Topics: Anticonvulsants; Child; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Seizures; Status Epilepticus
PubMed: 33145680
DOI: 10.1007/s40261-020-00975-7 -
Frontiers in Endocrinology 2020Still circa 25% to 30% of patients with epilepsy cannot be efficiently controlled with available antiepileptic drugs so newer pharmacological treatment options have been...
Still circa 25% to 30% of patients with epilepsy cannot be efficiently controlled with available antiepileptic drugs so newer pharmacological treatment options have been continuously searched for. In this context, a group of endogenous or exogenous neurosteroids allosterically positively modulating GABA-A receptors may offer a promising approach. Among endogenous neurosteroids synthesized in the brain, allopregnanolone or allotetrahydrodeoxycorticosterone have been documented to exert anticonvulsant activity in a number of experimental models of seizures-pentylenetetrazol-, bicuculline- pilocarpine-, or 6 Hz-induced convulsions in rodents. Neurosteroids can also inhibit fully kindled seizures and some of them have been reported to counteract maximal electroshock-induced convulsions. An exogenous neurosteroid, alphaxalone, significantly elevated the threshold for maximal electroconvulsions in mice but it did not potentiate the anticonvulsive action of a number of conventional antiepileptic drugs against maximal electroshock-induced seizures. Androsterone not only elevated the threshold but significantly enhanced the protective action of carbamazepine, gabapentin and phenobarbital against maximal electroshock in mice, as well. Ganaxolone (a 3beta-methylated analog of allopregnanolone) needs special consideration for two reasons. First, it performed better than conventional antiepileptic drugs, diazepam or valproate, in suppressing convulsive and lethal effects of pentylenetetrazol in pentylenetetrazol-kindled mice. Second, ganaxolone has been evaluated in the randomized, double-blind, placebo-controlled phase 2 trial in patients with intractable partial seizures, taking maximally 3 antiepileptic drugs. The initial results indicate that add-on therapy with ganaxolone resulted in reduced seizure frequency with adverse effect being mainly mild to moderate. Possibly, ganaxolone may be also considered against catamenial seizures. Some positive effects of ganaxolone as an adjuvant were also observed in children with refractory seizures and its use may also prove efficient for the management of neonatal seizures associated with hypoxic injury. Neurosteroids positively modulating GABA-A receptor complex exert anticonvulsive activity in many experimental models of seizures. Their interactions with antiepileptic drugs seem ambiguous in mice. Initial clinical data indicate that ganaxolone may provide a better seizure control in patients with drug-resistant epilepsy.
Topics: Allosteric Regulation; Animals; Anticonvulsants; Epilepsy; GABA-A Receptor Agonists; Humans; Neurosteroids; Seizures; Treatment Outcome
PubMed: 33117274
DOI: 10.3389/fendo.2020.541802 -
European Journal of Clinical... Mar 2021Population pharmacokinetics with Bayesian forecasting provides for an effective approach when individualized drug dosing, while phenobarbital is a narrow therapeutic...
AIMS AND BACKGROUND
Population pharmacokinetics with Bayesian forecasting provides for an effective approach when individualized drug dosing, while phenobarbital is a narrow therapeutic index drug that requires therapeutic drug monitoring. To date, several population pharmacokinetic models have been developed for phenobarbital, these showing a number of significant predictors of phenobarbital clearance and volume of distribution. We have therefore conducted a systematic review to summarize how these predictors affect phenobarbital pharmacokinetics as well as their relationships with pharmacokinetic parameters.
METHOD
A systematic search for studies of phenobarbital population pharmacokinetics that were carried out in humans and that employed a nonlinear mixed-effect approaches was made using the PubMed, Scopus, CINAHL Complete, and ScienceDirect databases. The search covered the period from these databases' inception to March 2020.
RESULTS
Eighteen studies were included in this review, all of which used a one-compartment structure. The estimated phenobarbital clearance and volume of distribution ranged from 0.0034 to 0.0104 L/h/kg and 0.37 to 1.21 L/kg, respectively, with body weight, age, and concomitant antiepileptic drugs being the three most frequently identified predictors of clearance. Most models were validated through the use of an advanced internal approach.
CONCLUSION
Phenobarbital clearance may be predicted from previously developed population pharmacokinetic models and their significant covariate-parameter relationships along with Bayesian forecasting. However, when applying these models in a target population, an external evaluation of these models using the target population is warranted, and it is recommended that future research be conducted to investigate the link between population pharmacokinetics and pharmacodynamics.
Topics: Anticonvulsants; Bayes Theorem; Drug Monitoring; Humans; Models, Biological; Nonlinear Dynamics; Phenobarbital; Therapeutic Index; Tissue Distribution
PubMed: 33078242
DOI: 10.1007/s00228-020-03011-x -
Journal of Pain and Symptom Management Apr 2021Near the end of life when patients experience refractory symptoms, palliative sedation may be considered as a last treatment. Clinical guidelines have been developed,... (Review)
Review
CONTEXT
Near the end of life when patients experience refractory symptoms, palliative sedation may be considered as a last treatment. Clinical guidelines have been developed, but they are mainly based on expert opinion or retrospective chart reviews. Therefore, evidence for the clinical aspects of palliative sedation is needed.
OBJECTIVES
To explore clinical aspects of palliative sedation in recent prospective studies.
METHODS
Systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered at PROSPERO. PubMed, CINAHL, Cochrane, MEDLINE, and EMBASE were searched (January 2014-December 2019), combining sedation, palliative care, and prospective. Article quality was assessed.
RESULTS
Ten prospective articles were included, involving predominantly patients with cancer. Most frequently reported refractory symptoms were delirium (41%-83%), pain (25%-65%), and dyspnea (16%-59%). In some articles, psychological and existential distress were mentioned (16%-59%). Only a few articles specified the tools used to assess symptoms. Level of sedation assessment tools were the Richmond Agitation Sedation Scale, Ramsay Sedation Scale, Glasgow Coma Scale, and Bispectral Index monitoring. The palliative sedation practice shows an underlying need for proportionality in relation to symptom intensity. Midazolam was the main sedative used. Other reported medications were phenobarbital, promethazine, and anesthetic medication-propofol. The only study that reported level of patient's discomfort as a palliative sedation outcome showed a decrease in patient discomfort.
CONCLUSION
Assessment of refractory symptoms should include physical evaluation with standardized tools applied and interviews for psychological and existential evaluation by expert clinicians working in teams. Future research needs to evaluate the effectiveness of palliative sedation for refractory symptom relief.
Topics: Hospice and Palliative Care Nursing; Humans; Hypnotics and Sedatives; Palliative Care; Prospective Studies; Retrospective Studies; Terminal Care
PubMed: 32961218
DOI: 10.1016/j.jpainsymman.2020.09.022