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The Cochrane Database of Systematic... Apr 2020This is an updated version of the Cochrane Review previously published in 2018. The incidence of seizures following supratentorial craniotomy for non-traumatic pathology...
BACKGROUND
This is an updated version of the Cochrane Review previously published in 2018. The incidence of seizures following supratentorial craniotomy for non-traumatic pathology has been estimated to be between 15% to 20%; however, the risk of experiencing a seizure appears to vary from 3% to 92% over a five-year period. Postoperative seizures can precipitate the development of epilepsy; seizures are most likely to occur within the first month of cranial surgery. The use of antiepileptic drugs (AEDs) administered pre- or postoperatively to prevent seizures following cranial surgery has been investigated in a number of randomised controlled trials (RCTs).
OBJECTIVES
To determine the efficacy and safety of AEDs when used prophylactically in people undergoing craniotomy and to examine which AEDs are most effective.
SEARCH METHODS
For the latest update we searched the following databases on 29 September 2019: Cochrane Epilepsy Group Specialized Register, CENTRAL, MEDLINE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). We did not apply any language restrictions.
SELECTION CRITERIA
We included RCTs of people with no history of epilepsy who were undergoing craniotomy for either therapeutic or diagnostic reasons. We included trials with adequate randomisation methods and concealment; these could either be blinded or unblinded parallel trials. We did not stipulate a minimum treatment period, and we included trials using active drugs or placebo as a control group.
DATA COLLECTION AND ANALYSIS
Three review authors (JW, JG, YD) independently selected trials for inclusion, extracted data and assessed risk of bias. We resolved any disagreements through discussion. Outcomes investigated included the number of participants experiencing seizures (early (occurring within first week following craniotomy), and late (occurring after first week following craniotomy)), the number of deaths and the number of people experiencing disability and adverse effects. Due to the heterogeneous nature of the trials, we did not combine data from the included trials in a meta-analysis; we presented the findings of the review in narrative format. Visual comparisons of outcomes are presented in forest plots.
MAIN RESULTS
We included 10 RCTs (N = 1815), which were published between 1983 and 2015. Three trials compared a single AED (phenytoin) with placebo or no treatment. One, three-armed trial compared two AEDs (phenytoin, carbamazepine) with no treatment. A second three-armed trial compared phenytoin, phenobarbital with no treatment. Of these five trials comparing AEDs with placebo or no treatment, two trials reported a statistically significant advantage for AED treatment compared to controls for early seizure occurrence; all other comparisons showed no clear or statistically significant differences between AEDs and control treatment. None of the trials that were head-to-head comparisons of AEDs (phenytoin versus sodium valproate, phenytoin versus phenobarbital, levetiracetam versus phenytoin, zonisamide versus phenobarbital) reported any statistically significant differences between treatments for either early or late seizure occurrence. Only five trials reported incidences of death. One trial reported statistically significantly fewer deaths in the carbamazepine and no-treatment groups compared with the phenytoin group after 24 months of treatment, but not after six months of treatment. Incidences of adverse effects of treatment were poorly reported; however, three trials did show that significantly more adverse events occurred on phenytoin compared to valproate, placebo, or no treatment. No trials reported any results relating to functional outcomes such as disability. We considered the evidence to be of low certainty for all reported outcomes due to methodological issues and variability of comparisons made in the trials.
AUTHORS' CONCLUSIONS
There is limited, low-certainly evidence to suggest that AED treatment administered prophylactically is either effective or not effective in the prevention of postcraniotomy (early or late) seizures. The current evidence base is limited due to the different methodologies employed in the trials and inconsistencies in the reporting of outcomes including deaths and adverse events. Further evidence from good-quality, contemporary trials is required in order to assess the clinical effectiveness of prophylactic AED treatment compared to placebo or no treatment, or other AEDs in preventing postcraniotomy seizures in this select group of patients.
Topics: Anticonvulsants; Carbamazepine; Craniotomy; Humans; Isoxazoles; Levetiracetam; Phenobarbital; Phenytoin; Piracetam; Postoperative Complications; Randomized Controlled Trials as Topic; Seizures; Valproic Acid; Zonisamide
PubMed: 32343399
DOI: 10.1002/14651858.CD007286.pub5 -
International Journal of Rheumatic... Apr 2020
Topics: Adult; Anticonvulsants; Antirheumatic Agents; Arthritis, Rheumatoid; Carbamazepine; Complex Regional Pain Syndromes; Diagnostic Errors; Drug Substitution; Drug Tapering; Epilepsy; Female; Humans; Phenobarbital; Predictive Value of Tests; Pregabalin; Treatment Outcome; Unnecessary Procedures
PubMed: 32100469
DOI: 10.1111/1756-185X.13813 -
The International Journal of... Jan 2021Status epilepticus (SE) is a common neurologic emergency. The present study constitutes a meta-analysis of published randomized control trials (RCTs) evaluating the use... (Meta-Analysis)
Meta-Analysis
Status epilepticus (SE) is a common neurologic emergency. The present study constitutes a meta-analysis of published randomized control trials (RCTs) evaluating the use of intravenous sodium valproate (VPA) in SE. MEDLINE and Cochrane databases were comprehensively searched, while retrieved RCTs and meta-analyses were manually screened. Prespecified outcome measures included seizure-cessation, 24 h-efficacy, constitute (liver enzyme increase, arrhythmias, bone-marrow suppression, hypotension and respiratory depression) and severe (life-threatening) adverse events (AEs). Evidence synthesis was performed when appropriate, using Random-Effects (RE) or Fixed-Effects (FE) model based on heterogeneity between trials (homogeneity assumed when PQ > 0.1 and I < 50%). Outcomes were assessed using Odds-Ratios (ORs) and 95%Confidence-Intervals (95% CIs). Every available comparison was investigated in terms of efficacy and tolerability.Thirteen studies were retrieved and five comparisons were available, four of which involved two or more studies. Results were compatible with no significant difference between VPA and Phenytoin both in terms of efficacy and tolerability [seizure-cessation: FE-OR = 1.99, 95% CI = (0.83-4.75), 24 h-efficacy: FE-OR = 1.32, 95% CI = (0.60-2.89), composite AEs: FE-OR = 0.45, 95% CI = (0.17-1.21)]. Phenobarbital proved more commonly associated with composite AEs than VPA [seizure-cessation: RE-OR = 0.68, 95% CI = (0.05-9.44), 24 h-efficacy: RE-OR = 0.88, 95% CI = (0.02-33.9), composite AEs: FE-OR = 0.26, 95% CI = (0.09-0.82), severe AEs: FE-OR = 0.30, 95% CI = (0.04-2.28)]. Diazepam was determined inferior to VPA concerning safety issues [seizure-termination: FE-OR = 0.77, 95% CI = (0.34-1.79), severe respiratory depression: FE-OR = 0.06, 95% CI = (0.01-0.48), severe hypotension: FE-OR = 0.09, 95% CI = (0.01-0.72)]. The combination of Lorazepam (LZP) with VPA and the combination of LZP with Levetiracetam presented no difference in efficacy [24h-efficacy: FE-OR = 0.68, 95% CI = (0.37-1.24)]. Although, additional high-quality RCTs are warranted, according to our results, VPA can be considered a safe and effective option in the management of SE.
Topics: Administration, Intravenous; Anticonvulsants; Humans; Randomized Controlled Trials as Topic; Status Epilepticus; Valproic Acid
PubMed: 32075481
DOI: 10.1080/00207454.2020.1732967 -
Medicine Jan 2020Sedoanalgesia secondary iatrogenic withdrawal syndrome (IWS) in paediatric intensive units is frequent and its assessment is complex. Therapies are heterogeneous, and...
BACKGROUND
Sedoanalgesia secondary iatrogenic withdrawal syndrome (IWS) in paediatric intensive units is frequent and its assessment is complex. Therapies are heterogeneous, and there is currently no gold standard method for diagnosis. In addition, the assessment scales validated in children are scarce. This paper aims to identify and describe both the paediatric diagnostic and assessment tools for the IWS and the treatments for the IWS in critically ill paediatric patients.
METHODS
A systematic review was conducted according to the PRISMA guidelines. This review included descriptive and observational studies published since 2000 that analyzed paediatric scales for the evaluation of the iatrogenic withdrawal syndrome and its treatments. The eligibility criteria included neonates, newborns, infants, pre-schoolers, and adolescents, up to age 18, who were admitted to the paediatric intensive care units with continuous infusion of hypnotics and/or opioid analgesics, and who presented signs or symptoms of deprivation related to withdrawal and prolonged infusion of sedoanalgesia.
RESULTS
Three assessment scales were identified: Withdrawal Assessment Tool-1, Sophia Observation Withdrawal Symptoms, and Opioid and Benzodiazepine Withdrawal Score. Dexmedetomidine, methadone and clonidine were revealed as options for the treatment and prevention of the iatrogenic withdrawal syndrome. Finally, the use of phenobarbital suppressed symptoms of deprivation that are resistant to other drugs.
CONCLUSIONS
The reviewed scales facilitate the assessment of the iatrogenic withdrawal syndrome and have a high diagnostic quality. However, its clinical use is very rare. The treatments identified in this review prevent and effectively treat this syndrome. The use of validated iatrogenic withdrawal syndrome assessment scales in paediatrics clinical practice facilitates assessment, have a high diagnostic quality, and should be encouraged, also ensuring nurses' training in their usage.
Topics: Child; Humans; Iatrogenic Disease; Intensive Care Units, Pediatric; Substance Withdrawal Syndrome
PubMed: 32000360
DOI: 10.1097/MD.0000000000018502 -
Neurology Jan 2020To review systematically community-based primary care interventions for epilepsy in low- and middle-income countries to rationalize approaches and outcome measures in...
OBJECTIVE
To review systematically community-based primary care interventions for epilepsy in low- and middle-income countries to rationalize approaches and outcome measures in relation to epilepsy care in these countries.
METHODS
A systematic search of PubMed, EMBASE, Global Index Medicus, CINAHL, and Web of Science was undertaken to identify trials and implementation of provision of antiseizure medications, adherence reinforcement, and/or health care provider or community education in community-based samples of epilepsy. Data on populations addressed, interventions, and outcomes were extracted from eligible articles.
RESULTS
The 24 reports identified comprise mostly care programs addressing active convulsive epilepsy. Phenobarbital has been used most frequently, although other conventional antiseizure medications (ASMs) have also been used, but none of the newer. Tolerability rates in these studies are high, but overall attrition is considerable. Other approaches include updating primary health care providers, reinforcing treatment adherence in clinics, and raising community awareness. In these programs, the coverage of existing treatment gap in the community, epilepsy-related mortality, and comorbidity burden are only fleetingly addressed. None, however, explicitly describe sustainability plans.
CONCLUSIONS
Cost-free provision, mostly of phenobarbital, has resulted in short-term seizure freedom in roughly half of the people with epilepsy in low- and middle-income countries. Future programs should include a range of ASMs. These should cover apart from seizure control and treatment adherence, primary health care provider education, community awareness, and referral protocols for specialist care. Programs should incorporate impact assessment at the local level. Sustainability in the long term as much as resilience and scalability should be addressed in future initiatives.
Topics: Community Health Services; Developing Countries; Epilepsy; Humans; Primary Health Care
PubMed: 31919114
DOI: 10.1212/WNL.0000000000008839 -
Psychological Medicine Nov 2020Comparisons of antipsychotics with placebo can be biased by unblinding due to side effects. Therefore, this meta-analysis compared the efficacy of antipsychotics for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Comparisons of antipsychotics with placebo can be biased by unblinding due to side effects. Therefore, this meta-analysis compared the efficacy of antipsychotics for acute schizophrenia in trials using barbiturates or benzodiazepines as active placebos.
METHODS
Randomized controlled trials (RCTs) in acute schizophrenia with at least 3 weeks duration and comparing any antipsychotic with barbiturates or benzodiazepines were eligible. ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, PubMed, WHO-ICTRP as well as previous reviews were searched up to 9 January 2018. Two separate meta-analyses, one for barbiturates and one for benzodiazepines, were conducted using random-effects models. The primary outcome was response to treatment, and mean values of schizophrenia rating scales and dropouts were analyzed as secondary outcomes. This study is registered with PROSPERO (CRD42018086263).
RESULTS
Seven barbiturate-RCTs (number of participants n = 1736), and two benzodiazepine-RCTs (n = 76) were included in the analysis. The studies were published between 1960 and 1968 and involved mainly chronically ill patients. More patients on antipsychotics in comparison to barbiturates achieved a 'good' response (36.2% v. 16.8%; RR 2.15; 95% CI 1.36-3.41; I2 = 48.9) and 'any' response (57.4% v. 27.8%; RR 2.07; 95% CI 1.35-3.18; I2 = 68.2). In a single small trial (n = 60), there was no difference between antipsychotics and benzodiazepines on 'any' response (74.7% v. 65%; RR 1.15; 95% CI 0.82-1.62).
CONCLUSIONS
Antipsychotic drugs were more efficacious than barbiturates, based on a large sample size. Response ratios were similar to those observed in placebo-controlled trials. The results on benzodiazepines were inconclusive due to the small number of studies and participants.
Topics: Antipsychotic Agents; Barbiturates; Benzodiazepines; Humans; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 31625485
DOI: 10.1017/S003329171900285X -
Epilepsy & Behavior : E&B Dec 2019The aim of this study was to estimate the comparative efficacy and safety of antiepileptic drugs (AEDs) in adults with benzodiazepine-resistant convulsive status... (Meta-Analysis)
Meta-Analysis
AIM
The aim of this study was to estimate the comparative efficacy and safety of antiepileptic drugs (AEDs) in adults with benzodiazepine-resistant convulsive status epilepticus (SE).
METHODS
MEDLINE, CENTRAL, ClinicalTrials.gov, and Opengrey.eu were searched (from inception to 3rd April, 2018) for randomized controlled trials (RCTs) of AEDs used intravenously to treat benzodiazepine-resistant SE in adults. Efficacy outcomes were SE cessation within 1 h from drug administration and seizure freedom at 24 h. Safety outcomes were respiratory depression and hypotension. Effect sizes were estimated by network meta-analyses within a frequentist framework. The hierarchy of competing interventions was established using the surface under the cumulative ranking curve (SUCRA) and mean ranks.
RESULTS
Five RCTs were considered, involving 349 patients. Included interventions were valproate (VPA; 20-30 mg/kg), phenytoin (PHT; 20 mg/kg), diazepam (DZP; 0.2 mg/kg, then 4 mg/h), phenobarbital (PHB; 20 mg/kg, then 100 mg every 6 h), lacosamide (LCM; 400 mg), and levetiracetam (LEV; 20 mg/kg); PHB was superior to PHT, VPA, DZP, LEV, and LCM with respect to SE cessation and performed better than VPA, DZP, and LCM in the achievement of seizure freedom at 24 h. No differences were noted between drugs in the occurrence of respiratory depression and hypotension. According to SUCRA, PHB had the greatest probabilities of being best in the achievement of SE control and seizure freedom, whereas VPA and LCM ranked best for the safety outcomes.
CONCLUSIONS
Our study suggests that high-dose PHB is effective in controlling SE and preventing seizure recurrence, and LCM and VPA could be better tolerated options. Further head-to-head comparative studies are strongly required to provide more definitive evidence. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".
Topics: Administration, Intravenous; Adult; Anticonvulsants; Benzodiazepines; Drug Resistant Epilepsy; Humans; Network Meta-Analysis; Prohibitins; Seizures; Status Epilepticus
PubMed: 31462385
DOI: 10.1016/j.yebeh.2019.106466 -
Epilepsy & Behavior : E&B Mar 2020The objective of the study was to review the current epidemiological evidence about the relationship between epilepsy and increased risk of cardio- and cerebrovascular...
OBJECTIVE
The objective of the study was to review the current epidemiological evidence about the relationship between epilepsy and increased risk of cardio- and cerebrovascular events.
METHODS
We systematically searched MEDLINE (from inception to 19th October 2018) to identify population-based cohort studies evaluating the risk of subsequent stroke or myocardial infarction (MI) in patients with epilepsy without history of prior cerebrovascular disease in comparison with subjects without epilepsy.
RESULTS
A total of 16,641 records were screened, and 6 studies were included. Data on the risk of subsequent stroke and MI were provided by five and two studies, respectively. The adjusted hazard ratios (HRs) of subsequent ischemic stroke for patients with epilepsy ranged from 1.09 (95% confidence interval (CI): 1.00-1.19) to 2.85 (95% CI: 2.49-3.26). Two studies assessing the incidence of hemorrhagic stroke showed an increased risk in patients with epilepsy (HR: 3.30; 95% CI: 2.46-4.43 and HR: 2.27; 95% CI: 1.80-2.85). The HRs of subsequent MI ranged between 1.09 (95% CI: 1.00 to 1.19) and 1.48 (95% CI: 1.31-1.67). Age, hypertension, MI, diabetes, hyperlipidemia, and arteriosclerosis were significantly associated with the increase in stroke risk. A gradient between the antiepileptic drug (AED) dose and risk of subsequent stroke was found. In comparison with carbamazepine (CBZ), oxcarbazepine (OXC) was associated with an increased risk of stroke and valproate (VPA) with a reduction in risk of stroke and MI, whereas no significant associations with vascular disease were found for phenobarbital (PB), lamotrigine (LMT), phenytoin (PHT), clonazepam (CLZ), and clobazam (CLB).
CONCLUSIONS
Patients with epilepsy are at higher risk of subsequent stroke and MI in comparison with subjects without epilepsy. Although individual AEDs may carry different risks of cardio- and cerebrovascular disease, the clinical relevance of the metabolic effects of the enzyme-inducing AEDs is still uncertain. This article is part of the Special Issue "Seizures & Stroke".
Topics: Anticonvulsants; Cohort Studies; Epilepsy; Humans; Myocardial Infarction; Population Surveillance; Risk Factors; Stroke
PubMed: 31182394
DOI: 10.1016/j.yebeh.2019.05.005 -
Daru : Journal of Faculty of Pharmacy,... Jun 2019Neonatal abstinence syndrome (NAS) which is observed in 55-94% of the newborns from opioids-taking mothers produces deleterious neurological symptoms. Various... (Review)
Review
Neonatal abstinence syndrome (NAS) which is observed in 55-94% of the newborns from opioids-taking mothers produces deleterious neurological symptoms. Various pharmacological therapies have been investigated in neonates with NAS. This article reviews all studies on NAS treatment to analyze the duration of treatment, length of hospitalization and possible drug adverse effects. The search was limited to the randomized clinical trials which examined the treatments of neonates with NAS. Scientific databases including PubMed, Cochrane Library, ISI Web of Science, Embase and Scopus were systematically searched. Retrieved articles were reviewed by two researchers and evaluated using the JADAD scoring system. Finally, the treatment duration, hospitalization length and drug side-effects were extracted. Methadone, buprenorphine and clonidine were found more effective than morphine. Diluted tincture of opium (DTO) in combination with phenobarbital or clonidine was significantly more effective than DTO alone. Clonidine was a significantly better adjunctive therapy than phenobarbital in reducing morphine treatment days. No significant difference was observed between morphine and DTO effectiveness. Deciding the optimal regimen to manage symptomatic NAS, as a single or an adjunct therapy is not possible based on the literature, due to the low quality, small size and short-term treatment considered in the published studies. Graphical abstract Process of selecting trials included in the present systematic review.
Topics: Analgesics, Opioid; Buprenorphine; Clonidine; Drug Therapy, Combination; Humans; Infant, Newborn; Length of Stay; Methadone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 31093953
DOI: 10.1007/s40199-019-00266-3 -
Neurology May 2019Compare the cost and effectiveness of nonbenzodiazepine antiepileptic drugs (non-BZD AEDs) for treatment of BZD-resistant convulsive status epilepticus (SE). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Compare the cost and effectiveness of nonbenzodiazepine antiepileptic drugs (non-BZD AEDs) for treatment of BZD-resistant convulsive status epilepticus (SE).
METHODS
Decision analysis model populated with effectiveness data from a systematic review and meta-analysis of the literature, and cost data from publicly available prices. The primary outcome was cost per seizure stopped ($/SS). Sensitivity analyses evaluated the robustness of the results across a wide variation of the input parameters.
RESULTS
We included 24 studies with 1,185 SE episodes. The most effective non-BZD AED was phenobarbital (PB) with a probability of SS of 0.8 (95% confidence interval [CI]: 0.69-0.88), followed by valproate (VPA) (0.71 [95% CI: 0.61-0.79]), lacosamide (0.66 [95% CI: 0.51-0.79]), levetiracetam (LEV) (0.62 [95% CI: 0.5-0.73]), and phenytoin/fosphenytoin (PHT) (0.53 [95% CI: 0.39-0.67]). In pairwise comparisons, PB was more effective than PHT ( = 0.002), VPA was more effective than PHT ( = 0.043), and PB was more effective than LEV ( = 0.018). The most cost-effective non-BZD AED was LEV (incremental cost-effectiveness ratio [ICER]: $18.55/SS), followed by VPA (ICER: $94.44/SS), and lastly PB (ICER: $847.22/SS). PHT and lacosamide were not cost-effective compared to the other options. Sensitivity analyses showed marked overlap in cost-effectiveness, but PHT was consistently less cost-effective than LEV, VPA, and PB.
CONCLUSION
VPA and PB were more effective than PHT for SE. There is substantial overlap in the cost-effectiveness of non-BZD AEDs for SE, but available evidence does not support the preeminence of PHT, neither in terms of effectiveness nor in terms of cost-effectiveness.
Topics: Anticonvulsants; Benzodiazepines; Cost-Benefit Analysis; Decision Support Techniques; Humans; Lacosamide; Levetiracetam; Phenobarbital; Phenytoin; Status Epilepticus; Treatment Failure; Valproic Acid
PubMed: 31068480
DOI: 10.1212/WNL.0000000000007503