Pharmacological treatment of neonatal seizures: a systematic review.
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ABSTRACT:
SUBMITTER: Slaughter LA
PROVIDER: S-EPMC3805825 | biostudies-other | 2013 Mar
REPOSITORIES: biostudies-other
Publications
Pharmacological treatment of neonatal seizures: a systematic review.
Slaughter Laurel A LA Patel Anup D AD Slaughter Jonathan L JL
Journal of child neurology 20130114 3
Pharmacologic treatment options for neonatal seizures have expanded over the past 2 decades, and there is no consensus on optimal treatment strategy. We systematically reviewed the published literature to determine which medication(s) are most effective for treating neonatal seizures, by retrieving trials and observational investigations via PubMed (through August 2011) that focused on pharmacological seizure treatment of neonates (≤ 28 days old) and utilized continuous or amplitude-integrated E ...[more]
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Project description:Introduction:Seizures are one of the most common neurological disorders of neonates, which is also an emergency in the neonatal intensive care unit. For neonates, the recommended first-line antiepileptic drugs (AEDs) include phenobarbitone, which may be effective in only 50% of seizures. Some new AEDs, such as levetiracetam, have been shown to be effective in adults and older children. However, their efficacy for neonatal seizures remains uncertain. The aim of this investigation is to conduct a systematic review to evaluate the efficacy of all AEDs in neonates. Additionally, the long-term outcomes following neonatal seizures, in relation to the development of cerebral palsy and epilepsy, will be studied. Method:We will perform a systematic review including randomised controlled studies (RCTs), cohort studies, case-controlled studies and case series studies which evaluated the efficacy of AEDs and short-term and long-term outcomes in neonatal seizures. PubMed, Embase, Web of Science, Cochrane Library and Clinical trial.gov will be searched. There will be no language restriction. Risk bias in RCTs will be evaluated by the Cochrane risk-of-bias tool, while cohort and case-control studies will be evaluated by the Newcastle-Ottawa Scale. A network meta-analysis will be performed by the Bayesian model using WinBUGS V.1.4.3 and R software if there is a high degree of homogeneity among studies. Otherwise, we will perform a narrative review without pooling. Subgroup analyses will be performed in different AEDs and dosage groups. Outcome:The primary outcomes will be seizure cessation confirmed by electroencephalogram and long-term neurodevelopmental outcome. Secondary outcomes will be neonatal mortality during hospitalisation and suspected drug toxicity. Ethics and dissemination:Formal ethical approval is not required as no primary data are collected. This systematic review will be disseminated through a peer-reviewed publication.
| S-EPMC7326240 | biostudies-literature
Project description:Background: Some patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported to exhibit neurological symptoms such as seizures and impaired consciousness. Our study reviews reported cases to assess the pharmacological approach to managing seizures in SARS-CoV-2 patients and associated outcomes. Methods: A systematic review of case reports on the incidence of seizures following coronavirus disease 2019 (COVID-19) among patients that reported use of antiepileptic drugs (AEDs) in management was performed by using the PRISMA (preferred reporting items for systematic reviews and meta-analysis) guidelines. Databases used included EMBASE, PubMed, SCOPUS, and Google Scholar. Data was presented as qualitative and descriptive data. Results: In total, 67 articles were selected for full-text assessment, of which 18 were included in the final review. Patients had a median age of 54 years, most of whom were male. Remdisivir, dexamethasone, Laninamivir, hydroxychloroquine, azithromycin, and Lopinavir-ritonavir were common agents used in the management of COVID-19. Most patients presented with either generalized tonic-clonic seizures or status epilepticus. Most patients received levetiracetam as drug choice or as part of their regimen. Other AEDs commonly prescribed included midazolam and sodium valproate. Some patients received no antiepileptic drug therapy. Most of the patients who died had more than one comorbidity. Also, most of the patients who died received COVID-19 treatment drugs. None of the patients who received midazolam as drug choice or as part of their regimen developed recurrent seizures in contrast to patients who received levetiracetam and sodium valproate as drug choice or as part of their regimen. Interestingly, none of the patients who received no AEDs suffered recurrent seizures or died. Conclusions: Standard guidelines for managing seizures in COVID-19 patients may be required. A limitation of this review is that it involved the use of case reports with no controls and a small number of patients.
| S-EPMC9648370 | biostudies-literature
Project description:Background: Pharmacological treatment is of great importance in forensic psychiatry, and the vast majority of patients are treated with antipsychotic agents. There are several systematic differences between general and forensic psychiatric patients, e.g. severe violent behavior, the amount of comorbidity, such as personality disorders and/or substance abuse. Based on that, it is reasonable to suspect that effects of pharmacological treatments also may differ. The objective of this systematic review was to investigate the effects of pharmacological interventions for patients within forensic psychiatry. Methods: The systematic review protocol was pre-registered in PROSPERO (CRD42017075308). Six databases were used for literature search on January 11, 2018. Controlled trials from forensic psychiatric care reporting on the effects of antipsychotic agents, mood stabilizers, benzodiazepines, antidepressants, as well as pharmacological agents used for the treatment of addiction or ADHD, were included. Two authors independently reviewed the studies, evaluated risk of bias and assessed certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: The literature search resulted in 1783 records (titles and abstracts) out of which 10 studies were included. Most of the studies included were retrospective and non-randomized. Five of them focused on treatment with clozapine and the remaining five on other antipsychotics or mood stabilizers. Five studies with a high risk of bias indicated positive effects of clozapine on time from treatment start to discharge, crime-free time, time from discharge to readmission, improved clinical functioning, and reduction in aggressive behavior. Psychotic symptoms after treatment were more pronounced in the clozapine group. Mainly due to the high risk of bias the reliability of the evidence for all outcomes was assessed as very low. Conclusion: This systematic review highlights the shortage of knowledge on the effectiveness of pharmacological treatment within forensic psychiatry. Due to very few studies being available in this setting, as well as limitations in their execution and reporting, it is challenging to overview the outcomes of pharmacological interventions in this context. The frequent use of antipsychotics, sometimes in combination with other pharmacological agents, in this complex and heterogeneous patient group, calls for high-quality studies performed in this specific setting.
| S-EPMC6976536 | biostudies-literature
Project description:ImportanceIncidence of neonatal abstinence syndrome is rising rapidly, and optimal pharmacotherapy may meaningfully reduce length of treatment.ObjectiveTo compare pharmacological therapies for neonatal abstinence syndrome.Data sourcesSystematic 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 selectionRandomized 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 synthesisData 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 measuresThe primary outcome was the length of treatment. The length of stay, need for adjuvant therapy, and adverse events were considered as secondary outcomes.ResultsEighteen 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 relevanceThe 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.
| S-EPMC6439896 | biostudies-literature
Project description:BackgroundStimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on amphetamines (AMPH) or methamphetamine (MA) is a growing global concern. Yet, there is no established pharmacotherapy for AMPH/MA dependence. A comprehensive assessment of the research literature on pharmacotherapy for AMPH/MA dependence may inform treatment guidelines and future research directions.MethodsWe systematically reviewed the peer-reviewed literature via the electronic databases PubMed, EMBASE, CINAHL and SCOPUS for randomised controlled trials reported in the English language examining a pharmacological treatment for AMPH/MA dependence or use disorder. We included all studies published to 19 June 2019. The selected studies were evaluated for design; methodology; inclusion and exclusion criteria; sample size; pharmacological and (if included) psychosocial interventions; length of follow-up and follow-up schedules; outcome variables and measures; results; overall conclusions and risk of bias. Outcome measures were any reported impact of treatment related to AMPH/MA use.ResultsOur search returned 43 studies that met our criteria, collectively enrolling 4065 participants and reporting on 23 individual pharmacotherapies, alone or in combination. Disparate outcomes and measures (n = 55 for the primary outcomes) across studies did not allow for meta-analyses. Some studies demonstrated mixed or weak positive signals (often in defined populations, e.g. men who have sex with men), with some variation in efficacy signals dependent on baseline frequency of AMPH/MA use. The most consistent positive findings have been demonstrated with stimulant agonist treatment (dexamphetamine and methylphenidate), naltrexone and topiramate. Less consistent benefits have been shown with the antidepressants bupropion and mirtazapine, the glutamatergic agent riluzole and the corticotropin releasing factor (CRF-1) antagonist pexacerfont; whilst in general, antidepressant medications (e.g. selective serotonin reuptake inhibitors [SSRIs], tricyclic antidepressants [TCAs]) have not been effective in reducing AMPH/MA use.ConclusionsNo pharmacotherapy yielded convincing results for the treatment of AMPH/MA dependence; mostly studies were underpowered and had low treatment completion rates. However, there were positive signals from several agents that warrant further investigation in larger scale studies; agonist therapies show promise. Common outcome measures should include change in use days. Future research must address the heterogeneity of AMPH/MA dependence (e.g. coexisting conditions, severity of disorder, differences between MA and AMPH dependence) and the role of psychosocial intervention.
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Project description:AimThe 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.MethodWe 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.ResultsOur 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.InterpretationOur 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.
| S-EPMC8028713 | biostudies-literature
Project description:Background: Neonatal seizures are a common neurological emergency in newborns. Phenobarbital (PB) is the first-line antiepileptic drug (AED). However, PB has some side effects, such as hypotension and respiratory depression, and it can accelerate neuronal apoptosis in the immature brain. Levetiracetam (LEV), a new antiepileptic drug, has been used as a second-line drug for the treatment of neonatal seizures. Compared with PB, LEV has many advantages, including a low incidence of side effects and better neurodevelopmental outcomes. However, there are only a few systematic reviews of LEV for the treatment of neonatal seizures. Objective: To evaluate the efficacy and safety of LEV for neonatal seizures and to compare the efficacy, side effects, and neurological outcomes between LEV and PB in the treatment of neonatal seizures. Methods: The keywords LEV, PB, and neonatal seizure were searched in the MEDLINE, Cochrane Library, Web of Science, EMBASE, clinicaltrials.gov, and China National Knowledge Internet (CNKI) databases with a last update in July 2021 to collect high-quality studies. We collected studies studying the efficacy or safety of LEV and PB in the treatment of neonatal seizures applying strict inclusion and exclusion criteria. The data were extracted and outcome measures, including efficacy, side effect rate, neurological score, and mortality rate, were analyzed with RevMan 5.3 software. Results: Ten articles were finally included in the meta-analysis. The meta-analysis showed that there was no difference in efficacy between LEV and PB in the treatment of neonatal seizures. Compared with PB, the incidence of side effects of LEV was lower. The incidence of hypotension and respiratory depression in the LEV group was significantly lower than that in the PB group. In terms of long-term neurodevelopmental outcomes, there was no significant difference in the Bayley Scales of Infant Development (BSID) scores between LEV and PB. Conclusion: PB is still the first-line AED recommended by the WHO for the treatment of neonatal seizures. The new AEDs LEV may not have better efficacy than PB. At the same time, LEV is associated with better neurodevelopment outcomes and a lower risk of adverse effects. In addition, continuous EEG monitoring should be used to diagnose neonatal seizures to evaluate the severity of the seizures, remission, and drug efficacy. Systematic Review Registration: PROSPERO, identifier: CRD42021279029.
| S-EPMC8636327 | biostudies-literature
Project description:BackgroundPediatric glioblastoma (GBM) is an aggressive central nervous system tumor in children that has dismal prognosis. Standard of care is surgery with subsequent irradiation and temozolomide. We aimed to outline currently available data on novel pharmacological treatments for pediatric GBM.MethodsWe conducted a systematic literature search in PubMed and Embase, including reports published in English from 2010 to 2021. We included randomized trials, cohort studies and case series. Phase I trials were not analyzed. We followed PRISMA guidelines, assessed the quality of the eligible reports using the Newcastle-Ottawa scale (NOS) and the RoB-2 tool and registered the protocol on PROSPERO.ResultsWe included 6 out of 1122 screened reports. All six selected reports were prospective, multicenter phase II trials (five single-arm and one randomized controlled trial). None of the investigated novel treatment modalities showed any benefit regarding overall or progression free survival.ConclusionsTo date, the role of pharmacological approaches regarding pediatric GBM remains unclear, since no novel treatment approach could provide a significant impact on overall or progression free survival. Further research should aim to combine different treatment strategies in large international multicenter trials with central comprehensive diagnostics regarding subgrouping. These novel treatment approaches should include targeted and immunotherapeutic treatments, potentially leading to a more successful outcome.
| S-EPMC9179254 | biostudies-literature
Project description:IntroductionDepression is a serious and widespread mental health disorder. Although effective treatment does exist, a significant proportion of patients with depression fail to respond to antidepressant treatment trials, a condition named treatment-resistant depression. Efficient approach should be given this condition in order to revert the burden caused by depression. Clinical practice guidelines (CPGs) are evidence-based health promotion instruments to improve diagnosis and treatment. CPGs recommendations for treatment-resistant depression must be trustworthy. The objective of the proposed study is to systematically identify, appraise the quality of CPGs for the treatment of depression and elaborate a synthesis of recommendations for treatment-resistant depression of CPGs considered to be of high quality and with high quality recommendations.Methods and analysisWe will search the databases of organizations, such as PubMed, Embase, Cochrane Library, PsycInfo, and the Virtual Health Library, and organizations that develop CPGs. Three independent researchers will assess the quality of the CPGs and their recommendations using the AGREE II and AGREE-REX instruments, respectively. Given the identification of divergences and convergences as well as weak and strong points among high quality CPGs, our work may help developers, clinicians and eventually patients.Ethics and disseminationNo ethical approval is required for a systematic review, as no patient data will be used. The research results will be disseminated in conferences and submitted to a peer reviewed journal.
| S-EPMC9017892 | biostudies-literature
Project description:Seizures are the most frequent neurological clinical symptoms of the central nervous system (CNS) during the neonatal period. Neonatal seizures may be ascribed to an acute event or symptomatic conditions determined by genetic, metabolic or structural causes, outlining the so-called 'Neonatal Epilepsies'. To date, three main groups of neonatal epilepsies are recognised during the neonatal period: benign familial neonatal epilepsy (BFNE), early myoclonic encephalopathy (EME) and 'Ohtahara syndrome' (OS). Recent advances showed the role of several genes in the pathogenesis of these conditions, such as KCNQ2, KCNQ3, ARX, STXBP1, SLC25A22, CDKL5, KCNT1, SCN2A and SCN8A. Herein, we reviewed the current knowledge regarding the pathogenic variants most frequently associated with neonatal seizures, which should be considered when approaching newborns affected by these disorders. In addition, we considered the new possible therapeutic strategies reported in these conditions.
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