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1.
Medicine (Baltimore) ; 99(17): e18704, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332593

RESUMO

BACKGROUND: Hypoxic ischemic encephalopathy (HIE) is brain injury caused by different reasons and the most common diagnosed is neonatal HIE. Most of the existing treatments have their own shortcomings or there are still some unexplained mechanisms in it. Topiramate (TPM) is a new drug for the treatment for seizures in neonates with HIE, but is currently used off-label. Our protocol aims to access the efficiency and safety of TPM for HIE. METHODS AND ANALYSIS: Eight databases will be searched by 2 independent researchers for the article on the topic of using TPM as treatment for HIE, including PubMed, the Cochrane Central Register of Controlled Trials (Cochrane Library), Embase, and Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wang Fang Database and Chinese Science and Technology Periodical database (VIP). The included papers are those published from the established date of the databases to 2019. The therapeutic effects based on the grade of neonatal behavioral neurological assessment will be regarded as the primary outcomes. RevMan V5.3 will be used to compute the data synthesis and carry out meta-analysis. The risk of bias will be appraised by the Cochrane risk of bias tool. Rare ratio for dichotomous outcomes and mean different for continuous data will be expressed with 95% confidence intervals (CI) for analysis. A random effects model or a fixed effects model will be employed, when heterogeneity is found or not. Subgroup analysis and sensitivity analysis will be applied if the heterogeneity is obvious. RESULTS: This study will provide the recent evidence of TPM for HIE from reducing seizure acticity. CONCLUSION: The conclusion of this study will provide proof to evaluate if TPM is effective and safe in the treatment of HIE.PROSPERO registration number: PROSPERO CRD42018117981.


Assuntos
Anticonvulsivantes/uso terapêutico , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Topiramato/uso terapêutico , Anticonvulsivantes/efeitos adversos , Humanos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/mortalidade , Recém-Nascido , Estresse Oxidativo/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Convulsões/tratamento farmacológico , Convulsões/etiologia , Índice de Gravidade de Doença , Topiramato/efeitos adversos
2.
J Headache Pain ; 20(1): 92, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470791

RESUMO

BACKGROUND: Chronic migraine is a disabling condition that is currently underdiagnosed and undertreated. In this narrative review, we discuss the future of chronic migraine management in relation to recent progress in evidence-based pharmacological treatment. FINDINGS: Patients with chronic migraine require prophylactic therapy to reduce the frequency of migraine attacks, but the only currently available evidence-based prophylactic treatment options for chronic migraine are topiramate and onabotulinumtoxinA. Improved prophylactic therapy is needed to reduce the high burden of chronic migraine in Italy. Monoclonal antibodies that target the calcitonin gene-related peptide (CGRP) pathway of migraine pathogenesis have been specifically developed for the prophylactic treatment of chronic migraine. These anti-CGRP/R monoclonal antibodies have demonstrated good efficacy and excellent tolerability in phase II and III clinical trials, and offer new hope to patients who are currently not taking any prophylactic therapy or not benefitting from their current treatment. CONCLUSIONS: Treatment of chronic migraine is a dynamic and rapidly advancing area of research. New developments in this field have the potential to improve the diagnosis and provide more individualised treatments for this condition. Establishing a culture of prevention is essential for reducing the personal, social and economic burden of chronic migraine.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Toxinas Botulínicas Tipo A/uso terapêutico , Doença Crônica , Pessoas com Deficiência , Humanos , Transtornos de Enxaqueca/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Topiramato/uso terapêutico
3.
J Headache Pain ; 20(1): 88, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416424

RESUMO

BACKGROUND: Migraine diagnosis is based on clinical aspects and is dependent on the experience of the attending physician. This study aimed to describe the patients journey profile until they start their experience in a tertiary headache center. METHODS: In a cross-sectional study, medical charts from migraine patients were reviewed to describe which treatments, procedures and follow-up strategies are performed until the first appointment with a headache specialist. Patients from both sexes, ≥18 years old, which came to their first visit from March to July 2017 were included. Sociodemographic information, headache characteristics, diagnostic methods previously used, clinical history, family history and the treatments previously used were assessed in the first appointment with a specialist. Patient Health Questionnaire-9 and General Anxiety Disorder-7 were also applied. Descriptive analyses were performed to describe the sample profile and statistical tests were used to evaluate factors associated with the type of migraine (chronic or episodic). RESULTS: The sample consisted of 465 patients. On average, the pain started 17.1 (SD = 11.4) years before the first appointment with a headache specialist. Most of patients were classified as having chronic migraine (51.7%), with an average frequency of 15.5 (SD = 9.9) days per month. Regarding patients' journey until a specialist, most patients were submitted to laboratory tests (74.0%), cranial tomography (66.8%) and magnetic resonance imaging (66.8%) as diagnostic methods, and preventive drugs (70.2%) and acupuncture (61.0%) as treatments. After stratification by migraine type as episodic or chronic, patients with chronic migraine were submitted to more magnetic resonance imaging test, acupuncture, psychotherapy, used preventive drugs, and reported to have used topiramate without beneficial effects. CONCLUSIONS: Brazilian patients with migraine experiment a long journey until getting to a headache specialist and are submitted to a great number of unnecessary exams, especially those with chronic migraine.


Assuntos
Transtornos de Enxaqueca/terapia , Terapia por Acupuntura , Adolescente , Adulto , Estudos Transversais , Feminino , Cefaleia , Humanos , Masculino , Pessoa de Meia-Idade , Topiramato/uso terapêutico
4.
Expert Opin Pharmacother ; 20(16): 1971-1980, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31424287

RESUMO

Introduction: Restless Legs Syndrome/Willis-Ekbom disease (RLS/WED) is a common sensory-motor neurological disorder that impairs nocturnal rest causing decreased alertness, depressed mood, reduced job performance and poor quality of life. In patients affected by moderate to severe RLS/WED, a pharmacological treatment is mandatory. Areas covered: The present review is based on an extensive Internet and PubMed search from 1996 to 2019. It is focused on drugs currently used and under development (phase III and beyond) for the treatment of RLS/WED. Expert opinion: The drugs currently available for the treatment of the disease do not always allow for obtaining the optimal control of symptoms, in particular in the long-term treatment. Although initially effective, long-term dopaminergic treatment tends to wane over time and augmentation can occur. Updated international guidelines now recommend α2δ calcium channel ligand medications as the initial drug of choice. Oxycodone-naloxone demonstrated a significant and sustained treatment effect for patients with severe RLS/WED insufficiently controlled with previous treatments. Head-to-head trials of different drugs, as well as more studies on nondopaminergic agents and combination therapy, are greatly needed. Monoamine oxidase B inhibitors could be good candidates for the initial treatment of RLS/WED, sparing stronger dopaminergic agents for later stages of the disease.


Assuntos
Agonistas de Dopamina/uso terapêutico , Síndrome das Pernas Inquietas/tratamento farmacológico , Canais de Cálcio/química , Canais de Cálcio/metabolismo , Agonistas de Dopamina/química , Agonistas de Dopamina/metabolismo , Gabapentina/química , Gabapentina/metabolismo , Gabapentina/uso terapêutico , Humanos , Pramipexol/química , Pramipexol/metabolismo , Pramipexol/uso terapêutico , Pregabalina/química , Pregabalina/metabolismo , Pregabalina/uso terapêutico , Síndrome das Pernas Inquietas/patologia , Tetra-Hidronaftalenos/química , Tetra-Hidronaftalenos/metabolismo , Tetra-Hidronaftalenos/uso terapêutico , Tiofenos/química , Tiofenos/metabolismo , Tiofenos/uso terapêutico , Topiramato/química , Topiramato/metabolismo , Topiramato/uso terapêutico
6.
Continuum (Minneap Minn) ; 25(4): 959-975, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31356289

RESUMO

PURPOSE OF REVIEW: Tremor may be defined as an involuntary movement that is rhythmic (ie, regularly recurrent) and oscillatory (ie, rotating around a central plane) and may manifest in a variety of ways; accordingly, tremor has a rich clinical phenomenology. Consequently, the diagnosis of tremor disorders can be challenging, and misdiagnoses are common. The goal of this article is to provide the reader with straightforward approaches to the diagnosis and treatment of tremors. RECENT FINDINGS: Focused ultrasound thalamotomy of the ventral intermediate nucleus of the thalamus is an emerging and promising therapy for the treatment of essential tremor. SUMMARY: The evaluation should start with a detailed tremor history followed by a focused neurologic examination, which should attend to the many subtleties of tremor phenomenology. Among other things, the history and examination are used to establish whether the primary tremor is an action tremor (ie, postural, kinetic, or intention tremor) or a resting tremor. The clinician should then formulate two sets of diagnoses: disorders in which action tremor is the predominant tremor versus those in which resting tremor is the predominant tremor. Among the most common of the former type are essential tremor, enhanced physiologic tremor, drug-induced tremor, dystonic tremor, primary writing tremor, orthostatic tremor, and cerebellar tremor. Parkinson disease is the most common disorder of resting tremor. This article details the clinical features of each of these disorders, as well as those of additional tremor disorders.


Assuntos
Tremor/diagnóstico , Tremor/fisiopatologia , Idoso , Diagnóstico Diferencial , Distonia/diagnóstico , Distonia/fisiopatologia , Distonia/terapia , Tremor Essencial/diagnóstico , Tremor Essencial/fisiopatologia , Tremor Essencial/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Topiramato/uso terapêutico , Tremor/terapia , Núcleos Ventrais do Tálamo/cirurgia
7.
Int J Clin Pharm ; 41(4): 1056-1061, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31222537

RESUMO

Background Valproic acid is one of several antiepileptic medications requiring therapeutic drug monitoring due to its complex and wide pharmacokinetic interindividual variability. Objective The objective of this study was to determine the population pharmacokinetics of valproic acid in adult Saudi patients and to identify factors that explain its pharmacokinetic variability. Setting Tertiary referral teaching hospital, Riyadh, Saudi Arabia. Method A retrospective chart review was performed at King Saud University Medical City of patients who received oral valproic acid. The population pharmacokinetic models were developed using Monolix 4.4. After development of the base model, we investigated several covariates including age, sex, weight, total daily dose, and cotherapy with carbamazepine and phenytoin. Main outcome measures the pharmacokinetic parameters of valproic acid and the variables that contributing towards its inter-individual variability. Results The analysis included a total of 54 valproic acid plasma concentrations from 54 patients (42.5% male). The data were sufficiently described by a one-compartment model with linear absorption and elimination processes. Average parameter estimates for valproic acid apparent clearance (CL/F) and apparent volume of distribution (V/F) were 0.14 L/h and 37.7 L (fixed), respectively. The inter-individual variability (coefficients of variation) in CL/F was 12%. The most significant covariates for valproic acid CL/F were age, body weight, total daily dose, and cotherapy with carbamazepine and phenytoin. Conclusion This model showed significant inter-individual variability between subjects. Our findings showed that patient age, body weight, total daily dose, and cotherapy with carbamazepine and phenytoin are the most significant covariates of valproic acid clearance. Collectively, healthcare providers should take these factors in consideration for optimal valproic acid dosage regimen.


Assuntos
Taxa de Depuração Metabólica , Ácido Valproico/farmacocinética , Administração Oral , Adolescente , Adulto , Idoso , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Fenitoína/uso terapêutico , Estudos Retrospectivos , Arábia Saudita , Topiramato/uso terapêutico , Ácido Valproico/administração & dosagem , Ácido Valproico/sangue , Adulto Jovem
8.
Cochrane Database Syst Rev ; 6: CD012065, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31233229

RESUMO

BACKGROUND: This is an updated version of the original Cochrane Review published in Issue 12, 2016. This review is one in a series of Cochrane Reviews investigating pair-wise monotherapy comparisons.Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy, the majority of which may be able to achieve remission with a single antiepileptic drug (AED).The correct choice of first-line AED for individuals with newly diagnosed seizures is of great importance and should be based on the highest-quality evidence available regarding the potential benefits and harms of various treatments for an individual.Topiramate and carbamazepine are commonly used AEDs. Performing a synthesis of the evidence from existing trials will increase the precision of results of outcomes relating to efficacy and tolerability, and may help inform a choice between the two drugs. OBJECTIVES: To review the time to treatment failure, remission and first seizure with topiramate compared with carbamazepine when used as monotherapy in people with focal onset seizures (simple or complex focal and secondarily generalised), or generalised onset tonic-clonic seizures (with or without other generalised seizure types). SEARCH METHODS: For the latest update we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (Ovid); ClinicalTrials.gov; and the WHO International Clinical Trials Registry Platform (ICTRP) to 22 May 2018. We imposed no language restrictions. We also contacted pharmaceutical companies and trial investigators. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing monotherapy with either topiramate or carbamazepine in children or adults with focal onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types). DATA COLLECTION AND ANALYSIS: This was an individual participant data (IPD), review. Our primary outcome was time to treatment failure. Our secondary outcomes were time to first seizure post-randomisation, time to six-month remission, time to 12-month remission, and incidence of adverse events. We used Cox proportional hazards regression models to obtain trial-specific estimates of hazard ratios (HRs), with 95% confidence intervals (CIs), using the generic inverse variance method to obtain the overall pooled HR and 95% CI. MAIN RESULTS: IPD were available for 1151 of 1239 eligible individuals from two of three eligible studies (93% of the potential data). A small proportion of individuals recruited into these trials had 'unclassified seizures;' for analysis purposes, these individuals are grouped with those with generalised onset seizures. For remission outcomes, a HR < 1 indicated an advantage for carbamazepine, and for first seizure and treatment failure outcomes, a HR < 1 indicated an advantage for topiramate.The main overall results for the primary outcome, time to treatment failure, given as pooled HR adjusted for seizure type were: time to failure for any reason related to treatment 1.16 (95% CI 0.97 to 1.38); time to failure due to adverse events 1.02 (95% CI 0.82 to 1.27); and time to failure due to lack of efficacy 1.46 (95% CI 1.08 to 1.98). Overall results for secondary outcomes were time to first seizure 1.11 (95% CI 0.96 to 1.29); and time to six-month remission 0.88 (0.76 to 1.01). There were no statistically significant differences between the drugs. A statistically significant advantage for carbamazepine was shown for time to 12-month remission: 0.84 (95% CI 0.71 to 0.99).The results of this review are applicable mainly to individuals with focal onset seizures; 81% of individuals included within the analysis experienced seizures of this type at baseline. For individuals with focal onset seizures, a statistically significant advantage for carbamazepine was shown for time to failure for any reason related to treatment (HR 1.21, 95% CI 1.01 to 1.46), time to treatment failure due to lack of efficacy (HR 1.47, 95% CI 1.07 to 2.02), and time to 12-month remission (HR 0.82, 95% CI 0.69 to 0.99). There was no statistically significant difference between topiramate and carbamazepine for 'time to first seizure' and 'time to six-month remission'.Evidence for individuals with generalised tonic-clonic seizures (9% of participants contributing to the analysis), and unclassified seizure types (10% of participants contributing to the analysis) was very limited; no statistically significant differences were found but CIs were wide; therefore we cannot exclude an advantage to either drug, or a difference between drugs.The most commonly reported adverse events with both drugs were drowsiness or fatigue, "pins and needles" (tingling sensation), headache, gastrointestinal disturbance and anxiety or depression. The rate of adverse events was similar across the two drugs.We judged the methodological quality of the included trials generally to be good; however, there was some evidence that the open-label design of the larger of the two trials may have influenced the treatment failure rate within the trial. Hence, we judged the certainty of the evidence for treatment failure to be moderate for individuals with focal onset seizures and low for individuals with generalised onset seizures. For efficacy outcomes (first seizure, remission), we judged the certainty of evidence from this review to be high for individuals with focal onset seizures and moderate for individuals with generalised onset or unclassified seizures. AUTHORS' CONCLUSIONS: For individuals with focal onset seizures, there is moderate-certainty evidence that carbamazepine is less likely to be withdrawn and high-certainty evidence that 12-month remission will be achieved earlier than with topiramate. We did not find any differences between the drugs in terms of the other outcomes measured in the review and for individuals with generalised tonic-clonic seizures or unclassified epilepsy; however, we encourage caution in the interpretation of results including small numbers of participants with these seizure types.Future trials should be designed to the highest quality possible and take into consideration masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Epilepsia Tônico-Clônica/tratamento farmacológico , Topiramato/uso terapêutico , Adolescente , Adulto , Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Criança , Pré-Escolar , Epilepsia Generalizada/tratamento farmacológico , Feminino , Humanos , Quimioterapia de Indução , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Fatores de Tempo , Topiramato/efeitos adversos , Falha de Tratamento
9.
Bipolar Disord ; 21(7): 595-610, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31077521

RESUMO

OBJECTIVES: Substance use disorders (SUDs), including those for alcohol, stimulants, tobacco, opioids and cannabis, in patients with bipolar disorder are a major clinical and public health problem, and are present in the majority of these patients. Nonetheless, the development of effective pharmacological treatments for co-occurring SUDs in bipolar illness have not been well-developed and may be an important practical reason for the reduced effectiveness of these medications in community practice. METHODS: We conducted a systematic review of the literature (PubMed, Medline, Google Scholar), and identified N = 29 clinical studies, which evaluated both mental health and SUD outcomes in patients with co-occurring bipolar disorders and SUDs. RESULTS: Our findings suggest the potential of valproate sodium and lamotrigine as preferred pharmacological agents for the treatment of co-occurring psychiatric and substance use outcomes in these patients. However, many of the reviewed studies are of open-label designs and of modest sample sizes. CONCLUSIONS: Thus, given the gaps in our knowledge, recommendations for treatment of this common and important co-morbidity are preliminary. Accordingly, the conduct of larger, randomized controlled trials for this co-morbidity is clearly needed.


Assuntos
Anticonvulsivantes/uso terapêutico , Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/psicologia , Comorbidade , Humanos , Lamotrigina/uso terapêutico , Compostos de Lítio/uso terapêutico , Fumarato de Quetiapina/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias/psicologia , Topiramato/uso terapêutico , Ácido Valproico/uso terapêutico
10.
J Headache Pain ; 20(1): 39, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31014225

RESUMO

BACKGROUND: Some variables have been proposed as predictors of efficacy of OnabotulinumtoxinA in chronic migraine patients, but data available are inconclusive. We aimed to analyse the influence of single nucleotide polymorphisms in the response to OnabotulinumtoxinA. METHODS: We included 156 female patients treated with OnabotulinumtoxinA accordingly to PREEMPT paradigm in three headache units. OnabotulinumtoxinA was offered to patients that had not responded to topiramate and at least one other preventative. Age at first procedure was 43.7 ± 11.8 years (16-74). Patients with a reduction of at least 50% in the number of migraine days after two OnabotulinumtoxinA procedures were considered as responders. We analysed 25 polymorphisms selected for their relevance regarding migraine pathophysiology and their association with migraine according to previously published genome-wide association studies. Genotyping was performed using KASP probes and a LightCycler-480 (Roche-Diagnostics). Allelic, genotypic frequencies and dominance/recesivity hypothesis of the allelic variants were compared between responders and non-responders by Fisher's exact test. RESULTS: Response to treatment with OnabotulinumtoxinA was achieved in 120 patients (76,9%). Two polymorphisms showed differences: CALCA rs3781719, where allele C represents 26.9% in responders and 40.9% in non-responders (p = 0.007, OR = 3.11 (1.33-7.26)); and TRPV1 rs222749, where allele A represents 4.17% in responders and 12.5% in non-responders (p = 0.013, OR = 3.29 (1.28-8.43)). No significant differences in rest of polymorphisms or clinical or demographic variables were found. CONCLUSIONS: Polymorphic variations of CALCA and TRPV1 genes might play a role as prognostic markers of efficacy of OnabotulinumtoxinA in chronic migraine female patients in our population.


Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Peptídeo Relacionado com Gene de Calcitonina/genética , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/genética , Polimorfismo de Nucleotídeo Único/genética , Canais de Cátion TRPV/genética , Adolescente , Adulto , Idoso , Doença Crônica , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla/métodos , Humanos , Pessoa de Meia-Idade , Fármacos Neuromusculares/uso terapêutico , Estudos Prospectivos , Topiramato/uso terapêutico , Resultado do Tratamento , Adulto Jovem
11.
Clin Perinatol ; 46(2): 311-325, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010562

RESUMO

Neonatal brain injury (NBI) remains a major contributor to neonatal mortality and long-term neurodevelopmental morbidity. Although therapeutic hypothermia is the only proven treatment to minimize brain injury caused by neonatal encephalopathy in term neonates, it provides incomplete neuroprotection. There are no specific drugs yet proven to prevent NBI in preterm neonates. This review discusses the scientific and emerging clinical trial data for several neuroprotective drugs in development, examining potential efficacy and safety concerns. Drugs with the highest likelihood of success and closest to clinical application include erythropoietin for term and preterm neonates and antenatal magnesium for preterm neonates.


Assuntos
Hemorragia Cerebral Intraventricular/prevenção & controle , Hipóxia-Isquemia Encefálica/prevenção & controle , Leucomalácia Periventricular/prevenção & controle , Neuroproteção , Corticosteroides/uso terapêutico , Alopurinol/uso terapêutico , Anestésicos Inalatórios/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antioxidantes/uso terapêutico , Hemorragia Cerebral Intraventricular/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Darbepoetina alfa/uso terapêutico , Eritropoetina/uso terapêutico , Depuradores de Radicais Livres/uso terapêutico , Hematínicos/uso terapêutico , Humanos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Indometacina/uso terapêutico , Recém-Nascido , Leucomalácia Periventricular/tratamento farmacológico , Magnésio/uso terapêutico , Melatonina/uso terapêutico , Cuidado Pré-Natal , Topiramato/uso terapêutico , Xenônio/uso terapêutico
12.
PLoS One ; 14(3): e0212785, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30893319

RESUMO

BACKGROUND: Headaches are a common source of pain and suffering. The study's purpose was to assess beta-blockers efficacy in preventing migraine and tension-type headache. METHODS: Cochrane Register of Controlled Trials; MEDLINE; EMBASE; ISI Web of Science, clinical trial registries, CNKI, Wanfang and CQVIP were searched through 21 August 2018, for randomized trials in which at least one comparison was a beta-blocker for the prevention of migraine or tension-type headache in adults. The primary outcome, headache frequency per month, was extracted in duplicate and pooled using random effects models. DATA SYNTHESIS: This study included 108 randomized controlled trials, 50 placebo-controlled and 58 comparative effectiveness trials. Compared to placebo, propranolol reduced episodic migraine headaches by 1.5 headaches/month at 8 weeks (95% CI: -2.3 to -0.65) and was more likely to reduce headaches by 50% (RR: 1.4, 95% CI: 1.1-1.7). Trial Sequential Analysis (TSA) found that these outcomes were unlikely to be due to a Type I error. A network analysis suggested that beta-blocker's benefit for episodic migraines may be a class effect. Trials comparing beta-blockers to other interventions were largely single, underpowered trials. Propranolol was comparable to other medications known to be effective including flunarizine, topiramate and valproate. For chronic migraine, propranolol was more likely to reduce headaches by at least 50% (RR: 2.0, 95% CI: 1.0-4.3). There was only one trial of beta-blockers for tension-type headache. CONCLUSIONS: There is high quality evidence that propranolol is better than placebo for episodic migraine headache. Other comparisons were underpowered, rated as low-quality based on only including single trials, making definitive conclusions about comparative effectiveness impossible. There were few trials examining beta-blocker effectiveness for chronic migraine or tension-type headache though there was limited evidence of benefit. REGISTRATION: Prospero (ID: CRD42017050335).


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Propranolol/uso terapêutico , Cefaleia do Tipo Tensional/tratamento farmacológico , Topiramato/uso terapêutico , Ácido Valproico/uso terapêutico , Adulto , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Transtornos de Enxaqueca/fisiopatologia , Cefaleia do Tipo Tensional/fisiopatologia
13.
J Pak Med Assoc ; 69(3): 442-444, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30890845

RESUMO

Seizures are common in patients with brain tumours, even though prophylactic anti-seizure treatment for all patients with brain tumours is not recommended. Newer anti-epileptic drugs have shown benefits that outweigh the side effects of treatment and can also be given in combination with traditional anti-epileptic drugs. The authors have reviewed the literature on the various combinations of anti-epileptics in patients with seizures and brain tumours.


Assuntos
Anticonvulsivantes/uso terapêutico , Neoplasias Encefálicas/terapia , Epilepsia/tratamento farmacológico , Glioma/terapia , Neoplasias Encefálicas/complicações , Quimioterapia Combinada , Epilepsia/etiologia , Gabapentina/uso terapêutico , Glioma/complicações , Humanos , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Gradação de Tumores , Fenitoína/uso terapêutico , Taxa de Sobrevida , Topiramato/uso terapêutico , Ácido Valproico/uso terapêutico , Zonisamida/uso terapêutico
14.
JAMA Psychiatry ; 76(4): 374-381, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30865232

RESUMO

Importance: The US Food and Drug Administration recognizes total abstinence and no heavy drinking days as outcomes for pivotal pharmacotherapy trials for alcohol use disorder (AUD). Many patients have difficulty achieving these outcomes, which can discourage seeking treatment and has slowed the development of medications that affect alcohol use. Objective: To compare 2 drinking-reduction outcomes with total abstinence and no heavy drinking outcomes. Design, Setting, and Participants: Data were obtained from 3 multisite, randomized, placebo-controlled clinical trials of medications for treating alcohol dependence (naltrexone, varenicline, and topiramate) in adults with DSM-IV-categorized alcohol dependence. Main Outcomes and Measures: Within each trial, the percentage of participants in active and placebo conditions who met responder definitions of abstinence, no heavy drinking days, a WHO 1-level reduction, and a WHO 2-level reduction was computed by month with corresponding effect sizes (Cohen h). Results: Across the 3 trials (N = 1169; mean [SD] age, 45 [10] years; 824 [70.5%] men), the percentage of participants classified as responders during the last 4 weeks of treatment was lowest for abstinence (naltrexone, 34.7% [100 of 288]; varenicline, 7.3% [7 of 96]; topiramate, 11.7% [21 of 179]) followed by no heavy drinking days (naltrexone, 51.0% [147 of 288]; varenicline, 24.0% [23 of 96]; topiramate, 20.7% [37 of 179]), WHO 2-level reduction (naltrexone, 75.0% [216 of 288]; varenicline, 55.2% [53 of 96]; topiramate, 44.7% [80 of 179]), and WHO 1-level reduction (naltrexone, 83.3% [240 of 288]; varenicline, 69.8 [67 of 96]; topiramate, 54.7% [98 of 179]) outcomes. Standardized treatment effects observed for the WHO 2-level reduction outcomes (naltrexone, Cohen h = 0.214 [95% CI, 0.053 -0.375]; varenicline, 0.273 [95% CI, -0.006 to 0.553]; topiramate, 0.230 [95% CI, 0.024-0.435]) and WHO 1-level reduction (naltrexone, Cohen h = 0.116 [95% CI, -0.046 to 0.277]; varenicline, 0.338 [95% CI, 0.058-0.617]; topiramate, 0.014 [95% CI, -0.192 to 0.219]) were comparable with those obtained using abstinence (naltrexone, Cohen h = 0.142 [95% CI, -0.020 to 0.303]; varenicline, 0.146 [95% CI, -0.133 to 0.426]; topiramate, 0.369 [95% CI, 0.163-0.574]) and no heavy drinking days (naltrexone, Cohen h = 0.140 [95% CI, -0.021 to 0.302]; varenicline, 0.232 [95% CI, -0.048 to 0.511]; topiramate, 0.207 [95% CI, 0.002-0.413]). Conclusions and Relevance: WHO drinking risk level reductions appear to be worthwhile indicators of treatment outcome in AUD pharmacotherapy trials. These outcomes may align with drinking reduction goals of many patients and capture clinically meaningful improvements experienced by more patients than either abstinence or no heavy drinking days. Trial Registration: ClinicalTrials.gov identifiers: NCT00006206; NCT01146613; NCT00210925.


Assuntos
Dissuasores de Álcool/uso terapêutico , Alcoolismo/tratamento farmacológico , Naltrexona/uso terapêutico , Medição de Risco/métodos , Topiramato/uso terapêutico , Vareniclina/uso terapêutico , Adulto , Abstinência de Álcool/estatística & dados numéricos , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Fluids Barriers CNS ; 16(1): 1, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30616618

RESUMO

BACKGROUND: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood-retinal barrier (BRB) and blood-brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II diabetic mice. METHODS: BBB and BRB permeability were assessed using 14C-sucrose and 99mTc-albumin in CD-1 mice fed a low-fat (control) or a high-fat diet. Topiramate administration was compared to saline controls in both preventative and efficacy arms examining BRB and BBB disruption. Body weight and blood glucose were measured weekly and body composition was assessed using EchoMRI. Metabolic activity was measured using a comprehensive laboratory animal monitoring system. Brain tissues collected from the mice were assessed for changes in oxidative stress and tight junction proteins. RESULTS: High-fat feeding caused increased entry of 14C-sucrose and 99mTc-albumin into the brains of diet-induced obese type II diabetic mice. Increased permeability to 14C-sucrose was observed in the hypothalamus and hippocampus, and attenuated by topiramate treatment, while increased permeability to 99mTc-albumin occurred in the whole brain and was also attenuated by topiramate. Treatment with topiramate decreased measures of oxidative stress and increased expression of the tight junction proteins ZO-1 and claudin-12. In the retina, we observed increased entry of 99mTc-albumin simultaneously with increased entry into the whole brain during the preventative arm. This occurred prior to increased entry to the retina for 14C-sucrose which occurred during the efficacy arm. Treatment with topiramate had no effect on the retina. CONCLUSIONS: Blood-brain barrier and blood-retinal barrier dysfunction were examined in a mouse model of diet-induced obese type II diabetes. These studies demonstrate that there are spatial and temporal differences in 14C-sucrose and 99mTc-albumin permeability in the brain and retina of diet-induced obese type II diabetic mice. Topiramate, a mitochondrial carbonic anhydrase inhibitor, is efficacious at both preventing and treating BBB disruption in this diet-induced obese type II diabetic mouse model.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Inibidores da Anidrase Carbônica/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Topiramato/uso terapêutico , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematorretiniana/efeitos dos fármacos , Barreira Hematorretiniana/metabolismo , Permeabilidade Capilar/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2 , Dieta Hiperlipídica/efeitos adversos , Hipocampo/irrigação sanguínea , Hipocampo/metabolismo , Hipotálamo/irrigação sanguínea , Hipotálamo/metabolismo , Masculino , Camundongos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Proteínas de Junções Íntimas/metabolismo
16.
PLoS One ; 14(1): e0210600, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30645607

RESUMO

OBJECTIVE: The aims of this study were to identify the influencing factors such as gender, age, dose and combinations of other antiepileptic drugs (AEDs), especially in triple combinations on the pharmacokinetic of Lamotrigine (LTG) in epilepsy patients of Northwest Chinese Han population. METHODS: Data of the LTG concentration and clinical information were analyzed retrospectively from a therapeutic drug monitoring (TDM) database at the Clinical Pharmacy Laboratory of Xi'an Central Hospital between January 1, 2016 and January 1, 2018. The independent-sample t-test, one-way ANOVA analysis and Bonferroni and Tamhane T3 post-hoc test, the stepwise multivariate regression analysis were adopted by IBM SPSS, version 22.0. RESULTS: 226 serum samples met the inclusion criteria and were evaluated. The mean LTG serum concentration was 5.48±3.83 µg/mL. There were no gender differences (P = 0.64), and there were no significant effects by age on LTG serum concentration after age stratification (3-14 years old, 14-45 years old, 45-59 years old) (P = 0.05). Multiple regression analysis showed that the daily LTG dose and co-administration of other AEDs significantly affected LTG serum concentrations. Combination with enzyme-inducer AEDs, the mean steady-state LTG concentration could be decreased by 30.73% compared with LTG monotherapy. Among enzyme-inducer AEDs, particularly strong inducer Carbamazepine (CBZ) could decrease the mean LTG concentration by 53.65%, but weak inducer AEDs such as Oxcarbazepine (OXC) and Topiramate (TPM) had no effect, Valproic acid (VPA) could increase the mean LTG concentration by 93.95%, and the inducer only partially compensated for the inhibitory effect of VPA in triple combination. CONCLUSIONS: There were no significant gender and age effects, but the LTG daily dose and co-administration of other AEDs significantly affected LTG serum concentration. Combination with enzyme-inducer AEDs, especially CBZ could significantly decrease LTG serum concentrations, VPA could significantly increase LTG serum concentrations, and the inducer only partially compensated for the inhibitory effect of VPA in triple combination. In the clinical setting, these findings can help to estimate LTG concentrations and adjust dosage and evaluate adverse drug reactions.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Lamotrigina/uso terapêutico , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Carbamazepina/uso terapêutico , Criança , Pré-Escolar , China , Quimioterapia Combinada , Epilepsia/etnologia , Feminino , Humanos , Lamotrigina/sangue , Lamotrigina/farmacocinética , Masculino , Pessoa de Meia-Idade , Oxcarbazepina/uso terapêutico , Estudos Retrospectivos , Topiramato/uso terapêutico , Triazinas/uso terapêutico , Ácido Valproico/uso terapêutico , Adulto Jovem
18.
Chin Med J (Engl) ; 132(3): 269-274, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30681492

RESUMO

BACKGROUND: Studies on the relationship between antiepileptic drug (AED) administration and clinical outcomes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) remain scarce. Levetiracetam (LEV) is an AED that is neuroprotective in various neurologic disorders. This study aimed to determine the impact of LEV on the outcome of MELAS. METHODS: A retrospective, single-center study was performed based on a large cohort of patients with MELAS with a history of seizures (n = 102). Decisions on antiepileptic therapies were made empirically. Patients were followed up for 1 to 8 years (median, 4 years) and divided into 2 groups based on whether LEV was administered (LEV or non-LEV). The modified Rankin scale (mRS) scores and mortality risks were analyzed in all patients. RESULTS: LEV, carbamazepine, benzodiazepines, topiramate, oxcarbazepine, valproate, and lamotrigine were administered in 48, 37, 18, 13, 11, 9, and 9 patients, singly or in combination, respectively. The mean mRS score of the LEV group (n = 48) was lower than that of the non-LEV group (n = 54; mean ±â€Šstandard deviation, 2.79 ±â€Š1.47 vs. 3.83 ±â€Š1.93, P = 0.006) up to the end of the study. Nevertheless, there was no difference in the proportion of subjects without disability (mRS ranging 0-1) between the groups (P = 0.37). The multivariate regressions revealed that LEV treatment was associated with lower mRS scores (odds ratio 0.32, 95% confidence interval [CI] 0.15-0.68, P = 0.003) and mortality rates (hazard ratio 0.24, 95% CI 0.08-0.74, P = 0.013). There was a significant difference in the Kaplan-Meier survival curves between the groups (χ = 4.29, P = 0.04). CONCLUSIONS: The LEV administration is associated with lower mortality in patients with MELAS in this retrospective study. Further laboratory research and prospective cohort studies are needed to confirm whether LEV has neuroprotective effects on patients with mitochondrial diseases.


Assuntos
Acidose Láctica/tratamento farmacológico , Acidose Láctica/mortalidade , Anticonvulsivantes/uso terapêutico , Levetiracetam/uso terapêutico , Encefalomiopatias Mitocondriais/tratamento farmacológico , Encefalomiopatias Mitocondriais/mortalidade , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Adolescente , Carbamazepina/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lamotrigina/uso terapêutico , Levetiracetam/administração & dosagem , Masculino , Oxcarbazepina/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Topiramato/uso terapêutico , Ácido Valproico/uso terapêutico
19.
Cochrane Database Syst Rev ; 1: CD010008, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30687937

RESUMO

BACKGROUND: Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate in people with JME. This is an update of a Cochrane Review first published in 2015, and last updated in 2017. OBJECTIVES: To evaluate the efficacy and tolerability of topiramate in the treatment of JME. 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- ), and ClinicalTrials.gov. We also searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted study authors and pharmaceutical companies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) investigating topiramate versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders and proportion of participants experiencing adverse events (AEs). 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 three studies with a total of 83 participants. For efficacy, a greater proportion of participants in the topiramate group had a 50% or more reduction in primarily generalized tonic-clonic seizures (PGTCS) compared with participants in the placebo group. There were no significant differences between topiramate and valproate in participants responding with a 50% or more reduction in myoclonic seizures or in PGTCS, or becoming seizure-free. Concerning tolerability, we ranked AEs associated with topiramate as moderate to severe, while we ranked 59% of AEs linked to valproate as severe complaints. Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group.Overall we judged all three studies to be at high risk of attrition bias and at unclear risk of reporting bias. We judged all three studies to be at low to unclear bias for the remaining risk of bias domains (random sequence, allocation, blinding). We judged the quality of the evidence from the studies to be very low. AUTHORS' CONCLUSIONS: We have found no new studies since the last version of this review was published in 2017. This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but has no clear benefits over valproate in terms of efficacy. Well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Mioclônica Juvenil/tratamento farmacológico , Topiramato/uso terapêutico , Adolescente , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Criança , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Convulsões/tratamento farmacológico , Topiramato/efeitos adversos , Resultado do Tratamento , Ácido Valproico/efeitos adversos , Ácido Valproico/uso terapêutico , Adulto Jovem
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