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1.
N Engl J Med ; 381(22): 2103-2113, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31774955

RESUMO

BACKGROUND: The choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied. METHODS: In a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents - levetiracetam, fosphenytoin, and valproate - in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death. RESULTS: A total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant. CONCLUSIONS: In the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ESETT ClinicalTrials.gov number, NCT01960075.).


Assuntos
Anticonvulsivantes/uso terapêutico , Levetiracetam/uso terapêutico , Fenitoína/análogos & derivados , Estado Epiléptico/tratamento farmacológico , Ácido Valproico/uso terapêutico , Adolescente , Adulto , Anticonvulsivantes/efeitos adversos , Benzodiazepinas/uso terapêutico , Criança , Pré-Escolar , Método Duplo-Cego , Resistência a Medicamentos , Feminino , Humanos , Hipotensão/induzido quimicamente , Infusões Intravenosas , Injeções Intramusculares , Levetiracetam/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fenitoína/efeitos adversos , Fenitoína/uso terapêutico , Ácido Valproico/efeitos adversos , Adulto Jovem
3.
BMJ Case Rep ; 12(7)2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31352389

RESUMO

Fragility fractures are common in older adults and rare in children. Recent studies have demonstrated that hyponatraemia is a novel risk factor for the development of osteoporosis and hip fractures in older people. Animal studies suggest that hyponatraemia can lead to decreased bone mineral density by stimulating osteoclastic activity in order to mobilise sodium from the bone. Reported is a 16-year-old man with intractable epilepsy and an 11-year history of chronic hyponatraemia (126-135 mEq/L) due to valproic acid induced syndrome of inappropriate antidiuresis who sustained low-impact fragility fractures and had evidence of osteopaenia on both X-ray and dual energy X-ray absorptiometry (DEXA). Hyponatraemia resolved following the discontinuation of valproic acid and bone mineral density normalised on a repeat DEXA 19 months later. This case provides evidence supporting the contention that chronic hyponatraemia contributes to osteopaenia and fragility fractures and that the bone abnormalities are potentially reversible following the correction of hyponatraemia.


Assuntos
Anticonvulsivantes/efeitos adversos , Doenças Ósseas Metabólicas/induzido quimicamente , Epilepsia/tratamento farmacológico , Fraturas do Quadril/cirurgia , Hiponatremia/induzido quimicamente , Fraturas por Osteoporose/cirurgia , Ácido Valproico/efeitos adversos , Absorciometria de Fóton , Adolescente , Anticonvulsivantes/uso terapêutico , Densidade Óssea , Fixação Interna de Fraturas , Fraturas do Quadril/diagnóstico por imagem , Humanos , Hiponatremia/complicações , Masculino , Fraturas por Osteoporose/diagnóstico por imagem , Fatores de Risco , Resultado do Tratamento , Ácido Valproico/uso terapêutico
4.
Gen Hosp Psychiatry ; 59: 67-72, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31276904

RESUMO

OBJECTIVE: Valproic acid (VPA)-induced hyperammonemia (VIH), is an increase in blood ammonia levels without any alteration of hepatic enzymes, which can occur during VPA treatment. We aimed to determine the prevalence rate and the risk factors for VIH and its association with cognitive functions. METHOD: A prospective, cross-sectional study was conducted. Patients aged between 18 and 64 who were on VPA treatment and who diagnosed with mood disorders or epilepsy were enrolled in this study (n = 107). For cognitive assessment, Serial 7's and Subjective Memory Complaints Questionnaire (SMCQ) were used. Blood samples were collected for blood VPA and ammonia levels along with other laboratory tests. RESULTS: 55,3% of the sample were considered as VIH. Blood ammonia level significantly correlates with VPA blood levels, total daily dose of VPA and total number of medications concurrently used, but no significant correlation was found between blood ammonia level and cognitive test scores. Gender, body weight, blood VPA levels and the total number of medications concurrently used significantly predicted blood ammonia levels (F(4,81) = 2670, p = 0,038, R2 = 0,116). CONCLUSION: VIH is relatively high in our sample. There is a dose-dependent association between VPA and blood ammonia level. No association was found between cognitive functions and hyperammonemia however with some limitations. Future, prospective cohort studies are needed.


Assuntos
Fármacos do Sistema Nervoso Central/efeitos adversos , Disfunção Cognitiva , Epilepsia , Hiperamonemia , Transtornos do Humor , Ácido Valproico/efeitos adversos , Adolescente , Adulto , Fármacos do Sistema Nervoso Central/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Feminino , Humanos , Hiperamonemia/sangue , Hiperamonemia/induzido quimicamente , Hiperamonemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/epidemiologia , Prevalência , Fatores de Risco , Ácido Valproico/sangue , Adulto Jovem
5.
Rinsho Shinkeigaku ; 59(5): 258-263, 2019 May 28.
Artigo em Japonês | MEDLINE | ID: mdl-31061301

RESUMO

A 79-year-old female was diagnosed with epilepsy because she experienced loss of consciousness twice in January and February and then had a seizure in June 2016. She was treated with 800 mg sodium valproate (sustained release). After 3 days, she experienced loss of appetite, and more than 3 days later, disturbance of consciousness. Serum valproic acid (VPA) concentration was 128.3 µg/ml and serum ammonia was 404 µmol/l. Cerebral edema and status epilepticus occurred. Severe neurological dysfunction remained, even after treatment with continuous hemodiafiltration and levocarnitine. VPA is widely used for the treatment of generalized epilepsy. VPA-induced hyperammonemic encephalopathy is a rare but serious adverse event of VPA. Thus, we must pay attention to serum ammonia levels when using VPA, even VPA monotherapy.


Assuntos
Anticonvulsivantes/efeitos adversos , Cardiomiopatias/induzido quimicamente , Carnitina/deficiência , Epilepsia Generalizada/tratamento farmacológico , Hiperamonemia/induzido quimicamente , Doenças Musculares/induzido quimicamente , Síndromes Neurotóxicas/etiologia , Ácido Valproico/efeitos adversos , Idoso , Amônia/sangue , Anticonvulsivantes/administração & dosagem , Biomarcadores/sangue , Carnitina/administração & dosagem , Transtornos da Consciência/etiologia , Feminino , Humanos , Hiperamonemia/sangue , Hiperamonemia/diagnóstico , Estado Epiléptico/etiologia , Ácido Valproico/administração & dosagem
6.
Expert Opin Pharmacother ; 20(12): 1449-1456, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31099271

RESUMO

Introduction: Sodium valproate is a widely used anti-epileptic drug with a broad spectrum of activity and mechanism of action. It has consequently been the first-line drug for most seizure types in children for the past fifty years. A wide range of side effects come along with these exceptional properties, including teratogenicity and neuro-cognitive impairments in offspring. Therefore, epilepsy treatment in children and adolescents should be reassessed in light of newer antiepileptic drugs as well as a more targeted-approach with older drugs. Areas covered: The authors review the main concerns of valproate use in terms of adverse effects on different systems and drug interactions. The current alternatives to valproate in absence, myoclonic, tonic-clonic and focal onset seizures in children/adolescents are also reviewed. Expert opinion: There are several issues that research should address in antiepileptic therapy and in clinical studies with children, given the peculiarity of this population. Future perspectives in epilepsy therapy should now lead towards an individualized treatment.


Assuntos
Anticonvulsivantes/uso terapêutico , Comportamento de Escolha , Epilepsia/tratamento farmacológico , Ácido Valproico/uso terapêutico , Adolescente , Criança , Epilepsia/epidemiologia , Epilepsia Generalizada/tratamento farmacológico , Humanos , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Convulsões/tratamento farmacológico , Convulsões/epidemiologia , Ácido Valproico/efeitos adversos
7.
Seizure ; 69: 61-69, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30981051

RESUMO

PURPOSE: We systematically reviewed studies to provide current evidence about the incidence and risk of alopecia in patients undergoing valproic acid (VPA) therapy. METHODS: We retrieved relevant publications and gathered data on alopecia in patients taking VPA and other drugs from prospective studies. RESULTS: Twenty-five articles met the inclusion criteria, and the overall incidence of alopecia in patients receiving VPA therapy was 11% (95% confidence interval (CI): 0.08-0.13). The pooled risk of alopecia showed a significant difference between patients treated with VPA and all other drugs (odds ratio (OR) 5.02, 95% CI: 3.58-7.03), other epileptic drugs (AEDs) (OR 4.82, 95% CI: 3.32-7.00) and other non-AEDs (OR 5.84, 95% CI: 2.67-12.81). Compared to other drugs, VPA increased the risk of alopecia both in patients with migraine headaches (OR 6.05, 95% CI: 2.89-12.63) and patients with epilepsy (OR 5.29, 95% CI: 3.53-7.92), and the increase risk was reported more frequently in patients with migraine. Both lower doses (OR 4.38, 95% CI: 2.32-8.25) and shorter treatments (OR 4.98, 95% CI: 2.41-10.25) with VPA posed a high risk of alopecia compared to other drugs, as did higher doses and longer treatment times. CONCLUSIONS: Based on our findings, VPA was significantly associated with a risk of alopecia compared to other drugs, and the risk did not depend on the dose and treatment time.


Assuntos
Alopecia/epidemiologia , Alopecia/etiologia , Epilepsia/tratamento farmacológico , Ácido Valproico/efeitos adversos , Ácido Valproico/uso terapêutico , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Humanos , Incidência , Estudos Prospectivos
8.
Seizure ; 69: 20-24, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30953957

RESUMO

PURPOSE: The aim of the study was to examine the frequency of hyperammonemia secondary to valproic acid treatment in status epilepticus and to describe the characteristics of the patients. METHODS: All patients with established status epilepticus during 2014 to 2016 at Ryhov County Hospital were identified in a retrospective case series. Clinical and laboratory findings were collected from electronic medical files and the Metavision database at the intensive care unit (ICU). Hyperammonemia was defined as a concentration of at least 50 µmol/L. RESULTS: 11 of 40 patients developed hyperammonemia. These patients had a significantly longer stay at the ICU (12.6 vs 2.5 days) and at the hospital (22 vs 11 days). All patients with hyperammonemia were treated at the ICU and all received antibiotics. 12 patients were treated with intravenous valproic acid outside the ICU. Hyperammonemia was not related to Body Mass Index, time to initiation of therapy or laboratory abnormalities except anemia (Hemoglobin 104 vs 122 g/l). There was no difference in mortality between groups. CONCLUSION: The risk of hyperammonemia is almost 40% in patients receiving intravenous valproic acid in the ICU setting. The underlying mechanisms are probably either individual susceptibility or high metabolic demands. A high vigilance should be recommended. These data require further research via prospective designs in which multiple variables are controlled to explore the effects of individual factors on treatment outcome.


Assuntos
Hiperamonemia/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Ácido Valproico/efeitos adversos , Ácido Valproico/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Carnitina/administração & dosagem , Feminino , Humanos , Injeções Intravenosas , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Ácido Valproico/administração & dosagem
10.
Medicine (Baltimore) ; 98(8): e14698, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813219

RESUMO

RATIONALE: The phenotypic spectrum caused by SCN2A mutations includes benign neonatal/infantile seizures, Ohtahara syndrome, infantile spasms, West syndrome, and other unclassified epileptic phenotypes. Mutations in SCN2A have been implicated in neonatal seizure cases. Here, we described a Chinese family with 2 members having juvenile-onset myoclonus and identified a novel SCN2A point mutation within this family. PATIENT CONCERNS: The 21-year-old male proband suffered from frequent myoclonus at 11 years old with subsequent progressive ataxia. His elder maternal half-sister also experienced myoclonus. Genomic DNA of the patients was extracted from the peripheral blood cells of the proband, elder maternal half-sister, parents, and uncle of the proband. Targeted next-generation sequencing was used to screen gene mutations in the proband. The potential functional effects of mutations within SCN2A were predicted In silico analyses. DIAGNOSES: Genetic testing revealed a novel SCN2A variant, c.T4820C, which contains a highly conserved amino acid substitution within segment S5 (p.V1607A). This mutation was predicted to produce a dysfunctional Nav1.2 protein by Mutation Taster and Protein Variation Effect Analyzer (PROVEAN). Genotype-phenotype correlation showed an incomplete penetrance of p.V1607A. INTERVENTIONS: The proband was treated by multiple antiepileptic drugs. These included carbamazepine, oxcarbazepine, valproate, and topiramate. OUTCOMES: The duration of follow up was 2 years, and the proband developed drug-resistant epilepsy. LESSONS: The case gives us the lesson that SCN2A mutation can contribute to juvenile-onset myoclonus. Our findings extend the spectrums of SCN2A mutations and the clinical features of patients with SCN2A mutations.


Assuntos
Carbamazepina , Epilepsia Mioclônica Juvenil , Canal de Sódio Disparado por Voltagem NAV1.2/genética , Adulto , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Ataxia/diagnóstico , Ataxia/etiologia , Carbamazepina/administração & dosagem , Carbamazepina/efeitos adversos , Progressão da Doença , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/genética , Eletroencefalografia/métodos , Feminino , Testes Genéticos/métodos , Humanos , Masculino , Anamnese , Mutação , Epilepsia Mioclônica Juvenil/diagnóstico , Epilepsia Mioclônica Juvenil/tratamento farmacológico , Epilepsia Mioclônica Juvenil/genética , Exame Neurológico/métodos , Oxcarbazepina/administração & dosagem , Oxcarbazepina/efeitos adversos , Linhagem , Ácido Valproico/administração & dosagem , Ácido Valproico/efeitos adversos
11.
Int J Hematol ; 109(6): 694-699, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30915718

RESUMO

Anticonvulsant administration is the standard of care for prevention of busulfan-induced seizures (BIS) in hematopoietic stem cell transplantation (HSCT). While valproate interacts with other drugs, including carbapenem antibiotics, levetiracetam has no known clinically significant interactions. Only a few reports have discussed the use of levetiracetam for the prevention of BIS in HSCT recipients. This retrospective study aimed to evaluate the efficacy and safety of valproate and levetiracetam for BIS prophylaxis in adult HSCT recipients. We identified patients who received valproate or levetiracetam to prevent BIS at the National Cancer Center Hospital from December 2015 to November 2017. Ninety-one patients were analyzed (valproate group 45; levetiracetam group 46). No BIS occurred in either group. The pattern of anticonvulsant-related adverse events was similar in both groups, except for a higher incidence of rash in the valproate group. Carbapenem antibiotics were more frequently used in the levetiracetam group than in the valproate group. In conclusion, valproate and levetiracetam are effective and safe for the prophylaxis of BIS. Levetiracetam may be more useful in patients colonized with extended-spectrum beta-lactamase-producing bacteria due to its lack of any clinically significant drug-drug interactions.


Assuntos
Anticonvulsivantes/administração & dosagem , Bussulfano/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/efeitos adversos , Levetiracetam/administração & dosagem , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Ácido Valproico/administração & dosagem , Adulto , Idoso , Anticonvulsivantes/efeitos adversos , Feminino , Humanos , Levetiracetam/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ácido Valproico/efeitos adversos , Adulto Jovem
12.
Epilepsy Res ; 153: 7-13, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30925397

RESUMO

BACKGROUND AND AIMS: The relationship between anti-epileptic usage and oxidative damage has not yet been clearly understood. In our study, we investigated oxidative stress parameters, carnitine levels, liver function tests (LFT) and their relationship in epileptic children treated with valproic acid or levetiracetam. METHOD: LFTs, serum free carnitine and oxidative damage markers and their relations with each other were determined in patients who are on valproic acid or levetiracetam treatment at least for 6 months. 25 patients on therapeutic doses of valproic acid, 26 patients on therapeutic doses of levetiracetam and 26 healthy volunteers as controls were included. LFTs, ammonia, carnitine, lipid peroxidation biomarker malondialdehyde (MDA) and a sensitive marker of DNA damage, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were measured. Results of patients are compared to healthy controls. The data is evaluated with IBM SPSS Statistics 22.0. RESULTS: Ammonia and MDA levels were elevated in patients using levetiracetam; 8-OHdG levels were elevated in both patient groups. Carnitine levels were significantly low in patients under valproic acid therapy, however they were not found to be correlated with MDA, 8-OHdG or LFTs. MDA showed positive correlation with ammonia and 8-OHdG in the levetiracetam group. CONCLUSION: We did not observe hepatotoxicity in patients under therapeutic doses of valproic acid. However, epileptic children under therapeutic doses of levetiracetam showed significantly elevated levels of MDA and 8-OHdG, which is supportive for oxidative damage under levetiracetam therapy. This result was observed for the first time in childhood epilepsies and further studies are needed to understand its mechanism.


Assuntos
Carnitina/sangue , Epilepsia/tratamento farmacológico , Levetiracetam/efeitos adversos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Ácido Valproico/efeitos adversos , Anticonvulsivantes , Criança , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Epilepsia/sangue , Feminino , Humanos , Testes de Função Hepática , Masculino , Malondialdeído/metabolismo , Estudos Retrospectivos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
13.
J Zhejiang Univ Sci B ; 20(3): 253-263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30829012

RESUMO

Valproic acid (VPA), an agent that is used to treat epileptic seizures, can cause spatial memory impairment in adults and children. This effect is thought to be due to the ability of VPA to inhibit neurogenesis in the hippocampus, which is required for learning. We have previously used an animal model to show that VPA significantly impairs hippocampal-spatial working memory and inhibits neuronal generation in the sub-granular zone of the dentate gyrus. As there are patient reports of improvements in memory after discontinuing VPA treatment, the present study investigated the recovery of both spatial memory and hippocampal neurogenesis at two time points after withdrawal of VPA. Male Wistar rats were given intraperitoneal injections of 0.9% normal saline or VPA (300 mg/kg) twice a day for 10 d. At 1, 30, or 45 d after the drug treatment, the novel object location (NOL) test was used to examine spatial memory; hippocampal cell division was counted using Ki67 immunohistochemistry, and levels of brain-derived neurotrophic factor (BDNF) and Notch1 were measured using western immunoblotting. Spatial working memory was impaired 1 and 30 d after the final administration, but was restored to control levels by 45 d. Cell proliferation had increased to control levels at 30 and 45 d. Both markers of neurogenesis (BDNF and Notch1 levels) had returned to control levels at 45 d. These results demonstrate that memory recovery occurs over a period of six weeks after discontinuing VPA treatment and is preceded by a return of hippocampal neurogenesis to control levels.


Assuntos
Hipocampo/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Ácido Valproico/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proliferação de Células , Cognição/efeitos dos fármacos , Giro Denteado/efeitos dos fármacos , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacologia , Hipocampo/metabolismo , Imuno-Histoquímica , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/terapia , Neurônios/metabolismo , Ratos , Ratos Wistar , Receptor Notch1/metabolismo , Memória Espacial/efeitos dos fármacos , Ácido Valproico/efeitos adversos
14.
Cochrane Database Syst Rev ; 2: CD003032, 2019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30734919

RESUMO

BACKGROUND: This is an updated version of the Cochrane Review previously published in 2017.Absence seizures (AS) are brief epileptic seizures which present in childhood and adolescence. Depending on clinical features and electroencephalogram (EEG) findings they are divided into typical, atypical absences, and absences with special features. Typical absences are characterised by sudden loss of awareness and an EEG typically shows generalised spike wave discharges at three cycles per second. Ethosuximide, valproate and lamotrigine are currently used to treat absence seizures. This review aims to determine the best choice of antiepileptic drug for children and adolescents with AS. OBJECTIVES: To review the evidence for the effects of ethosuximide, valproate and lamotrigine as treatments for children and adolescents with absence seizures (AS), when compared with placebo or each other. SEARCH METHODS: For the latest update we searched the Cochrane Register of Studies (CRS Web, 29 May 2018), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 29 May 2018), ClinicalTrials.gov (29 May 2018) and the WHO International Clinical Trials Registry Platform (ICTRP, 29 May 2018). Previously we searched Embase (1988 to March 2005) and SCOPUS (1823 to 31 March 2014), but this is no longer necessary because randomised controlled trials (RCTs) and quasi-RCTs in Embase and SCOPUS are now included in CENTRAL. No language restrictions were imposed. In addition, we contacted Sanofi Winthrop, Glaxo Wellcome (now GlaxoSmithKline) and Parke Davis (now Pfizer), manufacturers of sodium valproate, lamotrigine and ethosuximide respectively. SELECTION CRITERIA: Randomised parallel group monotherapy or add-on trials which include a comparison of any of the following in children or adolescents with AS: ethosuximide, sodium valproate, lamotrigine, or placebo. DATA COLLECTION AND ANALYSIS: Outcome measures were: (1) proportion of individuals seizure free at one, three, six, 12 and 18 months post randomisation; (2) people with a 50% or greater reduction in seizure frequency; (3) normalisation of EEG and/or negative hyperventilation test; and (4) adverse effects. Data were independently extracted by two review authors. Results are presented as risk ratios (RR) with 95% confidence intervals (95% CIs). We used GRADE quality assessment criteria to evaluate the certainty of evidence derived from all included studies. MAIN RESULTS: On the basis of our selection criteria, we included no new studies in the present review. Eight small trials (total number of participants: 691) were included from the earlier review. Six of them were of poor methodological quality (unclear or high risk of bias) and seven recruited less than 50 participants. There are no placebo-controlled trials for ethosuximide or valproate, and hence, no evidence from RCTs to support a specific effect on AS for either of these two drugs. Due to the differing methodologies used in the trials comparing ethosuximide, lamotrigine and valproate, we thought it inappropriate to undertake a meta-analysis. One large randomised, parallel double-blind controlled trial comparing ethosuximide, lamotrigine and sodium valproate in 453 children with newly diagnosed childhood absence epilepsy found that at 12 months, the freedom-from-failure rates for ethosuximide and valproic acid were similar and were higher than the rate for lamotrigine. The frequency of treatment failures due to lack of seizure control (P < 0.001) and intolerable adverse events (P < 0.037) was significantly different among the treatment groups, with the largest proportion of lack of seizure control in the lamotrigine cohort, and the largest proportion of adverse events in the valproic acid group. Overall, this large study demonstrates the superior effectiveness of ethosuximide and valproic acid compared to lamotrigine as initial monotherapy aimed to control seizures without intolerable adverse effects in children with childhood absence epilepsy. The risk of bias for this study was low. We rated the overall certainty of the evidence available from the included studies to be moderate or high. AUTHORS' CONCLUSIONS: Since the last version of this review was published, we have found no new studies. Hence, the conclusions remain the same as the previous update. With regards to both efficacy and tolerability, ethosuximide represents the optimal initial empirical monotherapy for children and adolescents with AS. However, if absence and generalised tonic-clonic seizures coexist, valproate should be preferred, as ethosuximide is probably inefficacious on tonic-clonic seizures.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Tipo Ausência/tratamento farmacológico , Etossuximida/uso terapêutico , Lamotrigina/uso terapêutico , Ácido Valproico/uso terapêutico , Adolescente , Anticonvulsivantes/efeitos adversos , Criança , Etossuximida/efeitos adversos , Humanos , Lamotrigina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Valproico/efeitos adversos
16.
J Affect Disord ; 245: 812-818, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30699864

RESUMO

BACKGROUND: Divalproex has become the most prevalent mood stabilizer for bipolar disorder. However, little is known its effects in the prevention of suicide in patients with bipolar disorder, and recent FDA announcement indicated an increased risk of suicidality when using anti-epileptic agents such as divalproex. The aim of this study is to investigate the effect of divalproex on suicide risk in patients with bipolar disorder. METHODS: A search strategy was used for the PubMed, Embase, ProQuest, ScienceDirect, Cochrane Library, ClinicalKey, Web of Science, and ClinicalTrials.gov until June 13th, 2018. Peer-reviewed observationally clinical studies in humans, investigating the association of divalproex and suicidality in patients with bipolar disorder were included. A random-effects meta-analysis was implemented to calculate the relative risk (RR) and 95% confidence intervals (CIs) for suicidality among patients receiving divalproex and those without. RESULTS: Total 6 studies were included in the final meta-analysis. There was no significant difference in the incidence rates (reported as [RR]; 95% CI) of suicide attempts (0.921; 0.383-2.215) or completed suicides (0.607; 0.180-2.043) between participants receiving divalproex vs. no medication. There was no significant difference in the incidence rates of suicide attempts (0.815; 0.453-1.466) or completed suicides (1.009; 0.410-2.484) between participants receiving divalproex and carbamazepine. LIMITATIONS: The significantly heterogeneous sample sources and study design amount the included trials. CONCLUSIONS: Treatment with divalproex did not reduce or increase the incidence of suicide-related events in patients with bipolar disorder.


Assuntos
Antimaníacos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Internacionalidade , Estudos Observacionais como Assunto , Tentativa de Suicídio/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Ácido Valproico/efeitos adversos , Antimaníacos/uso terapêutico , Humanos , Ácido Valproico/uso terapêutico
17.
Australas Psychiatry ; 27(2): 125-128, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30763123

RESUMO

OBJECTIVES: To describe prescription of sodium valproate (SV) for bipolar mood disorder to potentially child-bearing women within one public mental health service and describe risks of fetal exposure, and safe prescribing practices among psychiatrists. METHODS: A 24-month retrospective chart review with descriptive analysis; narrative review of literature and guidelines. RESULTS: Review of 383 charts demonstrated prescription of valproate to 20% of 98 women aged 15-45, with little evidence of advice regarding risk and contraception. Robust evidence of teratogenic and neurodevelopmental risk underpins increased regulation, and recommendations that valproate not be prescribed to this cohort. CONCLUSIONS: The significant risks associated with SV oblige all prescribers to proactively access authoritative guidelines such as those published by the Centre of Perinatal Excellence.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Padrões de Prática Médica , Complicações na Gravidez/tratamento farmacológico , Teratogênios , Ácido Valproico/uso terapêutico , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Antimaníacos/efeitos adversos , Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Epilepsia/tratamento farmacológico , Feminino , Humanos , Gravidez , Complicações na Gravidez/psicologia , Fatores de Risco , Ácido Valproico/efeitos adversos
19.
Seizure ; 66: 70-75, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30807902

RESUMO

PURPOSE: Tremor is frequently observed in patients with epilepsy (PWE), which is generally attributed to the side-effect of antiepileptic drugs (AEDs) particularly valproate (VPA) with largely unknown mechanisms. The study aimed to assess the clinical features and related factors of tremor in PWE with tremor. METHODS: PWE with tremor and a control group of age- and sex-matched PWE without tremor were enrolled. Detailed demographic and clinical information for each individual was recorded. PWE with tremor were evaluated by The Clinical Rating Scale for Tremor (CRST) and Tremor Related Activities of Daily Living (TRADL) questionnaire. RESULTS: 132 individuals were enrolled, which including sixty-six (36 males) PWE with tremor with mean age of 33 years and epilepsy duration of 12.5 years. Tremor was postural in all, with median duration of four and one year from diagnosis and AED treatment to the onset of tremor respectively. The upper limbs were predominantly affected. VPA had been used in 62 (93.9%) PWE with tremor compared to 31 (47.0%) PWE without tremor (P < 0.001). The total CRST score was significantly associated with epilepsy duration and maximum VPA dosage (B = 0.30, p < 0.001; B = 0.32, p = 0.013). Patients with VPA dosage over 17.05 mg/kg/d might be more vulnerable to develop tremor. CONCLUSIONS: PWE with tremor were more frequently treated with VPA, however, tremor was mild in most without any functional impairment. Epilepsy duration and maximum VPA dosage were important factors of tremor severity, suggesting mechanisms underlying tremor in PWE may be an elaborate interplay of AEDs and disease itself.


Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia/complicações , Tremor/etiologia , Atividades Cotidianas , Adulto , Anticonvulsivantes/uso terapêutico , Estudos de Casos e Controles , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Epilepsia/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inquéritos e Questionários , Tremor/psicologia , Extremidade Superior/fisiopatologia , Ácido Valproico/efeitos adversos , Adulto Jovem
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