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1.
Expert Opin Pharmacother ; 21(3): 253-260, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31957501

RESUMO

Introduction: Lurasidone has been approved in the United States as a monotherapy and adjunct for acute bipolar I depression, as well as an antipsychotic for patients with schizophrenia.Areas covered: Herein, the authors review the pharmacodynamics and pharmacokinetics of lurasidone as well and the major randomized clinical trials. The authors also provide their expert opinion.Expert opinion: Lurasidone has not been studied in patients with mania or bipolar psychosis. It has been studied, both as a monotherapy and adjunctive treatment to lithium or valproate, in acute depression and in prevention of recurrence of any mood episode in patients with bipolar disorder initially treated for bipolar depression or mania. It is approved in the United States for acute bipolar I depression. It has clinically meaningful treatment effect sizes for improvement in depression compared to placebo (0.51 monotherapy, 0.34 adjunct). The number needed to treat (NNT) for response with monotherapy was 5 (for both lower and higher dose groups), and for remission was 6 and 7 (for lower dose and higher dose groups, respectively); the NNT for adjunctive therapy was 7. It has not demonstrated efficacy in relapse prevention when added to a mood stabilizer but is safe in combination with other medications.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Cloridrato de Lurasidona/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Ácido Valproico/uso terapêutico
2.
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.
Medicina (B Aires) ; 79 Suppl 3: 6-9, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31603835

RESUMO

The objective was to describe the frequency, mode of presentation and characteristics of epilepsy in children with congenital hemiparesis (CH). It is a etrospective, descriptive and multicenter study, based on the collection of data from the clinical records of patients from 0 to 19 years with CH secondary to perinatal infarction in different centers of the community of Catalonia. A total of 310 children were included (55% males and 45% females), from a total of 13 centers in Catalonia. Average age of onset of the crises was 2 ± 1 year. Epilepsy was present in 29.5% (n = 76), among which the most frequent vascular subtype was arterial presumed perinatal ischemic stroke (51.3%), followed by neonatal arterial ischemic stroke (18.4%), periventricular venous infarction (15.8%), neonatal hemorrhagic stroke (10.5%) and neonatal cerebral sinovenous thrombosis (3.9%). Semiology of the most frequent seizures was motor focal in 82%, followed by focal motor with secondary bilateralization in 23%, focal discognitive in 13.5%, generalized by 2% and spasms in 6.5%. The 67.3% were controlled with monotherapy and the drugs used were valproate, levetiracetam or carbamazepine. The antecedent of electrical status during sleep was identified in 3 patients, all associated with extensive lesions that included the thalamus. Of the total number of children with epilepsy, 35% began with neonatal seizu res in the first 3 days of life. The 30% of children with perinatal stroke and CH present a risk of epilepsy during childhood. Children with ischemic strock have the highest risk, so they will require a follow-up aimed at detecting prematurely the epilepsy and start a treatment.


Assuntos
Epilepsia/etiologia , Paresia/congênito , Paresia/etiologia , Acidente Vascular Cerebral/complicações , Adolescente , Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Criança , Pré-Escolar , Epilepsia/tratamento farmacológico , Feminino , Humanos , Lactente , Recém-Nascido , Levetiracetam/uso terapêutico , Masculino , Estudos Retrospectivos , Fatores de Risco , Convulsões/etiologia , Espanha , Ácido Valproico/uso terapêutico , Adulto Jovem
4.
Horm Metab Res ; 51(8): 511-521, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31408897

RESUMO

We conducted this meta-analysis to evaluate effects of second-generation anti-epileptic drugs (AEDs; levetiracetam, lamotrigine) compared to first-generation AEDs (valproic acid, carbamazepine) on bone metabolism in epilepsy patients. PubMed, Web of Science, Clinical trials.gov, Wanfang, and China national knowledge infrastructure databases were searched. Ten trials were included. Results showed: (1) The overall SMD for changes of serum calcium, phosphorus, ALP, and PTH levels from baseline of LEV versus first-generation AEDs were 1.00 (95% CI=0.23-1.77, Z=2.56, p=0.01), 0.98 (95% CI=- 0.05 to 2.01, Z=1.86, p=0.06), - 1.17 (95% CI=- 2.08 to - 0.25, Z=2.50, p=0.01), 0.07 (95% CI=- 0.14 to 0.27, Z=0.63, p=0.53), respectively. (2) The overall SMD for changes of serum calcium, phosphorus, ALP, and PTH levels from baseline of LTG versus first-generation AEDs were -0.16 (95% CI=- 0.47 to 0.16, Z=0.99, p=0.32), -0.05 (95% CI=- 0.55 to 0.44, Z=0.22, p=0.83), 0.10 (95% CI=- 0.53 to 0.73, Z=0.31, p=0.75), -0.05 (95% CI=- 0.52 to 0.42, Z=0.22, p=0.83), respectively. Overall, our results indicate that compared to first-generation AEDs, LEV has less adverse effects on blood bone metabolism markers in epilepsy patients, while LTG does not. However, due to small number of included studies, our results warrant additional research.


Assuntos
Anticonvulsivantes/uso terapêutico , Osso e Ossos/metabolismo , Carbamazepina/uso terapêutico , Epilepsia/tratamento farmacológico , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Ácido Valproico/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Ensaios Clínicos como Assunto , Humanos , Prognóstico
5.
Expert Opin Pharmacother ; 20(17): 2115-2120, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31446808

RESUMO

Introduction: Atypical absences are generalized epileptic seizures typically affecting children with severe epilepsies and learning difficulties along with other seizure types. Video-EEG is essential for their diagnosis. Recently, atypical absence seizures have been reported as a hallmark of some developmental and epileptic encephalopathies.Areas covered: This is a narrative review of the literature which describes the electroclinical features of atypical seizures, the characteristics of developmental epileptic encephalopathies in which this seizure type can occur, and the evidence supporting the use of individual antiseizure drugs for the treatment of atypical absences.Expert opinion: Treatment of absence seizures typically relies on ethosuximide (ineffective against tonic-clonic seizures), valproate (associated with larger proportion of adverse events), or lamotrigine (less effective than the other two). However, unlike typical absences, atypical absences are usually intractable, persist lifetime, and their prognosis depends on the underlying etiology or associated epilepsy syndrome. Besides efficacy, other relevant factors, such as drug formulation, ease of titration and dosing, and drug interactions, should be considered. Drugs that may worsen epilepsy, cognition and behavior should be avoided. In the vast majority of patients, a polytherapy is required, although usually with limited efficacy. Finally, epilepsy syndromes featuring atypical absences require a multidisciplinary approach.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Generalizada/tratamento farmacológico , Etossuximida/uso terapêutico , Humanos , Lamotrigina/uso terapêutico , Síndrome de Lennox Gastaut/tratamento farmacológico , Síndrome de Lennox Gastaut/patologia , Ácido Valproico/uso terapêutico , Proteínas Ativadoras de ras GTPase/genética , Proteínas Ativadoras de ras GTPase/metabolismo
6.
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
7.
Dan Med J ; 66(8)2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31315793

RESUMO

INTRODUCTION: We studied the use of antiepileptic drugs (AEDs) in women of fertile age and pregnant women in a 16-year-period in Denmark. METHODS: We included all women of fertile age (age 18-44 years) and pregnant women from 2001 to 2016 identified from Danish registers. RESULTS: The median proportion of women of fertile age who took AEDs increased from 10.7‰ (95% confidence interval (CI): 10.5-10.9‰) in 2001 to 27.1‰ (95% CI: 26.8-27.4‰) in 2016. Lamotrigine, levetiracetam, gabapentin and pregabalin have been increasingly used over time and have been the main AEDs used in recent years. The use of valproate in women of fertile age decreased slightly from 2.1‰ (95% CI: 2.0-2.2‰) to 1.9‰ (95% CI: 1.8-2.0‰), which was explained by a decrease in the use after 2014 among women aged 18-24 years. The increased use of AEDs was likely owed to use for other indications than epilepsy. The overall use of AEDs in pregnant women increased from 3.8‰ (95% CI: 3.3-4.3‰) in 2001 to 6.9‰ (95% CI: 6.2-7.6‰) in 2016, and the use of valproate decreased from 0.6‰ (95% CI: 0.4-0.8‰) in 2001 to 0.2‰ (95% CI: 0.1-0.4‰) in 2016. CONCLUSIONS: The overall use of AEDs in women of fertile age and pregnant women has increased in the past 16 years, especially due to an increased use of lamotrigine. However, valproate use in pregnant women and in younger women of fertile age has become less frequent. FUNDING: This study received funding from the Lundbeck Foundation, the Danish Epilepsy Association, the Central Denmark Region and the Novo Nordisk Foundation (NNF16OC0019126). TRIAL REGISTRATION: none.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Adolescente , Adulto , Dinamarca , Feminino , Gabapentina , Humanos , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Gravidez , Resultado da Gravidez/epidemiologia , Ácido Valproico/uso terapêutico , Adulto Jovem
8.
Seizure ; 70: 77-81, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31310965

RESUMO

PURPOSE: To evaluate the change in the number of female valproate users in Lithuania from 2013 to 2018 and determine the presumed impact of two distinct European Medicines Agency (EMA) regulatory interventions on the observed trend. METHOD: An interrupted time series analysis was performed using reimbursement data from the National Health Register Fund to detect changes in user trends after a selected regulatory event in time. RESULTS: The absolute number of female patients under 50 using valproate is seen decreasing over time. After an EMA regulatory procedure in 2014, there was only a delayed decrease in female valproate users under 15 (a change in trend of -4.83, 95%CI = -9.45 to -0.22, P = 0.041, a decrease in level 15 months post-intervention of -40.06, 95%CI = -79.26 to -0.86, P = 0.046). An increase in new prescriptions for patients with epilepsy was noted post-intervention (change in trend 13.75, 95%CI = 6.03-21.48, P = 0.004). The EMA referral procedure in 2017-2018 was followed by a lasting decrease in female valproate users of reproductive age and older (level effect 3 months post-intervention: -201.28, 95%CI = -310.61 to -91.96, P = 0.001 and -170.60, 95%CI = -287.73 to -53.48, P = 0.007, respectively). However, the rate of new initiations on valproate for patients with either epilepsy or mood disorders remained constant. CONCLUSIONS: The number of female patients under 50 using valproate is decreasing over time. The 2018 EMA referral procedure was followed by a notable reduction in female valproate users.


Assuntos
Anticonvulsivantes/uso terapêutico , Uso de Medicamentos/tendências , Ácido Valproico/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Lituânia , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Adulto Jovem
9.
Med Sci Monit ; 25: 4627-4638, 2019 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-31266934

RESUMO

BACKGROUND Subclinical epileptiform discharges (SEDs) are defined as epileptiform electroencephalographic (EEG) discharges without clinical signs of seizure in patients. The subthreshold convulsant discharge (SCD) is a frequently used model for SEDs. This study aimed to investigate the effect of levetiracetam (LEV), an anti-convulsant drug, on cognitive impairment of SCD model rats and to assess the associated mechanisms. MATERIAL AND METHODS A SCD rat model was established. Rats were divided into an SCD group, an SCD+ sodium valproate (VPA) group, and an SCD+ levetiracetam (LEV) group. The Morris water maze was used to evaluate the capacity of positioning navigation and space exploration. The field excitatory post-synaptic potentials (fEPSPs) were evaluated using a bipolar stimulation electrode. NCAM, GAP43, PS95, and CaMK II levels were detected using Western blot and RT-PCR, respectively. PKC activity was examined by a non-radioactive method. RESULTS LEV shortens the latency of platform seeking in SCD rats in positioning navigation. fEPSP slopes were significantly lower in the SCD group, and LEV treatment significantly enhanced the fEPSP slopes compared to the SCD group (P<0.05). The NCAM and GAP-43 levels were increased and PSD-95 levels were increased in SCD rats (P<0.05), which were improved by LEV treatment. The PKC activity and CaMK II levels were decreased in SCD rats and LEV treatment significantly enhanced PKC activity and increased CaMK II levels. CONCLUSIONS Cognitive impairment in of SCD model rats may be caused by decreased PKC activity, low expression of CaMK II, and inhibition of LTP formation. LEV can improve cognitive function by activating the PKC-GAP-43-CaMK signal transduction pathway.


Assuntos
Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/prevenção & controle , Levetiracetam/farmacologia , Animais , Proteínas Quinases Dependentes de Cálcio-Calmodulina/efeitos dos fármacos , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de Doenças , Eletroencefalografia , Proteína GAP-43/efeitos dos fármacos , Proteína GAP-43/metabolismo , Hipocampo/metabolismo , Levetiracetam/metabolismo , Masculino , Fosforilação , Proteína Quinase C/efeitos dos fármacos , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-Dawley , Convulsões/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Ácido Valproico/uso terapêutico
10.
BMC Neurol ; 19(1): 166, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315588

RESUMO

BACKGROUND: Acquired epileptiform opercular syndrome (AEOS) with electrical status epilepticus during sleep (ESES) may be recurrent and intractable. The real-time transcranial Doppler ultrasound-sleep-deprived video electroencephalogram (TCD-SDvEEG) can be used to observe the relationships among hemodynamic, electrophysiological, and clinical factors in a patient during therapy. This study reported the case of a healthy 5-year-old boy with AEOS. CASE PRESENTATION: The patient had initial seizures during sleep at the age of 1 year, with the left mouth pouting, left eye blinking and drooling for several seconds, and, sometimes, the left upper-limb flexion and head version to the left, lasting for 1-2 min. The combined antiepileptic drug regimens, including valproate, lamotrigine, and clonazepam, failed in the present case. Therefore, the add-on high-dose methylprednisolone therapy was provided. Also, the serial TCD-SDvEEG was used to monitor the dynamic changes before and after add-on steroid treatment. The results showed less than 15% variation in the range of blood flow fluctuation with spikes during non-rapid eye movement sleep after treatment. This was similar to the outcomes in healthy children and also accorded with the clinical improvements such as seizure control, drooling control, and language ability melioration. However, 95% of spike-wave index (SWI) was still maintained. The improvements in cerebral hemodynamics and clinical manifestations were faster and earlier than the SWI progression. CONCLUSIONS: The real-time TCD-SDvEEG was highly sensitive in detecting therapeutic changes. The findings might facilitate the understanding of the mechanisms underlying neurovascular coupling in patients with AEOS accompanied by ESES.


Assuntos
Eletroencefalografia/métodos , Transtornos do Sono-Vigília/diagnóstico , Estado Epiléptico/diagnóstico , Anticonvulsivantes/uso terapêutico , Pré-Escolar , Humanos , Masculino , Metilprednisolona/uso terapêutico , Convulsões/tratamento farmacológico , Sono/fisiologia , Transtornos do Sono-Vigília/fisiopatologia , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/fisiopatologia , Síndrome , Falha de Tratamento , Ultrassonografia Doppler Transcraniana , Ácido Valproico/uso terapêutico
11.
Seizure ; 70: 71-76, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31302303

RESUMO

PURPOSE: After a huge campaign of information on the teratogenic risk of sodium valproate (VPA) having taken place in France we aimed to evaluate the trend of its prescriptions in young epileptic girls. METHOD: Using the French National Health Insurance Database we searched for patients aged 0-14 years being supplied an antiepileptic drug (AED) between 2010 and 2016. RESULTS: 113,362 children received at least one AED, 61,259 boys and 52,103 girls. Compared to 2010-2014 years, VPA was less prescribed in 2016 as first AED (29% vs 37.3% respectively). The difference between the two periods was greater for girls (-41%) than for boys (-12%). CONCLUSION: The changing trend of VPA as first AED prescribed, particularly in girls, reflects published evidence in terms of safety.


Assuntos
Anticonvulsivantes/uso terapêutico , Ácido Valproico/uso terapêutico , Adolescente , Criança , Pré-Escolar , Prescrições de Medicamentos , Feminino , França/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Programas Nacionais de Saúde , Padrões de Prática Médica/tendências , Teratogênios
12.
Cochrane Database Syst Rev ; 6: CD004048, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31152444

RESUMO

BACKGROUND: Bipolar disorder is a common condition associated with high morbidity; developing efficacious, safe treatments is therefore essential. Lithium is an effective maintenance treatment for bipolar disorder. It acts as mood stabiliser and reduces the risk of suicide. However, evidence assessing the efficacy of lithium in the treatment of acute mania is less robust. Current evidence-based guidelines cite multiple anti-dopaminergic and mood-stabilising agents as initial treatments: more definite evidence is needed to decide if lithium should be the first-line therapy. OBJECTIVES: 1. To assess the effects of lithium in comparison with placebo or other active treatment in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder.2. To review the acceptability and tolerability of treatment with lithium in comparison with placebo or other active treatments in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase, and PsycINFO. We also searched the World Health Organization trials portal (ICTRP) and ClinicalTrials.gov. We checked the reference lists of all included studies and relevant systematic reviews. We have incorporated studies from searches to 18 May 2018 into the current analyses. SELECTION CRITERIA: Prospective randomised controlled studies comparing lithium with placebo or alternative drug treatment in treatment of acute mania. We included anyone with bipolar disorder, male and female, of any age. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data and assessed methodological quality. We used odds ratios (ORs) to analyse binary efficacy outcomes, and mean differences (MDs) or standardised mean differences (SMDs) for continuously distributed outcomes. We used a fixed-effect model unless heterogeneity was moderate or substantial, in which case we used a random-effects model. We used Review Manager 5 to analyse data. We assessed the certainty of evidence for individual outcomes using the GRADE approach. MAIN RESULTS: We found 36 randomised controlled studies comparing lithium with placebo, one of 12 drugs, or electroconvulsive therapy for treatment of acute mania. Studies included male and female participants (n = 4220), of all ages, who all fitted criteria for a manic episode within the context of a diagnosis of bipolar disorder.Risk of bias was variable; 12 studies had a high risk of bias in one domain and 27 gave inadequate information on randomisation leading to an 'unclear' rating for selection bias.Lithium versus placeboHigh-certainty evidence found that lithium was an effective treatment for acute mania and was more effective than placebo at inducing a response (OR 2.13, 95% confidence interval (CI) 1.73 to 2.63; participants = 1707; studies = 6; I2 = 16%; high-certainty evidence), or remission (OR 2.16, 95% CI 1.73 to 2.69; participants = 1597; studies = 5; I2 = 21%; high-certainty evidence).Lithium was more likely than placebo to cause tremor (OR 3.25, 95% CI 2.10 to 5.04; participants = 1241; studies = 6; I2 = 0%; high-certainty evidence), and somnolence (OR 2.28, 95% CI 1.46 to 3.58; participants = 1351; studies = 7; I2 = 0%; high-certainty evidence).There was insufficient evidence to determine the effect of lithium for all-cause dropouts (OR 0.76; 95% CI 0.46 to 1.25; participants = 1353; studies = 7; I2 = 75%; moderate-certainty evidence), and weight gain (OR 1.48, 95% CI 0.56 to 3.92; participants = 735, studies = 3; I2= 51%; moderate-certainty evidence).Lithium versus antipsychotics or mood stabilisersFor the outcome of inducing a response, there was only very low-certainty evidence regarding lithium compared to haloperidol (MD -2.40, 95% CI -6.31 to 1.50; participants = 80; studies = 3; I2 = 95%), quetiapine (OR 0.66, 95% CI 0.28 to 1.55; participants = 335; studies = 2; I2 = 71%), and carbamazepine (SMD 0.21, 95% CI -0.18 to 0.60; participants = 102; studies = 3; I2 = 0%).Lithium was probably less likely to induce a response than olanzapine (OR 0.44, 95% CI 0.20 to 0.94; participants = 180; studies = 2; I2 = 0%; moderate-certainty evidence).Lithium may be less likely to induce a response than risperidone (MD 7.28, 95% CI 5.22 to 9.34; participants = 241; studies = 3; I2 = 49%; low-certainty evidence).There was no evidence of a difference between lithium and valproate (OR 1.22, 95% CI 0.87 to 1.70; participants = 607; studies = 5; I2 = 22%; moderate-certainty evidence).There was moderate-certainty evidence that lithium was more effective than topiramate at treating acute mania (OR 2.28, 95% CI 1.63 to 3.20; participants = 660; studies = 1).Data on adverse events for these comparisons contained too few studies to provide high-certainty evidence. AUTHORS' CONCLUSIONS: This systematic review indicates that lithium is more effective than placebo as a treatment for acute mania but increases the risk for somnolence and tremor. Limited evidence suggests little or no difference between lithium and other mood stabilisers (valproate, carbamazepine) or antipsychotics (risperidone, quetiapine, haloperidol). Olanzapine may be an exception, as it is probably slightly more effective than lithium. There is uncertain evidence that risperidone may also be more effective than lithium. Lithium is probably more effective at treating acute mania than topiramate. When compared to placebo, lithium was more likely to cause adverse events. However, when compared to other drugs, too few studies provided data on adverse effects to provide high-certainty evidence. More, rigorously designed, large-scale studies are needed to definitively conclude if lithium is superior to other interventions in treating acute mania.


Assuntos
Antipsicóticos , Transtorno Bipolar , Compostos de Lítio , Doença Aguda , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Humanos , Compostos de Lítio/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Valproico/uso terapêutico
13.
J Trauma Acute Care Surg ; 87(2): 393-401, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31206419

RESUMO

BACKGROUND: Although damage control resuscitation (DCR) is routinely performed for short durations, prolonged DCR may be required in military conflicts as a component of prolonged field care. Valproic acid (VPA) has been shown to have beneficial properties in lethal hemorrhage/trauma models. We sought to investigate whether the addition of a single dose of VPA to a 72-hour prolonged DCR protocol would improve clinical outcomes. METHODS: Fifteen Yorkshire swine (40-45 kg) were subjected to lethal (50% estimated total blood volume) hemorrhagic shock (HS) and randomized to three groups: (1) HS, (2) HS-DCR, (3) HS-DCR-VPA (150 mg/kg over 3 hours) (n = 5/cohort). In groups assigned to receive DCR, Tactical Combat Casualty Care guidelines were applied (1 hour into the shock period), targeting a systolic blood pressure of 80 mm Hg. At 72 hours, surviving animals were given transfusion of packed red blood cells, simulating evacuation to higher echelons of care. Survival rates, physiologic parameters, resuscitative fluid requirements, and laboratory profiles were used to compare the clinical outcomes. RESULTS: This model was 100% lethal in the untreated animals. DCR improved survival to 20%, although this was not statistically significant. The addition of VPA to DCR significantly improved survival to 80% (p < 0.01). The VPA-treated animals also had significantly (p < 0.05) higher systolic blood pressures, lower fluid resuscitation requirements, higher hemoglobin levels, and lower creatinine and potassium levels. CONCLUSION: VPA administration improves survival, decreases resuscitation requirements, and improves hemodynamic and laboratory parameters when added to prolonged DCR in a lethal hemorrhage model.


Assuntos
Ressuscitação/métodos , Choque Hemorrágico/terapia , Ácido Valproico/uso terapêutico , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/mortalidade , Suínos , Ferimentos e Lesões/complicações , Ferimentos e Lesões/tratamento farmacológico , Ferimentos e Lesões/terapia
14.
Seizure ; 70: 43-48, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31252363

RESUMO

PURPOSE: There are conflicting data regarding the drug dose that is sufficient to achieve seizure control as well as the parameters of seizure remission in juvenile myoclonic epilepsy (JME). The present study aimed to identify factors that contribute to seizure control in JME and to evaluate factors associated with JME remission and the efficacy of low-dose valproic acid (VPA) therapy. METHODS: This retrospective, cross-sectional study included a total of 215 patients (121 female and 94 male; mean age: 28.03 ±â€¯8.43 [14-59] years) diagnosed with JME. The patients were divided into remission and refractory groups. Remission was defined as a seizure-free (myoclonic, absence, and/or generalized tonic-clonic) period of at least 2 years. Patients in whom remission was achieved with VPA monotherapy were further divided into two groups according to the use of low-dose VPA therapy (VPA ≤ 750 mg/day and >750 mg/day). Potential contributing factors were evaluated in terms of the relationship between the dose and the remission parameters. RESULTS: Remission was achieved with VPA monotherapy in 116 patients (87.9%) in the remission group; the VPA dose was ≤750 mg in 77.6% of the patients. The dose of VPA was higher in patients with absence seizure who achieved remission (p = 0.026). Remission was achieved with a lower dose of VPA in females than in males (p = 0.004). CONCLUSIONS: Low-dose VPA can be used to achieve remission in JME. However, identification at follow-up visits of the factors that may affect remission may change the planned effective dose of VPA.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Mioclônica Juvenil/tratamento farmacológico , Ácido Valproico/uso terapêutico , Adolescente , Adulto , Estudos Transversais , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações na Gravidez/tratamento farmacológico , Estudos Retrospectivos , Fatores Sexuais , Resultado do Tratamento , Adulto Jovem
15.
Croat Med J ; 60(2): 71-77, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31044578

RESUMO

AIM: To test the hypothesis that valproic acid treatment positively affects brain-derived neurotrophic factor (BDNF) expression and DNA methylation in the hippocampus and brain cortex of rats simultaneously treated with aldosterone. METHODS: Male Sprague-Dawley rats (N=40) were treated for two weeks with valproic acid (100 mg/1 kg body weight/d) in drinking water and aldosterone (2 µg/100 g body weight/d) or placebo via subcutaneous osmotic minipumps. RESULTS: Treatment with valproic acid did not modify BDNF gene expression in the hippocampus but reduced BDNF mRNA levels in the brain cortex. Valproic acid treatment marginally enhanced global DNA methylation in the frontal cortex. BDNF expression negatively correlated with DNA methylation in the hippocampus of valproic acid-treated rats. An unexpected finding was that aldosterone treatment significantly decreased global DNA methylation in the hippocampus. CONCLUSION: The effect of valproic acid on BDNF expression in the brain may depend on the extent of pathological changes present at the time of treatment onset. The observed negative correlation between BDNF expression and DNA methylation in the hippocampus of valproic acid-treated rats encourages further studies.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Metilação de DNA/efeitos dos fármacos , Depressão/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Ácido Valproico/farmacologia , Aldosterona , Animais , Encéfalo/metabolismo , Córtex Cerebral/metabolismo , Depressão/induzido quimicamente , Modelos Animais de Doenças , Hipocampo/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Ácido Valproico/uso terapêutico
17.
Neurology ; 92(20): e2339-e2348, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31068480

RESUMO

OBJECTIVE: Compare the cost and effectiveness of nonbenzodiazepine antiepileptic drugs (non-BZD AEDs) for treatment of BZD-resistant convulsive status epilepticus (SE). METHODS: Decision analysis model populated with effectiveness data from a systematic review and meta-analysis of the literature, and cost data from publicly available prices. The primary outcome was cost per seizure stopped ($/SS). Sensitivity analyses evaluated the robustness of the results across a wide variation of the input parameters. RESULTS: We included 24 studies with 1,185 SE episodes. The most effective non-BZD AED was phenobarbital (PB) with a probability of SS of 0.8 (95% confidence interval [CI]: 0.69-0.88), followed by valproate (VPA) (0.71 [95% CI: 0.61-0.79]), lacosamide (0.66 [95% CI: 0.51-0.79]), levetiracetam (LEV) (0.62 [95% CI: 0.5-0.73]), and phenytoin/fosphenytoin (PHT) (0.53 [95% CI: 0.39-0.67]). In pairwise comparisons, PB was more effective than PHT (p = 0.002), VPA was more effective than PHT (p = 0.043), and PB was more effective than LEV (p = 0.018). The most cost-effective non-BZD AED was LEV (incremental cost-effectiveness ratio [ICER]: $18.55/SS), followed by VPA (ICER: $94.44/SS), and lastly PB (ICER: $847.22/SS). PHT and lacosamide were not cost-effective compared to the other options. Sensitivity analyses showed marked overlap in cost-effectiveness, but PHT was consistently less cost-effective than LEV, VPA, and PB. CONCLUSION: VPA and PB were more effective than PHT for SE. There is substantial overlap in the cost-effectiveness of non-BZD AEDs for SE, but available evidence does not support the preeminence of PHT, neither in terms of effectiveness nor in terms of cost-effectiveness.


Assuntos
Anticonvulsivantes/uso terapêutico , Estado Epiléptico/tratamento farmacológico , Anticonvulsivantes/economia , Benzodiazepinas/uso terapêutico , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Humanos , Lacosamida/economia , Lacosamida/uso terapêutico , Levetiracetam/economia , Levetiracetam/uso terapêutico , Fenobarbital/economia , Fenobarbital/uso terapêutico , Fenitoína/análogos & derivados , Fenitoína/economia , Fenitoína/uso terapêutico , Falha de Tratamento , Ácido Valproico/economia , Ácido Valproico/uso terapêutico
19.
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
20.
Neurología (Barc., Ed. impr.) ; 34(4): 224-228, mayo 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-180811

RESUMO

Introducción: La epilepsia ausencia infantil (EAI) se considera una forma de epilepsia de fácil control farmacológico solo si se emplean criterios estrictos para la clasificación de los pacientes. Supone el 10% de las epilepsias infantiles de inicio antes de los 15 años y es más frecuente en niñas escolares. El objetivo es conocer la evolución a largo plazo de los pacientes atendidos en la etapa infantil con EAI empleando los criterios de Loiseau y Panayiotopoulos Métodos: Estudio retrospectivo de 69 pacientes con EAI con edad actual mayor de 11 años, realizado mediante revisión de historias clínicas, EEG y cuestionario telefónico. Resultados: Cumplieron los criterios de Loiseau y Panayiotopoulos 52 pacientes, edad actual media 17,61 años. Relación mujeres/hombres: 1,65/1; edad de inicio media: 6 años y 2 meses; duración total de tratamiento media: 3 años y 9 meses; antecedentes familiares de epilepsia: 30,8%; antecedentes personales de crisis febriles: 7,7%; tipo de ausencias: simples 73,5·%, complejas: 26,5%; respuesta al primer tratamiento: ácido valproico 46,3% o ácido valproico con etosuximida simultáneos 90,9%; respuesta al segundo tratamiento (etosuximida o lamotrigina) 84,2%; crisis tras supresión de tratamiento: 4%; pacientes en remisión terminal: 78,8%; necesidad de apoyo psicopedagógico: 25%. Conclusiones: Nuestros datos muestran la utilidad de clasificar a los pacientes utilizando criterios estrictos ya que el pronóstico de las crisis del síndrome de EAI puro es excelente. Encontramos que la tasa de recaídas ha sido muy baja. A pesar del favorable pronóstico en cuanto al control de crisis necesitan apoyos psicopedagógicos en un alto porcentaje


Introduction: Childhood absence epilepsy (CAE) is considered easily manageable with medication provided that a strict patient classification system is employed. It accounts for 10% of all childhood epilepsy cases starting before the age of 15 and it is most frequent in school-aged girls. The aim of this study is to analyse long-term outcomes of patients diagnosed with CAE according to the Loiseau and Panayiotopoulos criteria and treated during childhood. Methods: We conducted a retrospective study including 69 patients with CAE who are currently older than 11; data were gathered from medical histories, EEG records, and telephone questionnaires. Results: 52 patients met the Loiseau and Panayiotopoulos criteria. Mean age is now 17.16 years. Female-to-male ratio was 1.65:1; mean age at onset was 6 years and 2 months; mean duration of treatment was 3 years and 9 months. A family history of epilepsy was present in 30.8% of the patients and 7.7% had a personal history of febrile convulsions. Absence seizures were simple in 73.5% of the patients and complex in 26.5%. Response rates to first-line treatment were as follows: valproic acid, 46.3%; and valproic acid plus ethosuximide, 90.9%. The rate of response to second-line therapy (ethosuximide or lamotrigine) was 84.2%; 4% of the patients experienced further seizures after treatment discontinuation, 78.8% achieved seizure remission, and 25% needed psychological and academic support. Conclusions: Our data show that epileptic patients should be classified according to strict diagnostic criteria since patients with true CAE have an excellent prognosis. The relapse rate was very low in our sample. Despite the favourable prognosis, psychological and academic support is usually necessary


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Epilepsia Tipo Ausência/epidemiologia , Ácido Valproico/uso terapêutico , Anticonvulsivantes/uso terapêutico , Etossuximida/uso terapêutico , Epilepsia Tipo Ausência/tratamento farmacológico , Estudos Retrospectivos , Assistência de Longa Duração/estatística & dados numéricos , Epilepsia Generalizada/epidemiologia
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