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1.
Artigo em Russo | MEDLINE | ID: mdl-33834728

RESUMO

The article is a short review of an observational study that proves the good efficacy and tolerability of perampanel suspension in the adjunctive treatment of epilepsy in children over 4 years of age. The study demonstrated a high level of 50% responders: 47% with focal seizures, 65% with transition of focal seizures to bilateral tonic-clonic seizures, 65% with primary generalized tonic-clonic seizures. Cessation of seizures was achieved in 12%, 19% and 55% of patients, respectively. The most common side-effects were fatigue (26%), nasopharyngitis (19%), lightheadedness, irritability, fever (13% each), and vomiting (11%). There were no significant clinical negative changes in cognitive functions according to the assessment on the Aldenkamp-Baker scale, both on the total score and subscales. Also, there were no significant changes in laboratory data, vital functions and ECG parameters.


Assuntos
Anticonvulsivantes , Epilepsia Tônico-Clônica , Anticonvulsivantes/efeitos adversos , Criança , Epilepsia Tônico-Clônica/tratamento farmacológico , Humanos , Piridonas/efeitos adversos , Convulsões/tratamento farmacológico , Resultado do Tratamento
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(4): 356-362, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33840407

RESUMO

OBJECTIVE: To systematically evaluate the efficacy and safety of levetiracetam (LEV) versus phenytoin (PHT) as second-line drugs for the treatment of convulsive status epilepticus (CSE) in children. METHODS: English and Chinese electronic databases were searched for the randomized controlled trials comparing the efficacy and safety of LEV and PHT as second-line drugs for the treatment of childhood CSE. RevMan 5.3 software was used for data analysis. RESULTS: Seven studies with 1 434 children were included. The Meta analysis showed that compared with the PHT group, the LEV group achieved a significantly higher control rate of CSE (RR=1.12, 95%CI:1.00-1.24, P=0.05), but there was no significant difference between the two groups in the recurrence rate of epilepsy within 24 hours (RR=0.82, 95%CI:0.22-3.11, P=0.77) and the rate of further antiepileptic drug therapy (RR=0.97, 95%CI:0.64-1.45, P=0.87). There was no significant difference in the incidence rate of adverse events between the two groups (RR=0.77, 95%CI:0.55-1.09, P=0.15). CONCLUSIONS: LEV has a better clinical effect than PHT in the treatment of children with CSE and does not increase the incidence rate of adverse events.


Assuntos
Preparações Farmacêuticas , Estado Epiléptico , Anticonvulsivantes/efeitos adversos , Criança , Humanos , Levetiracetam/uso terapêutico , Fenitoína/efeitos adversos , Estado Epiléptico/tratamento farmacológico
5.
Int J Mol Sci ; 22(4)2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671463

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to coronavirus disease 2019 (COVID-19) which, in turn, may be associated with multiple organ dysfunction. In this review, we present advantages and disadvantages of cannabidiol (CBD), a non-intoxicating phytocannabinoid from the cannabis plant, as a potential agent for the treatment of COVID-19. CBD has been shown to downregulate proteins responsible for viral entry and to inhibit SARS-CoV-2 replication. Preclinical studies have demonstrated its effectiveness against diseases of the respiratory system as well as its cardioprotective, nephroprotective, hepatoprotective, neuroprotective and anti-convulsant properties, that is, effects that may be beneficial for COVID-19. Only the latter two properties have been demonstrated in clinical studies, which also revealed anxiolytic and antinociceptive effects of CBD (given alone or together with Δ9-tetrahydrocannabinol), which may be important for an adjuvant treatment to improve the quality of life in patients with COVID-19 and to limit post-traumatic stress symptoms. However, one should be aware of side effects of CBD (which are rarely serious), drug interactions (also extending to drugs acting against COVID-19) and the proper route of its administration (vaping may be dangerous). Clearly, further clinical studies are necessary to prove the suitability of CBD for the treatment of COVID-19.


Assuntos
Analgésicos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antivirais/uso terapêutico , Canabidiol/uso terapêutico , Analgésicos/efeitos adversos , Analgésicos/farmacologia , Animais , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacologia , Antivirais/efeitos adversos , Antivirais/farmacologia , Canabidiol/efeitos adversos , Canabidiol/farmacologia , Dronabinol/efeitos adversos , Dronabinol/farmacologia , Dronabinol/uso terapêutico , Humanos , /fisiologia , Internalização do Vírus/efeitos dos fármacos
6.
Life Sci ; 275: 119342, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33713668

RESUMO

Epilepsy is one of the most common brain disorders, affecting more than 50 million people worldwide. Although its treatment is currently symptomatic, the last generation of anti-seizure drugs is characterized by better pharmacokinetic profiles, efficacy, tolerability and safety. Lacosamide is a third-generation anti-seizure drug that stands out due to its good efficacy and safety profile. It is used with effectiveness in the treatment of partial-onset seizures with or without secondary generalization, primary generalized tonic-clonic seizures and off-label in status epilepticus. Despite scarcely performed until today, therapeutic drug monitoring of lacosamide is proving to be advantageous by allowing the control of inter and intra-individual variability and promoting a successful personalized therapy, particularly in special populations. Herein, the pharmacology, pharmacokinetics, and clinical data of lacosamide were reviewed, giving special emphasis to the latest molecular investigations underlying its mechanism of action and therapeutic applications in pathologies besides epilepsy. In addition, the pharmacokinetic characteristics of lacosamide were updated, as well as current literature concerning the high pharmacokinetic variability observed in special patient populations and that must be considered during treatment individualization.


Assuntos
Anticonvulsivantes/farmacologia , Lacosamida/farmacologia , Animais , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Humanos , Lacosamida/efeitos adversos , Lacosamida/farmacocinética , Lacosamida/uso terapêutico , Neuralgia/tratamento farmacológico
7.
Epilepsy Behav ; 117: 107862, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33667843

RESUMO

OBJECTIVE: To evaluate the safety, efficacy, and tolerability of highly purified cannabidiol (CBD) for the treatment of seizures in children and adults with treatment-resistant epilepsy (TRE) in an open-label, expanded access program (EAP). METHODS: One hundred sixty-nine participants (89 children and 80 adults) with TRE received plant-derived highly purified CBD (Epidiolex® in the U.S.; 100 mg/mL oral solution) with a starting dose of 5 mg/kg/day divided twice per day and titrated to a maximum dose of 50 mg/kg/day over the study period to seizure control and tolerability and followed for up to 2 years. Seizure frequency (calendars) and severity (Chalfont Seizure Severity Score; CSSS) were collected at every study visit. Adverse Events were reported at/between study visits as required, and participants also completed Adverse Events Profile (AEP) which generates a numerical representation of AEs. Response to CBD was defined as ≥50% reduction in seizure frequency. Given non-normal distribution of seizure frequency, a log transformation was applied after which the generalized least squares regression model for longitudinal data was used. RESULTS: Evidence from the adjusted model revealed a significant mean reduction in seizure frequency compared to baseline in children and adults at all time points (1 month and 1 and 2 years). Percentage of children achieving ≥50% seizure frequency reduction was 44% at month 1, and 41% at year 1, and 61% reduction at year 2, while adult responder rates were 34% at month 1, 53% at year 1, and 71% at year 2 (all P < 0.0001). CSSS showed a sustained reduction from baseline to all 3 time points. Children displayed 52% seizure reduction at month 1, a 51% reduction at year 1, and 75% reduction at year 2. Seizure reductions in adults were 60%, 81%, and 85%, respectively (all P < 0.0001). While there were no significant differences between seizure frequency reduction between children and adults at all time points, there was a significant difference in seizure severity reduction at year 1, with adults reporting greater improvement in seizure severity (P < 0.001). The most commonly reported adverse events in the study period were diarrhea, sedation, and decreased appetite. AEP revealed significant improvement from baseline at multiple time points in adults and children, and the mean AEP scores were always lower compared to baseline over the duration of the study. SIGNIFICANCE: Our study provides further evidence of sustained seizure frequency and severity reduction over two years of treatment with highly purified CBD in TRE. In addition, CBD was generally well tolerated with minority of participants experiencing adverse events resulting in stopping CBD.


Assuntos
Canabidiol , Epilepsia Resistente a Medicamentos , Epilepsia , Adulto , Anticonvulsivantes/efeitos adversos , Canabidiol/uso terapêutico , Criança , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia/tratamento farmacológico , Humanos , Convulsões/tratamento farmacológico , Resultado do Tratamento
8.
BMJ Case Rep ; 14(3)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33692057

RESUMO

Valproic acid (VPA) is commonly used medication to treat seizure disorder and as prophylaxis for bipolar disorder. Acute VPA toxicity can cause varied symptoms ranging from mild drowsiness to severe cerebral oedema and coma. The therapeutic level of VPA is around 50-100 µg/mL and most of it is protein bound. It is mainly metabolised by liver and is eliminated via bile. The metabolites of VPA interfere with urea cycle and cause deficiency in carnitine leading to increase in ammonia levels. The use of carnitine to treat VPA toxicity is well known but it is still unclear if it lowers VPA levels. We report a case of VPA toxicity that did not respond to use of carnitine at 6000 mg orally but was successfully treated using meropenem leading to lowering of VPA levels and also clinical improvement of patient.


Assuntos
Carbapenêmicos , Epilepsia , Ácido Valproico , Adulto , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Carbapenêmicos/uso terapêutico , Carnitina/uso terapêutico , Epilepsia/tratamento farmacológico , Feminino , Humanos , Meropeném/uso terapêutico , Ácido Valproico/efeitos adversos , Ácido Valproico/uso terapêutico
10.
Mayo Clin Proc ; 96(4): 964-974, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33518408

RESUMO

OBJECTIVE: To investigate the impact of epilepsy on secondary cardiac morbidities and sudden death in patients with epilepsy. PATIENTS AND METHODS: The present cohort study evaluated data obtained from a subset of adult patients listed in the Taiwan National Health Insurance Research Database with an International Classification of Diseases, Ninth Revision, diagnosis code of epilepsy from January 1, 1997, to December 31, 2013; the date of epilepsy diagnosis or antiepilepsy drug prescription was defined as the index date. Patients with cardiac disease prior to the index date were excluded, and the remaining patients were categorized into epilepsy and nonepilepsy groups. Frequency matching was performed to balance the covariates across groups for the comparison of outcomes. The development of myocardial infarction (MI) and arrhythmia and/or the occurrence of sudden death were the outcomes for evaluation. A Cox proportional hazards regression model and competing risk analysis were used to compare the risks of cardiac morbidities and sudden death between groups. RESULTS: The final analysis included a total of 5411 patients with epilepsy and 21,644 participants without epilepsy. The epilepsy group had significantly higher risks for development of MI (hazard ratio [HR], 1.71; 95% CI, 1.62 to 1.81; P<.001) and arrhythmia (HR, 2.11; 95% CI, 1.97 to 2.25; P<.001) and the occurrence of sudden death (HR, 1.83; 95% CI, 1.53 to 2.18; P<.001) compared with the nonepilepsy group. CONCLUSION: Our results indicate that the risks for development of MI and arrhythmia and the occurrence of sudden death were higher in patients with epilepsy. These findings support the hypothesis that epilepsy may lead to secondary cardiac dysfunction and increases the risk of sudden death.


Assuntos
Anticonvulsivantes/efeitos adversos , Morte Súbita Cardíaca/epidemiologia , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Cardiopatias/induzido quimicamente , Cardiopatias/epidemiologia , Cardiopatias/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/uso terapêutico , Estudos de Coortes , Morte Súbita Cardíaca/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
11.
J Am Vet Med Assoc ; 258(5): 510-514, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33620240

RESUMO

CASE DESCRIPTION: A 2-year-old 5.1-kg (11.2-lb) sexually intact male Maltese was admitted because of vomiting and seizures after a known ingestion of up to 206 mg/kg (93.6 mg/lb) of lamotrigine (a commonly prescribed human antiepileptic medication) approximately 3 hours earlier. CLINICAL FINDINGS: On presentation, the dog was having a seizure; however, the seizure stopped before interventional treatment, and the dog was obtunded, tachycardic, and hypertensive. Fluid therapy was initiated, and a bolus of injectable lipid emulsion (ILE) was administered. The dog's cardiovascular and mentation signs improved, and the dog was hospitalized for supportive care and monitoring. Hours later, the dog developed ventricular tachycardia that progressed to ventricular fibrillation, then cardiac arrest. TREATMENT AND OUTCOME: Cardiopulmonary resuscitation, including defibrillation, was initiated. With no response after several minutes of resuscitation efforts, another bolus of ILE was administered, and the dog's heartbeat returned shortly thereafter, albeit with severe ventricular arrhythmias that were treated medically, including with sodium bicarbonate. The dog was discharged 48 hours later with no neurologic or cardiovascular abnormalities. Six months later, the owner reported that the dog was doing well and had no abnormalities. CLINICAL RELEVANCE: To our knowledge, there are no previous case reports in veterinary medicine regarding the successful use of ILE to treat cardiac arrest secondary to lipophilic drug toxicoses nor the use of and physiologic response to sodium bicarbonate during treatment of lamotrigine toxicoses in dogs; therefore, findings in the dog of the present report may help other veterinarians treating similarly affected dogs in the future.


Assuntos
Anticonvulsivantes , Doenças do Cão , Animais , Anticonvulsivantes/efeitos adversos , Doenças do Cão/induzido quimicamente , Doenças do Cão/tratamento farmacológico , Cães , Emulsões , Lamotrigina , Lipídeos , Masculino , Bicarbonato de Sódio/uso terapêutico
12.
Epilepsy Behav ; 116: 107644, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33549477

RESUMO

PURPOSE: The present study evaluated whether patients with epilepsy who received both levetiracetam (LEV) and perampanel (PER) therapy showed side effects of irritability. The study also examined the relationship between patient characteristics and irritability when it occurred as a side effect. METHODS: We retrospectively examined medical records of 98 patients with epilepsy who were treated with both LEV and PER at the Department of Psychiatry in the Epilepsy Center of Nishiniigata Chuo National Hospital in Japan. We performed multiple regression analyses with the presence/absence of irritability due to LEV or PER as the dependent variables and clinical characteristics of the patients as independent variables. RESULTS: LEV and PER caused irritability in 7 and 17 of 98 patients, respectively. LEV- and PER-related irritability did not occur in the same patients. A logistic multiple regression analysis revealed that EEG findings of temporal focal epileptic discharge were significantly associated with increased incidence of irritability due to LEV. LEV-related irritability decreased significantly with higher dosages of LEV. Another logistic multiple regression analysis revealed that a psychiatric comorbidity of irritability and EEG findings of nontemporal focal epileptic discharge were significantly associated with increased incidence of irritability due to PER. CONCLUSIONS: LEV and PER cause irritability in different patient groups. Additionally, irritability as a side effect was present only at low dosages of LEV, but PER tended to cause irritability even at high dosages.


Assuntos
Epilepsia , Piracetam , Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Humanos , Japão , Levetiracetam/uso terapêutico , Piracetam/efeitos adversos , Piridonas , Estudos Retrospectivos
13.
Epilepsy Behav ; 117: 107806, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33621813

RESUMO

This study investigated to which degree levetiracetam (LEV) and perampanel (PER), antiseizure medications (ASM) that are both known to cause aggression and irritability, share the same or different, behavioral side-effect profiles. In this self-report study, 68 participants with epilepsy treated with LEV (n = 35) or PER (n = 33) as part of their medication were asked to rate their behavioral experience with the respective drug as positive, neutral, or negative. Results of a German adaptation of the Adverse Events Profile (AEP) and of the "FPZ", a German personality questionnaire, were analyzed as a function of drug and rating. Thirty-eight percent of the LEV group and 36% of the PER group experienced negative change after the evaluated drug was introduced. By subdividing participants in the LEV sample into those who attributed the negative effects to LEV and those with neutral or positive experience with LEV, a negative evaluation of LEV was associated with significantly worse scores in cognition, mood, and physical domains (80% versus 20-40%). Subdividing participants in the PER sample into those who attributed negative the side effects to PER, and those with a neutral or positive experience with PER, significance could be shown for mood domains only (100% versus 50%), and within this domain only for increased aggression and irritability. Comparing features of the behavioral negative side effects of LEV and PER revealed that LEV appears to have a negative impact on a much broader range of behaviors than PER, which specifically seems to induce aggression and irritability and no other psychiatric side effects. Further research should aim at different expression and different mechanisms of aggression and irritability underlying the superficially similar effects of the two drugs.


Assuntos
Agressão , Piracetam , Anticonvulsivantes/efeitos adversos , Humanos , Levetiracetam/uso terapêutico , Piridonas , Autorrelato
14.
Epilepsy Behav ; 117: 107832, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33626490

RESUMO

PURPOSE: Treatment with antiseizure medications (ASMs) confers a risk of drug-induced liver injury (DILI), especially for older ASMs. We sought to quantify recent reports of DILI attributed to both older and newer generation ASMs and survey newly marketed ASMs for hepatotoxicity in a large post-marketing database. METHODS: We queried over 2.6 million adverse event reports made to the FDA Adverse Event Reporting System (FAERS) database between July 1, 2018 and March 31, 2020 for DILI due to ASMs commonly used in clinical practice. Patient characteristics and outcomes were assessed. We calculated the reporting odds ratio (ROR) of DILI for each individual ASM versus all non-ASM reports. RESULTS: A total of 2175 DILI cases were attributed to an ASM during the study period. 97.2% of these were designated as serious reactions, which include death, hospitalization, disability, and other life-threatening outcomes. A number of older and newer generation ASMs were associated with DILI, specifically: carbamazepine (ROR 2.92), phenobarbital (ROR 2.91), oxcarbazepine (ROR 2.58), phenytoin (ROR 2.40), valproate (ROR 2.22), lamotrigine (ROR 2.06), clobazam (ROR 1.67), levetiracetam (ROR 1.56), and diazepam (ROR 1.53). However, increased odds of DILI were not seen with zonisamide, perampanel, stiripentol, lacosamide, clonazepam, pregabalin, felbamate, eslicarbazepine, cannabidiol, topiramate, gabapentin, ethosuximide, brivaracetam, or primidone. Vigabatrin, tiagabine, and rufinamide all had zero reports of DILI. CONCLUSIONS: The majority of newer generation ASMs were not significantly associated with DILI. Future studies utilizing FAERS in conjunction with other data sources will be critical for the ongoing surveillance of DILI, particularly as newly marketed ASMs continue to enter into widespread clinical use.


Assuntos
Anticonvulsivantes , Doença Hepática Induzida por Substâncias e Drogas , Anticonvulsivantes/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Humanos , Lamotrigina , Levetiracetam , Fenitoína , Estados Unidos/epidemiologia
15.
Epilepsy Behav ; 117: 107846, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33626492

RESUMO

INTRODUCTION: Acute withdrawal of antiepileptic drugs (AEDs) is a safe and effective approach to provoking seizures in order to complete video-electroencephalogram (V-EEG) studies in a timely manner. Previous studies have focused only on withdrawal from conventional AEDs, and the effects of withdrawal from new-generation AEDs have not been extensively studied. MATERIALS AND METHODS: This study examined adult patients with drug-resistant epilepsy admitted to an epilepsy monitoring unit between 2015 and 2018. Patients were classified according to whether they received conventional AEDs (Con; n = 13) or new-generation AEDs (N-Gen; n = 26). We then compared the effects of withdrawing these two types of AEDs over a period of one week in terms of efficacy (time to complete V-EEG monitoring) and safety, including the incidence of cluster seizures (CS), focal to bilateral tonic-clonic seizures (FBTCS) and status epilepticus (SE). RESULTS: In both groups, approximately one week was required to complete V-EEG analysis: N-Gen group (5.6 days) and Con group (6.3 days). No differences were observed between the two groups in terms of the median number of seizures, the onset of the 1st seizure, the distribution of CS, FBTCS, or SE. Following acute withdrawal of medication, a high percentage of patients with a history of CS or FBTCS, respectively, presented CS or FBTCS. CONCLUSIONS: We did not observe significant differences between patients taking new-generation AEDs and those taking conventional AEDs following withdrawal during V-EEG recording. In the current study, we employed a standard protocol for the rapid withdrawal of AEDs (daily dose reduction of 50%), which was sufficient for 80% of patients to complete V-EEG monitoring within one week.


Assuntos
Epilepsia Resistente a Medicamentos , Estado Epiléptico , Adulto , Anticonvulsivantes/efeitos adversos , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Eletroencefalografia , Humanos , Convulsões/tratamento farmacológico , Estado Epiléptico/tratamento farmacológico
16.
Medicine (Baltimore) ; 100(7): e24343, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607769

RESUMO

BACKGROUND: Herpes zoster-associated pain [i.e., acute herpes zoster neuralgia (AHN) and postherpetic neuralgia (PHN)] has the potential to cause significant patients' burden and heath resource expenditure. PHN is refractory to the existing treatments, and the consensus is preventing the transition of AHN to PHN is better than treating PHN. Anticonvulsants (e.g., gabapentin, pregabalin) have been recommended as one of the first-line therapies for PHN. In practice, anticonvulsants have also decreased the severity and duration of AHN and reduced the incidence of PHN. Nevertheless, its clinical application to AHN is hampered by inadequate evidence for its efficacy and safety. We performed this protocol for a systematic review to explore the efficacy and safety of anticonvulsants for AHN. Besides, a benefit-risk assessment of anticonvulsants for AHN would be performed to estimate the extent to which these drugs could relieve symptoms and whether the benefits outweigh harms. METHODS: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) was used to prepare our protocol and the results will be reported according to the PRISMA. We will search the China National Knowledge Infrastructure (CNKI), Chinese VIP Information (VIP), Cochrane Library, Embase, and PubMed databases, from inception to August 2019. Furthermore, Clinicaltrials (http://www.clinicaltrials.com) and Chinese Clinical Trial Registry (http://www.chictr.org.cn/abouten.aspx) will also be searched for relevant studies. Selection of eligible articles and data extraction will be independently performed by reviewers. We will record the characteristic information, pain outcomes, incidence of PHN and adverse effects. Data synthesis and other statistical analyses will be conducted using Review Manager Software 5.3 and STATA13.0. Furthermore, risk of bias assessment, meta-regression and subgroup analyses, publication bias assessment, grading of evidence will be performed for included studies. ETHICS AND DISSEMINATION: As this systematic review will be performed based on published data, no ethical approval is needed. The findings will be submitted in peer-reviewed journals for publication. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019133449.


Assuntos
Anticonvulsivantes/administração & dosagem , Herpes Zoster/tratamento farmacológico , Neuralgia Pós-Herpética/tratamento farmacológico , Manejo da Dor/métodos , Anticonvulsivantes/efeitos adversos , Humanos , Metanálise como Assunto , Medição de Risco , Revisões Sistemáticas como Assunto
17.
Medicina (B Aires) ; 81(1): 62-68, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-33611246

RESUMO

The choice of a contraceptive method considered highly effective in epileptic women of childbearing age is important, since it requires taking into account the eligibility criteria and the possible pharmacological interactions between certain types of anti-seizure drugs (mainly enzyme inducers drugs of the hepatic system P450 such as: carbamazepine, phenytoin, phenobarbital, oxacarbamazepine, eslicarbazepine, rufinamide, lacosamide and topiramate in high doses) and certain contraceptive methods (oral contraceptives combined or only with progesterone and subdermal progesterone implants), which may accelerate the metabolism of the latter with the consequent risk of failure or vice versa, reduction of plasma concentration (such as lamotrigine) predisposing to seizures, risk of unwanted pregnancies, abortions, teratogenicity due to valproato, maternal- fetal complications and difficulty in the management of epileptic activity during pregnancy. In case of prescribing both medications, the combined use with a barrier method should be considered or the use of a depot injection of medroxyprogesterone acetate or intrauterine device as contraception should be considered. Family planning counseling at the first visit has been shown to influence the choice of the contraceptive method and the early initiation of folic acid in the search for fertility. In conclusion, the different therapeutic options should be analyzed together with the epileptic patients in order to achieve and optimize the best goal for each one.


Assuntos
Anticoncepção , Epilepsia , Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Feminino , Humanos , Gravidez , Convulsões/tratamento farmacológico
18.
Cochrane Database Syst Rev ; 1: CD003032, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33475151

RESUMO

BACKGROUND: This is an updated version of the Cochrane Review previously published in 2019. 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, 22 September 2020) and MEDLINE (Ovid, 1946 to September 21, 2020). CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. 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. individuals 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 for the outcomes 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 randomised controlled trials (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, seizure freedom was higher in patients taking ethosuximide (70/154, 45%) than in patients taking lamotrigine (31/146, 21%; P < 0.001), with no difference between valproate (64/146, 44%) and ethosuximide (70/154, 45%; P > 0.05). In this study, the frequency of treatment failures due to intolerable adverse events was significantly different among the treatment groups, with the largest proportion of adverse events in the valproic acid group (48/146, 33%) compared to the ethosuximide (38/154, 25%) and the lamotrigine (29/146, 20%) groups (P < 0.037). 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. This study provided high certainty of the evidence for outcomes for which data were available. However, the certainty of the evidence provided by the other included studies was low, primarily due to risk of bias and imprecise results because of the small sample sizes. Hence, conclusions regarding the efficacy of ethosuximide, valproic acid and lamotrigine derive mostly from this single study. 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 , Epilepsia Tipo Ausência/prevenção & controle , Etossuximida/efeitos adversos , Feminino , Humanos , Lamotrigina/efeitos adversos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Convulsões/prevenção & controle , Falha de Tratamento , Ácido Valproico/efeitos adversos
19.
Cochrane Database Syst Rev ; 1: CD001415, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33434292

RESUMO

BACKGROUND: This is an updated version of the Cochrane Review previously published in 2018. Epilepsy is a common neurological disorder characterised by recurrent seizures. Most people with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop drug-resistant epilepsy, especially people with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCTs) of gabapentin, when used as an add-on treatment for drug-resistant focal epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS: For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) on 11 August 2020. CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy. We imposed no language restrictions. SELECTION CRITERIA: Randomised, placebo-controlled, double-blind, add-on trials of gabapentin in people with drug-resistant focal epilepsy. We also included trials using an active drug control group or comparing different doses of gabapentin. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: seizure frequency, seizure freedom, treatment withdrawal (any reason) and adverse effects. Primary analyses were intention-to-treat. We also undertook sensitivity best-case and worst-case analyses. We estimated summary risk ratios (RR) for each outcome and evaluated dose-response in regression models. MAIN RESULTS: We identified no new studies for this update, therefore, the results and conclusions are unchanged. In the previous update of this review, we combined data from six trials in meta-analyses of 1206 randomised participants. The overall risk ratio (RR) for reduction in seizure frequency of 50% or more compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55; 6 studies, 1206 participants; moderate-certainty evidence). Dose regression analysis (for trials in adults) showed increasing efficacy with increasing dose, with 25.3% (95% CI 19.3 to 32.3) of people responding to gabapentin 1800 mg compared to 9.7% on placebo, a 15.5% increase in response rate (95% CI 8.5 to 22.5). The RR for treatment withdrawal compared to placebo was 1.05 (95% CI 0.74 to 1.49; 6 trials, 1206 participants; moderate-certainty evidence). Adverse effects were significantly associated with gabapentin compared to placebo. RRs were as follows: ataxia 2.01 (99% CI 0.98 to 4.11; 3 studies, 787 participants; low-certainty evidence), dizziness 2.43 (99% CI 1.44 to 4.12; 6 studies, 1206 participants; moderate-certainty evidence), fatigue 1.95 (99% CI 0.99 to 3.82; 5 studies, 1161 participants; low-certainty evidence) and somnolence 1.93 (99% CI 1.22 to 3.06; 6 studies, 1206 participants; moderate-certainty evidence). There was no evidence of a difference for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35; 6 studies, 1206 participants; moderate-certainty evidence) or nausea (RR 0.95, 99% CI 0.52 to 1.73; 4 trials, 1034 participants; moderate-certainty evidence). Overall, the studies were at low to unclear risk of bias due to information on each risk of bias domain not being available. We judged the overall certainty of the evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide CIs. AUTHORS' CONCLUSIONS: Gabapentin has efficacy as an add-on treatment in people with drug-resistant focal epilepsy, and seems to be fairly well-tolerated. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of gabapentin beyond a three-month period. The results cannot be extrapolated to monotherapy or to people with other epilepsy types. Further trials are needed to assess the long-term effects of gabapentin, and to compare gabapentin with other add-on drugs.


Assuntos
Anticonvulsivantes/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsias Parciais/tratamento farmacológico , Gabapentina/uso terapêutico , Ácido gama-Aminobutírico/uso terapêutico , Adulto , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Criança , Quimioterapia Combinada/métodos , Gabapentina/administração & dosagem , Gabapentina/efeitos adversos , Humanos , Análise de Intenção de Tratamento , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Eur J Pain ; 25(5): 1064-1071, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33428801

RESUMO

BACKGROUND: It is widely agreed that carbamazepine and oxcarbazepine are highly effective in the long-term treatment of trigeminal neuralgia. However, the tolerability of these drugs across the different aetiologies of trigeminal neuralgia is still undetermined. METHODS: In this retrospective, real-world study, we assessed the effectiveness and tolerability of carbamazepine and oxcarbazepine in a large cohort of patients with classical (254 patients), secondary (60 patients) and idiopathic (40 patients) trigeminal neuralgia. We analysed data using a propensity score analysis to account for selection bias; frequencies of side effects associated with carbamazepine and oxcarbazepine were calculated by adjusting data with the inverse probability of treatment weighting. RESULTS: The initial proportion of responders was 88.3% with carbamazepine, and 90.9% with oxcarbazepine. The number of refractory patients was significantly higher in idiopathic (15%) and secondary forms (27%) than in classical trigeminal neuralgia (6%; p < .05). In 53 patients treated with carbamazepine (29.6%) and in 22 treated with oxcarbazepine (12.6%), major side effects caused treatment interruption or dosage reduction to an unsatisfactory level. Side effects occurred more frequently in patients treated with carbamazepine (43.6%) than with oxcarbazepine (30.3%, p < .0001). The frequency of treatment discontinuation was higher in patients with secondary and idiopathic forms than in those with classical trigeminal neuralgia (p < .05). CONCLUSIONS: Our real-world study shows that carbamazepine and oxcarbazepine are effective in most patients with trigeminal neuralgia; nevertheless, side effects are still a major issue, particularly in patients with secondary and idiopathic trigeminal neuralgia. SIGNIFICANCE: Although carbamazepine and oxcarbazepine are effective in most patients with trigeminal neuralgia, their side effects are still a major issue, thus necessitating the development of better-tolerated drugs.


Assuntos
Neuralgia do Trigêmeo , Anticonvulsivantes/efeitos adversos , Benzodiazepinas/uso terapêutico , Carbamazepina/efeitos adversos , Humanos , Oxcarbazepina , Estudos Retrospectivos , Neuralgia do Trigêmeo/tratamento farmacológico
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