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1.
Yonsei Med J ; 61(10): 875-879, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32975062

RESUMO

PURPOSE: To describe adverse drug reactions (ADRs) to carbamazepine (CBZ) and oxcarbazepine (OXC), including severe cutaneous ADRs, at a tertiary care hospital over a 10-year period. MATERIALS AND METHODS: The frequency and clinical features of ADRs caused by CBZ and OXC were analyzed using the pharmacovigilance database and spontaneous ADR reporting data of Yonsei University Severance Hospital & Dental Hospital (Seoul, Korea) from January 1, 2010 to January 31, 2020. RESULTS: Among 10419 cases prescribed CBZ and OXC, 204 ADR cases were reported. The incidences of ADRs were 1.8% and 2.2% for CBZ and OXC respectively, with no significant difference (p=0.169). The most common clinical presentations were skin disorders. Female patients had relatively more frequent ADRs than male patients. Although mild skin ADRs were more frequent with OXC, nervous system disorders, general disorders, and hepatobiliary disorders occurred more often with CBZ. There were six reports of severe cutaneous adverse reactions to CBZ, while OXC had none. Both CBZ and OXC caused ADRs at daily doses lower than the recommended initial dose. CONCLUSION: Due to lower incidence of severe ADRs with OXC than CBZ, we suggest OXC as a first-line prescription.


Assuntos
Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Oxcarbazepina/efeitos adversos , Adolescente , Adulto , Idoso , Anticonvulsivantes/uso terapêutico , Transtorno Bipolar , Carbamazepina/uso terapêutico , Epilepsia/tratamento farmacológico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neuralgia , Oxcarbazepina/uso terapêutico , Farmacovigilância , República da Coreia/epidemiologia , Centros de Atenção Terciária , Adulto Jovem
2.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(7): 782-789, 2020 Jul 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879081

RESUMO

OBJECTIVES: Due to the narrow therapeutic window of valproic acid (VPA), grievous adverse reactions such as hepatotoxicity, nephrotoxicity may occur in patients with epilepsy for a long time. This study aimed to explore the effect of VPA concentration on biochemical and routine blood test related to liver, renal, and hematology in epileptic outpatients treated with VPA alone or combined with other antiepileptic drugs. METHODS: A total of 3 194 Chinese epileptic outpatients from Xiangya Hospital, were analyzed in a crude analysis after stratifying through dosage regimens. The plasma VPA concentration was detected by gas chromatography method and then standardized through dosage and body weight. Ten biochemical indexes related to liver, renal, and hematology were evaluated. RESULTS: Of all patients, blood urea nitrogen (BUN), serum creatinine (SCr) level, and erythrocyte count (RBC) showed positive correlations with standardized VPA concentration (r=0.494, r=0.157, r=0.596, respectively), while platelet specific volume (PCT) and blood platelet (PLT) showed negative correlations with standardized VPA concentration (r=-5.500, r=-0.086, respectively). After stratifying through dosage regimens, significantly positive associations between SCr and standardized VPA concentration were found in the juvenile patients from the monotherapy group and combination therapy group (r=1.800, r=0.352, respectively). In addition, PLT and leukocyte count (WBC) in the juvenile patients from the combination therapy group were negatively correlated with standardized VPA concentration (r=-1.463, r=-0.079, respectively), while RBC showed a positive association with standardized VPA concentration in the juvenile patients from the monotherapy group (r=0.068). CONCLUSIONS: SCr level is significantly associated with plasma VPA concentration. Drug combination and age are important factors leading to hematological disorders. The finding provides potential theoretical guidance for the rational and safe clinical use of VPA.


Assuntos
Epilepsia/tratamento farmacológico , Ácido Valproico/uso terapêutico , Adolescente , Anticonvulsivantes/uso terapêutico , Terapia Combinada , Quimioterapia Combinada , Humanos , Pacientes Ambulatoriais
4.
Lancet Neurol ; 19(9): 784-796, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32822636

RESUMO

Trigeminal neuralgia is a very painful neurological condition with severe, stimulus-evoked, short-lasting stabbing pain attacks in the face. The past decade has offered new insights into trigeminal neuralgia symptomatology, pathophysiology, and treatment, leading to a change in the classification of the condition. An accurate diagnosis is crucial because neuroimaging interpretation and clinical management differ among the various forms of facial pain. MRI using specific sequences should be a part of the diagnostic workup to detect a possible neurovascular contact and exclude secondary causes. Demonstration of a neurovascular contact should not be used to confirm a diagnosis but rather to facilitate surgical decision making. Carbamazepine and oxcarbazepine are drugs of first choice for long-term treatment, whereas microvascular decompression is the first-line surgery in medically refractory patients. Advances in neuroimaging techniques and animal models will provide further insight into the causes of trigeminal neuralgia and its pathophysiology. Development of more efficacious treatment options is highly warranted.


Assuntos
Gerenciamento Clínico , Neuralgia do Trigêmeo/diagnóstico por imagem , Neuralgia do Trigêmeo/fisiopatologia , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Carbamazepina/farmacologia , Carbamazepina/uso terapêutico , Descompressão Cirúrgica/métodos , Humanos , Neuroimagem/métodos , Oxcarbazepina/farmacologia , Oxcarbazepina/uso terapêutico , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Neuralgia do Trigêmeo/classificação , Neuralgia do Trigêmeo/terapia
6.
Artigo em Russo | MEDLINE | ID: mdl-32790974

RESUMO

OBJECTIVE: To evaluate the changes of epileptiform activity index (EAI) as a measure of the efficacy and tolerability of treatment with valproic acid (VA) in patients with newly-diagnosed generalized and focal epilepsy. MATERIAL AND METHODS: The study included 93 patients (55 men and 38 women): 27 with focal epilepsy (FE) and 66 with idiopathic generalized epilepsy (IGE). Patients with idiopathic and age-dependent FE were not included in the study. At each visit, video-EEG monitoring with the analysis of focal, diffuse and generalized epileptiform activity during wakefulness before sleep, during sleep, after sleep and during partial awakenings with quantitative EAI assessment at baseline, after 1, 3, 6 and 12 months of therapy was performed. Therapeutic drug monitoring was performed during dose titration 1 month after the start of treatment or in case of treatment change. Treatment efficacy was assessed based on the absence of seizures, decrease of seizure episodes by more than 50% (responders) and <50% (insufficient efficacy). Adverse effects (AE) were assessed using the Assessing SIDe effects in AED treatment scale (SIDAED). RESULTS: Maximal EAI was observed at baseline both in FE and IGE groups. In patients with IGE, the total EAI (52.8±7.8) was significantly higher compared to FE group (27.1±5.5 (p=0,027)). During wakefulness before sleep and during sleep EAI was significantly lower in the IGE group compared to FE patients (3.4±0. vs. 10.5±5.5 (p=0.003) and 4.3±0.8 vs. 8.9±3.7 (p=0.046), respectively). VA demonstrated the high efficacy and good tolerability in IGE and FE patients: after 12 months of treatment remission was achieved in 69 (74.2%) patients, the decrease of seizure frequency by more than 50% was observed in 22 (23,7%) patients, insufficient efficacy only in 2 (2.1%). AEs were registered only sporadically. CONCLUSIONS: VA remains one of the drugs of choice in IGE and FE. EAI may become an additional objective test in cases of difficult differential diagnosis in IGE and FE, using total EAI, EAI before sleep, during sleep, during partial awakenings in the first months of treatment (1-3 months). EAI objectively reflects the dynamics of VA treatment efficacy.


Assuntos
Epilepsias Parciais/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Epilepsia/tratamento farmacológico , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Eletroencefalografia , Feminino , Humanos , Masculino , Ácido Valproico/uso terapêutico
7.
Ann Afr Med ; 19(3): 164-169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32820727

RESUMO

Background: Quality of life (QOL) is a vital outcome measure in people living with epilepsy. The aim of this study is to determine the sociodemographic and clinical factors that predict poor QOL in patients with epilepsy. Materials and Methods: This is a descriptive cross-sectional study that was carried out at the outpatient psychiatric clinic of Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, Nigeria, for 6 months. Seventy-four patients with epilepsy who met the inclusion criteria were recruited to participate in the study. The mental health of these patients and their QOL were assessed using the Mini-International Neuropsychiatric Interview and the short form of the World Health Organization QOL instrument, respectively. Data were analyzed using epi-info version 6.04d, and logistic regression analysis was performed to determine factors that predict poor QOL. Results: Psychiatric disorder was found in 33 (44.6%) of the respondents. The presence of these psychiatric disorders was predictive of poor score on the overall QOL (odds ratio [OR] = 0.382; 95% confidence interval [CI] = 0.145-0.983; P = 0.0046), physical (OR = 0.269; 95% CI = 0.100-1.722; P = 0.009), and psychological health domain (OR = 0.269; 95% CI = 0.102-0.709; P = 0.008). Longer duration of epilepsy was predictive of a poor score on the health satisfaction item (OR = 0.202; 95% CI = 0.06-0.679; P = 0.010) while being single was predictive of poor score on the social relationship domain (OR = 0.177; 95% CI = 0.065-0.482; P = 0.001). Conclusion: The presence of psychiatric disorder, long duration of epilepsy, and being single were predictive of poor QOL. The importance of social relation, prompt seizure control, and efficient collaboration between psychiatrist and other medical professionals in the care of patients with epilepsy cannot be overemphasized.


Assuntos
Ansiedade/etiologia , Depressão/etiologia , Epilepsia/complicações , Epilepsia/psicologia , Qualidade de Vida/psicologia , Adulto , Anticonvulsivantes/uso terapêutico , Ansiedade/psicologia , Estudos Transversais , Depressão/psicologia , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Escalas de Graduação Psiquiátrica , Convulsões/epidemiologia , Convulsões/psicologia , Inquéritos e Questionários , Organização Mundial da Saúde
8.
Rinsho Shinkeigaku ; 60(9): 627-630, 2020 Sep 29.
Artigo em Japonês | MEDLINE | ID: mdl-32779601

RESUMO

A 17-year-old woman presented with transient consciousness impairment attack and convulsion after bathing and prolonged standing since age 12. EEG showed WHAM ( wake, high amplitude, anterior, male) type of phantom spikes that usually carry the high risk of epilepsy at age 13. At age 17, EEG wise generalized spike and wave complex was recorded once, and head-up tilt test was positive. She was carefully observed without antiepileptic drugs since convulsive syncope due to neurally mediated syncope was most likely. During the follow-up period, she had eventually unprovoked generalized tonic-clonic seizures (convulsive seizure) twice and thus she was started with antiepileptic drug with success. Although both convulsive syncope and convulsive seizure differ in nature and effects on quality of life, in this patient, the latter occurred later and both occurs together. It is important to distinguish them by means of the degree of convulsion and EEG finding.


Assuntos
Convulsões/complicações , Convulsões/diagnóstico , Síncope/complicações , Síncope/diagnóstico , Anticonvulsivantes/uso terapêutico , Criança , Diagnóstico Diferencial , Eletroencefalografia , Feminino , Humanos , Qualidade de Vida , Recidiva , Convulsões/tratamento farmacológico , Síncope/tratamento farmacológico , Teste da Mesa Inclinada , Resultado do Tratamento
9.
Lancet Neurol ; 19(9): 748-757, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32822635

RESUMO

BACKGROUND: Surgery is a widely accepted treatment option for drug-resistant focal epilepsy. A detailed analysis of longitudinal postoperative seizure outcomes and use of antiepileptic drugs for different brain lesions causing epilepsy is not available. We aimed to analyse the association between histopathology and seizure outcome and drug freedom up to 5 years after epilepsy surgery, to improve presurgical decision making and counselling. METHODS: In this retrospective, multicentre, longitudinal, cohort study, patients who had epilepsy surgery between Jan 1, 2000, and Dec 31, 2012, at 37 collaborating tertiary referral centres across 18 European countries of the European Epilepsy Brain Bank consortium were assessed. We included patients of all ages with histopathology available after epilepsy surgery. Histopathological diagnoses and a minimal dataset of clinical variables were collected from existing local databases and patient records. The primary outcomes were freedom from disabling seizures (Engel class 1) and drug freedom at 1, 2, and 5 years after surgery. Proportions of individuals who were Engel class 1 and drug-free were reported for the 11 main categories of histopathological diagnosis. We analysed the association between histopathology, duration of epilepsy, and age at surgery, and the primary outcomes using random effects multivariable logistic regression to control for confounding. FINDINGS: 9147 patients were included, of whom seizure outcomes were available for 8191 (89·5%) participants at 2 years, and for 5577 (61·0%) at 5 years. The diagnoses of low-grade epilepsy associated neuroepithelial tumour (LEAT), vascular malformation, and hippocampal sclerosis had the best seizure outcome at 2 years after surgery, with 77·5% (1027 of 1325) of patients free from disabling seizures for LEAT, 74·0% (328 of 443) for vascular malformation, and 71·5% (2108 of 2948) for hippocampal sclerosis. The worst seizure outcomes at 2 years were seen for patients with focal cortical dysplasia type I or mild malformation of cortical development (50·0%, 213 of 426 free from disabling seizures), those with malformation of cortical development-other (52·3%, 212 of 405 free from disabling seizures), and for those with no histopathological lesion (53·5%, 396 of 740 free from disabling seizures). The proportion of patients being both Engel class 1 and drug-free was 0-14% at 1 year and increased to 14-51% at 5 years. Children were more often drug-free; temporal lobe surgeries had the best seizure outcomes; and a longer duration of epilepsy was associated with reduced chance of favourable seizure outcomes and drug freedom. This effect of duration was evident for all lesions, except for hippocampal sclerosis. INTERPRETATION: Histopathological diagnosis, age at surgery, and duration of epilepsy are important prognostic factors for outcomes of epilepsy surgery. In every patient with refractory focal epilepsy presumed to be lesional, evaluation for surgery should be considered. FUNDING: None.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/cirurgia , Convulsões/tratamento farmacológico , Convulsões/prevenção & controle , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Epilepsia Resistente a Medicamentos/patologia , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/patologia , Resultado do Tratamento , Adulto Jovem
10.
Medicine (Baltimore) ; 99(29): e19800, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702807

RESUMO

RATIONALE: Cerebral cavernous malformation (CCM) of the familial type is caused by abnormalities in the CCM1, CCM2, and CCM3 genes. These 3 proteins forming a complex associate with the maintenance of vascular endothelial cell-cell junctions. Dysfunction of these proteins results in the development of hemangiomas and abnormal intercellular junctions. PATIENT CONCERNS: We report a 68-year-old man with familial cerebral cavernous malformation with initial presentation as convulsions at an advanced age. Brain magnetic resonance imaging revealed multiple cavernous hemangiomas in the right occipital lobe. The convulsions were considered to be induced by hemorrhage from cavernous hemangioma in the right occipital lobe. DIAGNOSES: Genetic screening of the CCM1, CCM2, and CCM3 genes revealed a novel mutation in the CCM2 gene (exon4 c: 359 T>A, p: V120D). No abnormalities were found in CCM1 or CCM3. Therefore, we diagnosed the patient with familial CCM caused by a CCM2 mutation. INTERVENTIONS: This patient was treated with the administration of levetiracetam at a dosage of 1000 mg/day. OUTCOMES: No seizures have been observed since the antiepileptic drug was administered. We performed brain magnetic resonance imaging (MRI) regularly to follow-up on appearance of new cerebral hemorrhages and cavernous hemangiomas. LESSONS: This report reviews cases of familial cerebral cavernous malformations caused by abnormalities in the CCM2 gene. This mutation site mediates interactions with CCM1 and CCM3. The mutation occurs in the phosphotyrosine binding (PTB) site, which is considered functionally important to CCM2.


Assuntos
Proteínas de Transporte/genética , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemorragia/diagnóstico por imagem , Idoso , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Testes Genéticos , Hemangioma Cavernoso/complicações , Hemangioma Cavernoso/genética , Hemangioma Cavernoso/patologia , Hemangioma Cavernoso do Sistema Nervoso Central/tratamento farmacológico , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Hemorragia/etiologia , Humanos , Levetiracetam/administração & dosagem , Levetiracetam/uso terapêutico , Imagem por Ressonância Magnética/métodos , Masculino , Mutação , Convulsões/diagnóstico , Convulsões/etiologia , Resultado do Tratamento
11.
PLoS One ; 15(7): e0235674, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649723

RESUMO

BACKGROUND: Non-adherence to anti-seizure medication (ASM) therapy is an important contributing factor to the higher mortality rate and treatment failure of epilepsy. This study aimed to determine the rate and factors associated with non-adherence to ASM therapy through the WHO five dimensions of medication adherence framework. METHODS: We conducted a cross-sectional study at an outpatient Neurology Clinic of a tertiary government hospital in Malaysia. Between March and July 2019, we identified 217 patients with a confirmed diagnosis of epilepsy, receiving oral ASM therapy and able to administer their medications. We performed a semi-structured interview to gather information on sociodemographic background, clinical and medication history, and perceptions on healthcare services. Adherence to ASM therapy was evaluated using the Medication Compliance Questionnaire (MCQ). Patient's illness perception was assessed by the Brief Illness Perception Questionnaire (B-IPQ). RESULTS: 208 patients participated in this study. The median age of the study participants was 35 years (IQR 26-44). 58.2% were females and majority, 55.8%, were from the Malay ethnic group. Based on the MCQ scoring, 89 patients (42.8%) were non-adherent. Multiple logistic regression demonstrated that being employed or students (adjusted odds ratio [aOR] 2.26, 95%CI: 1.19-4.29 p = 0.012) and having an average or below average perceived access to pharmacy services (aOR 2.94, 95%CI: 1.38-6.24, p = 0.005) were significant contributors to non-adherence. CONCLUSION: Being employed or students and having an average or below average perceived access to pharmacy services were associated with ASM non-adherence Efforts to improve ASM adherence should adopt a comprehensive approach considering the success of adherence is contingent on the interrelationship of multiple dimensions.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adulto , Área Sob a Curva , Estudos Transversais , Epilepsia/diagnóstico , Epilepsia/psicologia , Feminino , Humanos , Modelos Logísticos , Malásia , Masculino , Curva ROC , Inquéritos e Questionários , Centros de Atenção Terciária
13.
J Stroke Cerebrovasc Dis ; 29(8): 104989, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689590

RESUMO

OBJECTIVE: Identify clinical and radiographic features of venous infarct as a presenting feature of COVID-19 in the young. BACKGROUND: SARS-CoV-2 infection causes hypercoagulability and inflammation leading to venous thrombotic events (VTE). Although elderly patients with comorbidities are at higher risk, COVID-19 may also cause VTE in a broader patient population without these risks. Neurologic complications and manifestations of COVID-19, including neuropathies, seizures, strokes and encephalopathy usually occur in severe established cases of COVID-19 infection who primarily present with respiratory distress. CASE DESCRIPTION: Case report of a 29-year-old woman, with no significant past medical history or comorbidities, presenting with new onset seizures. Further questioning revealed a one-week history of headaches, low-grade fever, mild cough and shortness of breath, diagnosed as COVID-19. Imaging revealed a left temporoparietal hemorrhagic venous infarction with left transverse and sigmoid sinus thrombosis treated with full dose anticoagulation and antiepileptics. CONCLUSION: Although elderly patients with comorbidities are considered highest risk for COVID-19 neurologic complications, usually when systemic symptoms are severe, this case report emphasizes that young individuals are at risk for VTE with neurologic complications even when systemic symptoms are mild, likely induced by COVID-19 associated hypercoagulable state.


Assuntos
Betacoronavirus/patogenicidade , Infarto Encefálico/virologia , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Trombose dos Seios Intracranianos/virologia , Trombose Venosa/virologia , Adulto , Fatores Etários , Anticoagulantes/uso terapêutico , Anticonvulsivantes/uso terapêutico , Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/tratamento farmacológico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Feminino , Interações entre Hospedeiro e Microrganismos , Humanos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Fatores de Risco , Trombose dos Seios Intracranianos/diagnóstico por imagem , Trombose dos Seios Intracranianos/tratamento farmacológico , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológico
14.
Cochrane Database Syst Rev ; 7: CD007783, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32609387

RESUMO

BACKGROUND: This is an update of the Cochrane Review first published in 2010; it includes one additional study. Primary generalised tonic-clonic seizures are a type of generalised seizure. Other types of seizures include: absence, myoclonic, and atonic seizures. Effective control of tonic-clonic seizures reduces the risk of injury and death, and improves quality of life. While most people achieve seizure control with one antiepileptic drug, around 30% do not, and require a combination of antiepileptic drugs. OBJECTIVES: To assess the effectiveness and tolerability of add-on lamotrigine for drug-resistant primary generalised tonic-clonic seizures. SEARCH METHODS: For the latest update, we searched these databases on 19 March 2019: Cochrane Register of Studies (CRS) Web, MEDLINE Ovid, and the WHO International Clinical Trials Registry Platform (ICTRP). The CRS includes records from the Cochrane Epilepsy Group Specialized Register, CENTRAL, Embase, and ClinicalTrials.gov. We imposed no language restrictions. We also contacted GlaxoSmithKline, manufacturers of lamotrigine. SELECTION CRITERIA: Randomised controlled parallel or cross-over trials of add-on lamotrigine for people of any age with drug-resistant primary generalised tonic-clonic seizures. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology; two review authors independently assessed trials for inclusion, evaluated risk of bias, extracted relevant data, and GRADE-assessed evidence. We investigated these outcomes: (1) 50% or greater reduction in primary generalised tonic-clonic seizure frequency; (2) seizure freedom; (3) treatment withdrawal; (4) adverse effects; (5) cognitive effects; and (6) quality of life. We used an intention-to-treat (ITT) population for all analyses, and presented results as risk ratios (RRs) with 95% confidence intervals (CIs); for adverse effects, we used 99% CIs to compensate for multiple hypothesis testing. MAIN RESULTS: We included three studies (total 300 participants): two parallel-group studies and one cross-over study. We assessed varied risks of bias across studies; most limitations arose from the poor reporting of methodological details. We meta-analysed data extracted from the two parallel-group studies, and conducted a narrative synthesis for data from the cross-over study. Both parallel-group studies (270 participants) reported all dichotomous outcomes. Participants taking lamotrigine were almost twice as likely to attain a 50% or greater reduction in primary generalised tonic-clonic seizure frequency than those taking a placebo (RR 1.88, 95% CI 1.43 to 2.45; low-certainty evidence). The results between groups were inconclusive for the likelihood of seizure freedom (RR 1.55, 95% CI 0.89 to 2.72; very low-certainty evidence); treatment withdrawal (RR 1.20, 95% CI 0.72 to 1.99; very low-certainty evidence); and individual adverse effects: ataxia (RR 3.05, 99% CI 0.05 to 199.36); dizziness (RR 0.91, 99% CI 0.29 to 2.86; very low-certainty evidence); fatigue (RR 1.02, 99% CI 0.13 to 8.14; very low-certainty evidence); nausea (RR 1.60, 99% CI 0.48 to 5.32; very low-certainty evidence); and somnolence (RR 3.73, 99% CI 0.36 to 38.90; low-certainty evidence). The cross-over trial (26 participants) reported that 7/14 participants with generalised tonic-clonic seizures experienced a 50% or greater reduction in seizure frequency with add-on lamotrigine compared to placebo. The authors reported four treatment withdrawals, but did not specify during which treatment allocation they occurred. Rash (seven lamotrigine participants; zero placebo participants) and fatigue (five lamotrigine participants; zero placebo participants) were the most frequently reported adverse effects. None of the included studies measured cognition. One parallel-group study (N = 153) evaluated quality of life. They reported inconclusive results for the overall quality of life score between groups (P = 0.74). AUTHORS' CONCLUSIONS: This review provides insufficient information to inform clinical practice. Low-certainty evidence suggests that lamotrigine reduces the rate of generalised tonic-clonic seizures by 50% or more. Very low-certainty evidence found inconclusive results between groups for all other outcomes. Therefore, we are uncertain to very uncertain that the results reported are accurate, and suggest that the true effect could be grossly different. More trials, recruiting larger populations, over longer periods, are necessary to determine lamotrigine's clinical use.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Tônico-Clônica/tratamento farmacológico , Lamotrigina/uso terapêutico , Anticonvulsivantes/efeitos adversos , Quimioterapia Adjuvante/métodos , Tontura/induzido quimicamente , Erupção por Droga/etiologia , Exantema/induzido quimicamente , Fadiga/induzido quimicamente , Humanos , Lamotrigina/efeitos adversos , Náusea/induzido quimicamente , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sonolência
15.
Cochrane Database Syst Rev ; 7: CD001416, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32715463

RESUMO

BACKGROUND: The majority of people with epilepsy have a good prognosis, and their seizures can be well controlled with the use of a single antiepileptic agent, but up to 30% develop dug-resistant epilepsy, especially those with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCT) of zonisamide, used as an add-on treatment for focal epilepsy uncontrolled by one or more concomitant antiepileptic drug. This is an updated version of the Cochrane review previously published in 2018. OBJECTIVES: To evaluate the efficacy and tolerability of zonisamide, when used as an add-on treatment for people with focal epilepsy uncontrolled by one or more concomitant antiepileptic drugs. SEARCH METHODS: For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (September 2019). In addition, we contacted Eisai Limited (makers and licensees of zonisamide) and experts in the field, to seek any ongoing or unpublished studies. SELECTION CRITERIA: Randomised controlled trials, in which add-on zonisamide was compared with placebo or another antiepileptic drug in people with focal epilepsy, uncontrolled by one or more concomitant antiepileptic drugs. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data, assessed for risk of bias using the Cochrane 'Risk of bias' tool, and assessed the certainty of the evidence, using the GRADE approach. The primary outcome was at least a 50% reduction in total seizure frequency; the secondary outcomes were (1) tolerability; and (2) adverse effects. We used an intention-to-treat approach for our primary analyses. We estimated summary risk ratios (RRs) for each outcome. We displayed a summary of the estimates of effects and certainty of the evidence for each outcome in a 'Summary of findings' table. MAIN RESULTS: We did not find any new studies since the last version of this review. We included eight studies (1636 participants) from previous versions of this review. The overall RR with 95% confidence interval (CI) for at least a 50% reduction in seizure frequency for 300 mg to 500 mg/day of zonisamide compared to placebo was 1.90 (95% CI 1.63 to 2.22; 7 trials, 1371 participants; moderate-certainty evidence). The RR for 50% reduction in seizure frequency compared to placebo for any dose of zonisamide (100 mg to 500 mg/day) was 1.86 (95% CI 1.60 to 2.17; 7 trials, 1429 participants; moderate-certainty evidence). The number needed to treat for an additional beneficial outcome was six (95% CI 4.1 to 6.8). Two trials provided evidence of a dose-response relationship for this outcome. The RR for treatment withdrawal for 300 mg to 500 mg/day of zonisamide compared to placebo was 1.59 (95% CI 1.18 to 2.13; 6 trials, 1099 participants; moderate-certainty evidence), and for 100 mg to 500 mg/day was 1.44 (95% CI 1.08 to 1.93; 6 trials, 1156 participants; moderate-certainty evidence). The number needed to treat for an additional harmful outcome was 15 (95% CI 9.3 to 36.7). The following adverse effects were more likely to be associated with zonisamide than with placebo: ataxia (RR 3.85, 99% CI 1.36 to 10.93; 4 trials, 734 participants; low-certainty evidence); somnolence (RR 1.52, 99% CI 1.00 to 2.31; 8 trials, 1636 participants; moderate-certainty evidence); agitation (RR 2.35, 99% CI 1.05 to 5.27; 4 trials, 598 participants; low-certainty evidence); and anorexia (RR 2.74, 99% CI 1.64 to 4.60; 6 trials, 1181 participants; low-certainty evidence). Across the eight studies, we rated risk of bias domains at low or unclear risk of bias, apart from two studies, which we rated at high risk of attrition bias. Five of the eight studies were sponsored by the drug companies that produced zonisamide. AUTHORS' CONCLUSIONS: When used as an add-on treatment in people with focal epilepsy, uncontrolled by one or more concomitant antiepileptic drugs, moderate-certainty evidence found that zonisamide was more successful than placebo at reducing the frequency of seizures by at least 50%. We were unable to identify minimum effective and maximum tolerated doses. The included trials evaluated a maximum stable-dose phase of 18 weeks, so results cannot be used to confirm longer periods of efficacy in seizure control. The results cannot be extrapolated to monotherapy, or to people with other seizure types or epilepsy syndromes.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Zonisamida/uso terapêutico , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Quimioterapia Combinada/métodos , Humanos , Análise de Intenção de Tratamento , Números Necessários para Tratar , Ensaios Clínicos Controlados Aleatórios como Assunto , Falha de Tratamento , Zonisamida/administração & dosagem , Zonisamida/efeitos adversos
16.
Cochrane Database Syst Rev ; 7: CD007302, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32730657

RESUMO

BACKGROUND: This is an updated version of the original Cochrane Review published in 2008 and updated in 2013. Epilepsy is a common neurological condition which affects up to 1% of the population. Approximately 30% of people with epilepsy do not respond to treatment with currently available drugs. The majority of these people have focal epilepsy. Vigabatrin is an antiepileptic drug licensed for use in drug-resistant epilepsy. OBJECTIVES: To assess the efficacy and tolerability of vigabatrin as an add-on therapy for people with drug-resistant focal epilepsy. SEARCH METHODS: For the latest update of this review, we searched the following databases on 1 November 2018: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid 1946 to 31 October 2018), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. The Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL) are both included in the Cochrane Register of Studies (CRS Web). We checked reference lists of retrieved studies for additional reports of relevant studies and contacted Hoechst Marion Roussel (manufacturers of vigabatrin) in 2000. SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled, fully published trials of vigabatrin in people of any age with drug-resistant focal epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors assessed trials for inclusion and extracted data using the standard methodological procedures expected by Cochrane. Primary analysis was by intention-to-treat (ITT). We evaluated: 50% or greater reduction in seizure frequency, treatment withdrawal, adverse effects, dose-response analysis, cognitive outcomes and quality of life. We presented results as risk ratios (RR) with 95% or 99% confidence intervals (CI). MAIN RESULTS: We identified 11 trials that included 756 participants (age range: 10 to 64 years). The trials tested vigabatrin doses between 1 g/day and 6 g/day. All 11 trials displayed a risk of bias across at least three risk of bias domains. Predominantly, the risk of bias was associated with: allocation concealment (selection bias), blinding of outcome assessment (detection bias) and incomplete outcome data (attrition bias). Participants treated with vigabatrin may be two to three times more likely to obtain a 50% or greater reduction in seizure frequency compared with those treated with placebo (RR 2.60, 95% CI 1.87 to 3.63; 4 studies; low-certainty evidence). Those treated with vigabatrin may also be three times more likely to have treatment withdrawn although we are uncertain (RR 2.86, 95% CI 1.25 to 6.55; 4 studies; very low-certainty evidence). Compared to placebo, participants given vigabatrin were more likely to experience adverse effects: dizziness/light-headedness (RR 1.74, 95% CI 1.05 to 2.87; 9 studies; low-certainty evidence), fatigue (RR 1.65, 95% CI 1.08 to 2.51; 9 studies; low-certainty evidence), drowsiness (RR 1.70, 95% CI 1.18 to 2.44; 8 studies) and depression (RR 3.28, 95% CI 1.30 to 8.27; 6 studies). Although the incidence rates were higher among participants receiving vigabatrin compared to those receiving placebo, the effect was not significant for the following adverse effects: ataxia (RR 2.76, 95% CI 0.96 to 7.94; 7 studies; very low-certainty evidence), nausea (RR 3.57, 95% CI 0.63 to 20.30; 4 studies), abnormal vision (RR 1.64, 95% CI 0.67 to 4.02; 5 studies; very low-certainty evidence), headache (RR 1.23, 95% CI 0.79 to 1.92; 9 studies), diplopia (RR 1.76, 99% CI 0.94 to 3.30) and nystagmus (RR 1.53, 99% CI 0.62 to 3.76; 2 studies; low-certainty evidence). Vigabatrin had little to no effect on cognitive outcomes or quality of life. AUTHORS' CONCLUSIONS: Vigabatrin may significantly reduce seizure frequency in people with drug-resistant focal epilepsy. The results largely apply to adults and should not be extrapolated to children under 10 years old. Short-term follow-up of participants showed that some adverse effects were associated with its use. Analysis of longer-term observational studies elsewhere, however, has demonstrated that vigabatrin use can lead to the development of visual field defects.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsias Parciais/tratamento farmacológico , Vigabatrina/uso terapêutico , Adolescente , Adulto , Anticonvulsivantes/efeitos adversos , Criança , Tontura/induzido quimicamente , Quimioterapia Combinada , Fadiga/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Nistagmo Patológico/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Convulsões/tratamento farmacológico , Vigabatrina/efeitos adversos , Transtornos da Visão/induzido quimicamente , Adulto Jovem
18.
Seizure ; 80: 53-55, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32540636
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