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1.
Rev Fac Cien Med Univ Nac Cordoba ; 76(4): 261-263, 2019 12 04.
Artigo em Espanhol | MEDLINE | ID: mdl-31833750

RESUMO

Introduction: The typical aura without headache is a type of migraine with aura regularly assessed by ophthalmology. It is defined as at least two recurrent attacks, lasting from 5 to 60 minutes, of reversible, visual, sensorial and / or language unilateral neurological symptoms.Methods: We present a case report of a male with typical aura without headache. Results: Male with a history of migraine without aura in adolescence and without vascular risk factors. Referred from ophthalmology by biweekly episodes characterized by central teicopsia that progressively covers the entire visual field in 20 minutes, without being influenced by opening or closing eyes, which disappears after 40 minutes from the beginning. The episodes are not stereotyped, they are not followed by headache, nor do they associate other neurological symptoms. Neurological examination and complementary tests were normal. It is concluded in favor of typical aura without headache and after six months of starting treatment with Lamotrigine there were no recurrences. Final conclusion: The diagnosis of typical aura without headache begins with an adequate anamnesis. Due to the nature of its manifestations it is necessary to differentiate it from other etiologies such as transient ischemic attacks and focal seizures due to the diagnostic, therapeutic and prognostic implications. It may appear, as in this case, in patients with migraine without aura. Lamotrigine is an excellent therapeutic option in the typical aura without headache.


Assuntos
Enxaqueca com Aura/diagnóstico , Idoso , Humanos , Lamotrigina/uso terapêutico , Masculino , Enxaqueca com Aura/tratamento farmacológico
2.
Clin Biochem ; 74: 24-30, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31672648

RESUMO

BACKGROUND: In some clinical situations (pregnancy, aging, drug resistance, toxicity), measurements of lamotrigine plasma levels may be reliable. Limited studies indicate that saliva and hair could be alternative sources for monitoring lamotrigine therapy. The drug content in hair can also be used to assess the history of drug therapy and to ascertain long-term patient compliance. The aims of this study were to 1) determine the correlations among plasma, saliva, and hair lamotrigine concentrations, 2) evaluate saliva as an alternative matrix for monitoring drug levels and 3) evaluate hair as a source of information on adherence to antiepileptic treatment and on the correlation of hair concentrations with clinical outcomes in patients with epilepsy. METHODS: Plasma, saliva, and hair lamotrigine concentrations were measured by liquid chromatography-tandem mass spectrometry in positive ionization mode. The study group (n = 85) was recruited among the epileptic patients at the Institute of Psychiatry and Neurology, Warsaw, Poland. RESULTS: Plasma concentrations were not influenced by sex, age, or the concomitant use of other antiepileptic drugs. Lamotrigine saliva and plasma concentrations were strongly correlated (r = 0.82, p < 0.001). Lamotrigine hair concentrations were correlated with the plasma concentrations (r = 0.53, p < 0.001) and daily dose in mg/kg (r = 0.23, p = 0.024). The analysis revealed no significant correlation between lamotrigine hair levels and the number of seizures in the previous 3 months (r = -0.1, p > 0.05). CONCLUSIONS: The lamotrigine saliva concentration is strongly correlated with its plasma level, and saliva can be used as an alternative matrix to plasma for monitoring. Lamotrigine can also be successfully measured in hair, and the drug levels in hair tend to be correlated with the levels in plasma. However, lamotrigine levels in hair may not correspond to clinical outcomes (i.e., seizure episodes).


Assuntos
Anticonvulsivantes/análise , Monitoramento de Medicamentos/métodos , Cabelo/química , Lamotrigina/análise , Saliva/química , Adolescente , Adulto , Idoso , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/sangue , Anticonvulsivantes/uso terapêutico , Cromatografia Líquida , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Feminino , Humanos , Lamotrigina/administração & dosagem , Lamotrigina/sangue , Lamotrigina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polônia , Convulsões/sangue , Convulsões/tratamento farmacológico , Espectrometria de Massas em Tandem , 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.
Tohoku J Exp Med ; 248(4): 273-284, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31447473

RESUMO

Lamotrigine, a frequently used antiepileptic drug, inhibits voltage-gated sodium-channels. By suppressing the release of glutamate and aspartate, lamotrigine acts as a membrane stabilizer, and it is also effective in bipolar disorder and migraine. However, lamotrigine is known to induce tremor among 4-10% of patients. We examined the lamotrigine-induced tremor in 28 epilepsy patients (age: 38.06 ± 13.56 years; 24 females and 4 males) receiving lamotrigine monotherapy and compared the data to 30 age- and sex-matched controls (age: 33.06 ± 10.71 years; 25 females and 5 males). Tremor was visually assessed by clinical tremor rating scales. Quantitative characteristics (intensity, center frequency and frequency dispersion) which are regularly used to differentiate various tremor syndromes were measured by validated, sensitive biaxial accelerometry in resting, postural and intentional positions. Regularity of repetitive finger and hand movements and reaction time were also determined. Data were statistically analyzed. Clinical tremor rating scales detected pathological tremor in three patients (10%), while accelerometry revealed tremor in seven patients (25%). Center frequency of patients with pathological tremor was similar to controls, but the frequency dispersion was significantly lower and tremor intensity was significantly higher in both postural and intentional positions. Rhythmic movements and reaction time were normal. Our results show that objective measurements detect pathological intention tremor in 25% of epilepsy patients receiving lamotrigine monotherapy. Quantitative characteristics suggest the involvement of the cerebellum in the pathomechanism of lamotrigine-induced tremor. Determining the parameters of drug-induced tremor syndromes might help to understand the complex action of tremor generator networks.


Assuntos
Cerebelo/patologia , Epilepsia/tratamento farmacológico , Lamotrigina/efeitos adversos , Lamotrigina/uso terapêutico , Tremor/induzido quimicamente , Adulto , Estudos de Casos e Controles , Cerebelo/efeitos dos fármacos , Epilepsia/sangue , Feminino , Humanos , Lamotrigina/sangue , Modelos Logísticos , Masculino , Tremor/sangue
6.
World Neurosurg ; 132: 314-320, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31449994

RESUMO

BACKGROUND: Whereas transient, self-limiting seizures are an infrequent but known complication of deep brain stimulation (DBS) implantation surgery, stimulation itself has occasionally been reported to result in seizure activity at delayed time points. The neural circuitry implicated in stimulation-induced seizures is unknown. CASE DESCRIPTION: A 47-year-old woman underwent chronic subcallosal cingulate DBS for treatment of refractory anorexia nervosa and experienced seizure with stimulation onset. Supratherapeutic voltage caused a generalized seizure. The patient subsequently experienced a full recovery. We reviewed the literature for other cases of delayed postoperative DBS seizures associated with stimulation. We also investigated whether the higher voltage may have recruited networks implicated in epilepsy. The supratherapeutic voltage stimulated a larger area and engaged vulnerable networks, including bilateral hippocampi, cingulate gyrus, and temporal lobes. Literature review identified 20 studies reporting delayed seizure after DBS surgery, 13 of which demonstrated a robust association with mostly nonmotor DBS stimulation. CONCLUSIONS: Nonmotor DBS targets, particularly in patients with epilepsy, may be more vulnerable to stimulation-induced seizures; as such, extra caution should be used when programming stimulation parameters at these DBS targets.


Assuntos
Anorexia Nervosa/terapia , Encéfalo/fisiopatologia , Estimulação Encefálica Profunda/efeitos adversos , Convulsões/etiologia , Anticonvulsivantes/uso terapêutico , Encéfalo/diagnóstico por imagem , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Humanos , Lamotrigina/uso terapêutico , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Convulsões/diagnóstico por imagem , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologia
7.
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
8.
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
10.
Bipolar Disord ; 21(7): 595-610, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31077521

RESUMO

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


Assuntos
Anticonvulsivantes/uso terapêutico , Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/psicologia , Comorbidade , Humanos , Lamotrigina/uso terapêutico , Compostos de Lítio/uso terapêutico , Fumarato de Quetiapina/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias/psicologia , Topiramato/uso terapêutico , Ácido Valproico/uso terapêutico
11.
Psiquiatr. biol. (Internet) ; 26(1): 38-40, ene.-abr. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-185026

RESUMO

Clásicamente la epilepsia y la depresión se han visto estudiadas y relacionadas. Esta correlación se traduce en la práctica clínica con una elevada incidencia de comorbilidades psiquiátricas en los pacientes diagnosticados de epilepsia, en especial con los trastornos afectivos unipolares. A su vez, ambas entidades se han observado como secuela medio-tardía tras encefalitis por virus herpes simple (VHS). Se presenta el caso clínico de un varón de 30 años diagnosticado de depresión mayor recurrente de aparición tras un episodio de encefalitis vírica por VHS-1 a los 16 años de edad. Tras varios cambios y combinaciones de fármacos antidepresivos se objetiva una respuesta satisfactoria al tratamiento con ISRS y lamotrigina


The link between epilepsy and depression has been studied and confirmed by many papers. This correlation has its clinical importance given the high incidence of psychiatric comorbidities commonly found in patients diagnosticated of epilepsy, particularly unipolar affective disorder. Both pathologies are also described as a medium-long term sequelae of HSV encephalitis. In this case report, the diagnosis of major depression in a 30-year old man who undergoes HSV-1 encephalitis is analyzed. After many switches of antidepressant treatment, the combination of Lamotrigine and SNRIs turned out to be the most successful


Assuntos
Humanos , Masculino , Adulto , Encefalite/complicações , Epilepsia/complicações , Transtorno Depressivo Maior/psicologia , Viroses do Sistema Nervoso Central/complicações , Antidepressivos/uso terapêutico , Lamotrigina/uso terapêutico , Simplexvirus/patogenicidade , Transtornos do Humor/psicologia
12.
J Pak Med Assoc ; 69(3): 442-444, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30890845

RESUMO

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


Assuntos
Anticonvulsivantes/uso terapêutico , Neoplasias Encefálicas/terapia , Epilepsia/tratamento farmacológico , Glioma/terapia , Neoplasias Encefálicas/complicações , Quimioterapia Combinada , Epilepsia/etiologia , Gabapentina/uso terapêutico , Glioma/complicações , Humanos , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Gradação de Tumores , Fenitoína/uso terapêutico , Taxa de Sobrevida , Topiramato/uso terapêutico , Ácido Valproico/uso terapêutico , Zonisamida/uso terapêutico
13.
World Neurosurg ; 126: 601-604, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30880214

RESUMO

BACKGROUND: Childhood absence epilepsy is a common generalized epilepsy syndrome characterized by childhood onset of frequent sporadic absence seizures. During onset, the electroencephalogram exhibits bilateral, symmetric, and synchronous discharges of approximately 3 Hz of generalized spike-and-wave complexes. Focal spikes are often found in children with focal epilepsy but are not common in absence epilepsy. CASE DESCRIPTION: In the case patient, focal spikes were observed during active onset of absence epilepsy and at 5 years after the first hospital visit, at which time absence epilepsy was controlled and medication was withdrawn without focal seizure attack in the interim. CONCLUSIONS: This case demonstrates that focal spikes associated with childhood absence epilepsy do not require specific treatment in the absence of focal seizures.


Assuntos
Epilepsia Tipo Ausência/fisiopatologia , Potenciais de Ação , Anticonvulsivantes/uso terapêutico , Criança , Substituição de Medicamentos , Eletroencefalografia , Epilepsia Tipo Ausência/diagnóstico por imagem , Epilepsia Tipo Ausência/tratamento farmacológico , Seguimentos , Humanos , Lamotrigina/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Transtornos Intrínsecos do Sono/fisiopatologia , Ácido Valproico/uso terapêutico , Gravação em Vídeo
14.
Paediatr Drugs ; 21(1): 15-24, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30734897

RESUMO

Childhood absence epilepsy (CAE) is a common pediatric epilepsy syndrome with distinct seizure semiology, electroencephalography (EEG) features, and treatment. A diagnosis of CAE can be obtained during an office visit with a careful history, physical exam including prolonged hyperventilation, and a routine EEG. The treatment of choice for CAE with absence seizures only is ethosuximide. Valproic acid and lamotrigine are also effective treatments for many patients, but when compared to ethosuximide, valproic acid has more adverse effects and lamotrigine is less effective. Attention to predictors of response to treatment, including clinical, electrographic, and genetic factors, is increasing. Refractory CAE occurs in fewer than half of patients, and treatment strategies are available, though efficacy data are lacking. Careful assessment and treatment of psychosocial comorbidities is essential in caring for patients with CAE.


Assuntos
Epilepsia Tipo Ausência/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Eletroencefalografia , Epilepsia Tipo Ausência/diagnóstico , Etossuximida/uso terapêutico , Feminino , Humanos , Lamotrigina/uso terapêutico , Masculino , Guias de Prática Clínica como Assunto , Convulsões/tratamento farmacológico , Resultado do Tratamento , Ácido Valproico/uso terapêutico
15.
Cochrane Database Syst Rev ; 2: CD003032, 2019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30734919

RESUMO

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


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Tipo Ausência/tratamento farmacológico , Etossuximida/uso terapêutico , Lamotrigina/uso terapêutico , Ácido Valproico/uso terapêutico , Adolescente , Anticonvulsivantes/efeitos adversos , Criança , Etossuximida/efeitos adversos , Humanos , Lamotrigina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Valproico/efeitos adversos
16.
Ther Drug Monit ; 41(3): 401-404, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30688868

RESUMO

BACKGROUND: Lamotrigine has become the most frequently prescribed drug in the treatment of pregnant women with epilepsy. Although some relevant studies have found a wide milk/maternal serum as well as infant/maternal serum concentration ratio, different infant ages at the time of sampling and small number of patients preclude comparison. The aim of this study was to provide a consistent evaluation. METHODS: Data of 43 nursing women treated by lamotrigine were evaluated retrospectively. The authors followed the transport of lamotrigine during the first postnatal month from mothers to breastfed infants through maternal milk between the years 2002 and 2017. RESULTS: Lamotrigine concentrations varied from 1.1 to 14.9 mg/L in the maternal serum, from <0.66 to 9.1 mg/L in the milk and between <0.66 and 6.9 mg/L in the infant serum. The milk/maternal serum concentration ratio ranged from <0.18 to 0.74 and the infant/maternal serum concentration ratio measured between <0.15 and 0.74. Highly significant correlations were found between milk and maternal serum levels and between infant serum levels and milk, maternal serum levels, lamotrigine daily dose, and also maternal dose related to the body weight. CONCLUSIONS: The authors confirmed the wide range of the milk/maternal serum concentration ratio and the infant/maternal serum concentration ratio. Although the degree of lamotrigine exposure to the breastfed infants was smaller than during gestation, 16% of the infant serum levels measured were within the therapeutic range used for the general epileptic population. Lamotrigine concentration monitoring in breastfed infant, in our opinion, is the most relevant aspect for the analysis of actual lamotrigine exposure in infants, especially in those with clinical symptoms.


Assuntos
Anticonvulsivantes/sangue , Anticonvulsivantes/metabolismo , Lamotrigina/sangue , Lamotrigina/metabolismo , Leite Humano/metabolismo , Anticonvulsivantes/uso terapêutico , Aleitamento Materno/métodos , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Feminino , Humanos , Recém-Nascido , Lamotrigina/uso terapêutico , Mães , Gravidez , Estudos Retrospectivos , Soro/química
17.
Chin Med J (Engl) ; 132(3): 269-274, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30681492

RESUMO

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


Assuntos
Acidose Láctica/tratamento farmacológico , Acidose Láctica/mortalidade , Anticonvulsivantes/uso terapêutico , Levetiracetam/uso terapêutico , Encefalomiopatias Mitocondriais/tratamento farmacológico , Encefalomiopatias Mitocondriais/mortalidade , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Adolescente , Carbamazepina/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lamotrigina/uso terapêutico , Levetiracetam/administração & dosagem , Masculino , Oxcarbazepina/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Topiramato/uso terapêutico , Ácido Valproico/uso terapêutico
18.
J Affect Disord ; 246: 418-421, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30599363

RESUMO

BACKGROUND: Lamotrigine is a useful treatment in bipolar depression but requires several weeks of dose titration before its clinical effects can be assessed. Animal experimental studies suggest that lamotrigine lowers glutamate release. The aim of the current study was to assess the effect of lamotrigine on brain glutamate in depressed bipolar patients and to determine whether baseline glutamate could be used to predict clinical response. METHODS: We studied 21 bipolar patients who received lamotrigine treatment for a current episode of depression. Before starting lamotrigine and after 10-12 weeks treatment, patients underwent proton magnetic resonance spectroscopy (MRS) scanning at 3 Tesla where levels of glutamate (measured as Glx) were determined in anterior cingulate cortex (ACC). RESULTS: Overall, lamotrigine treatment had no significant effect on Glx levels in ACC. However, in patients who responded clinically to lamotrigine treatment Glx concentrations were significantly increased. Baseline levels of Glx did not predict response to lamotrigine. LIMITATIONS: The main limitation of the study was the modest sample size. Most patients were medicated which may have modified the effect of lamotrigine on glutamate activity. MRS at 3T cannot give a reliable estimate of glutamate separate from its main metabolite, glutamine, and thus changes in Glx may not give a precise estimate of effects of lamotrigine on glutamate itself. CONCLUSION: Lamotrigine does not appear to have a direct effect on glutamate levels in ACC in bipolar patients. However, therapeutic improvement during lamotrigine was associated with increased Glx, suggesting that alterations in glutamatergic activity might be related to recovery from bipolar depression.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Encéfalo/metabolismo , Ácido Glutâmico/metabolismo , Lamotrigina/uso terapêutico , Espectroscopia de Prótons por Ressonância Magnética , Adulto , Transtorno Bipolar/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
19.
Am J Ther ; 26(1): e96-e102, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30601211

RESUMO

BACKGROUND: Lamotrigine (LAM), an antiepileptic, with panoply of indications and uses in neurology, is FDA approved, in psychiatry, for bipolar prophylaxis. Apart from this indication, trend of its use in psychiatry is on the rise addressing a multitude of disorders. STUDY QUESTION: LAM remains one of only few psychotropic drugs with antiglutamate activity. This might render LAM a potential therapeutic option in treatment-resistant major psychiatric disorders. We reviewed LAM pharmacology and its diverse indications while examining the extant evidence. METHODS: EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systemic Reviews were searched for all relevant studies up to date of June 2016. RESULTS: Sound evidence supports use of LAM for acute bipolar depression and prophylaxis, treatment-resistant schizophrenia, treatment-resistant obsessive-compulsive disorder, posttraumatic stress disorder, depersonalization disorder, and affective dysregulation and behavioral dyscontrol domains of borderline personality disorder. Less compelling evidence is present for use in behavioral and psychological symptoms of dementia and neuropsychiatric sequelae of traumatic brain injury. No evidence supports use in autism spectrum disorder or acute unipolar depression. CONCLUSIONS: LAM is an important addition to the psychopharmacological armamentarium. Level of evidence supporting the use of LAM in off-label indications is highly variable, and hence, sound clinical judgment is necessary for its proper use and placement in real-life psychiatric practice and psychopharmacotherapy algorithms.


Assuntos
Anticonvulsivantes/uso terapêutico , Uso de Medicamentos , Lamotrigina/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Uso Off-Label , Humanos
20.
PLoS One ; 14(1): e0210600, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30645607

RESUMO

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


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Lamotrigina/uso terapêutico , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Carbamazepina/uso terapêutico , Criança , Pré-Escolar , China , Quimioterapia Combinada , Epilepsia/etnologia , Feminino , Humanos , Lamotrigina/sangue , Lamotrigina/farmacocinética , Masculino , Pessoa de Meia-Idade , Oxcarbazepina/uso terapêutico , Estudos Retrospectivos , Topiramato/uso terapêutico , Triazinas/uso terapêutico , Ácido Valproico/uso terapêutico , Adulto Jovem
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