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Data on single-substance exposures to lamotrigine reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System in 2000 and 2001 were retrospectively analyzed.
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This study presents an analysis of all cases of refractory epilepsy evaluated at the epilepsy unit of San Juan de Dios Hospital from August, 2012 to October, 2014.
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We review recent studies and new concepts on the electroclinical features and pathophysiological findings of childhood absence epilepsy in order to highlight areas of consensus as well as areas of uncertainty that indicate directions for future research.
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Valproate is an anticonvulsive drug whose mechanism of action is based on GABAergic systems. One of the infrequent adverse effects of valproate is choreiform movements. In our study, we report a patient having head trauma history with partial and secondary generalized seizures taking 1500 mg/day valproate. During the second month of the therapy, generalized chorea was observed. Since other aetiologic causes of chorea were excluded, acutely occurring chorea in the patient was thought to be related with valproate usage because of persistence of choreiform movements for days without any fluctuation. Valproate was stopped slowly and lamotrigine was added at a dose of 400 mg/day. Within a two-month period after cessation of the valproate, choreiform movements had disappeared. We thought that the history of head trauma and another antiepileptic drug usage were the risk factors for the occurrence of valproate-induced choreiform movements.
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For some drugs, this approach offers a low-cost method of therapeutic index estimation. Our results can serve as preliminary data for future trials and as guidance for US Food and Drug Administration decision making regarding narrow therapeutic index classification.
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The SUNCT syndrome refers to Short-lasting Unilateral Neuralgiform headache with Conjunctival injection and Tearing. It is characterized by brief attacks of severe unilateral pain in the orbitotemporal region, associated with ipsilateral cranial autonomic disturbances. All SUNCT patients experience ipsilateral conjunctival injection and lacrimation. Mean age of onset is 50 years with a male predominance. The syndrome is often misdiagnosed as trigeminal neuralgia or cluster headache. Primary and secondary forms exist, the secondary form is most commonly associated with lesions of the posterior fossa or pituitary adenoma. The SUNCT syndrome is refractory to most commonly employed therapies. Lamotrigine has recently been reported as an effective first line therapy.
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To evaluate the efficacy and safety of aripiprazole (ARI) plus lamotrigine (LTG) compared with placebo (PBO) plus LTG, for long-term treatment in bipolar I disorder patients with a recent manic/mixed episode.
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Our objective was to identify clinical, medication, and demographic factors associated with seizure recurrence in medically treated patients with epilepsy receiving one of four antiepileptic monotherapy regimens: lamotrigine, levetiracetam, oxcarbazepine, or topiramate.
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Healthy subjects (n = 16) completed 4 test days involving the administration of lamotrigine, 300 mg by mouth, or placebo 2 hours prior to administration of ketamine (0.26 mg/kg by intravenous bolus and 0.65 mg/kg per hour by intravenous infusion) or placebo in a randomized order under double-blind conditions. Behavioral and cognitive assessments were performed at baseline and after administration of the medications.
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Incubation of patient lymphocytes, with or without murine hepatic microsomes with anticonvulsants or SMX. The viability of lymphocytes was based on SDH activity that can be measured spectrophotometrically. The percentage of cells displaying cytotoxicity compared to controls (cells treated only with drug) was calculated. Seventy-two immunocompetent and 16 immunocompromised (HIV) patients with DHS to SMX were sampled. The results were validated vs. 26 controls that had not experienced DHS to SMX. Sixty-two patients who had DHS to anticonvulsants were compared with 24 controls that did not have any DHS to the same anticonvulsants.
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The authors believe this to be the first double-blind placebo-controlled randomization study to test the efficacy of lamotrigine in the management of outpatients with DPDs. These need to be replicated in a larger study group.
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Lamotrigine is an anticonvulsant drug used to treat partial and generalized seizure disorders. Hypersensitivity to lamotrigine usually causes mild symptoms such as fever, rash, and slight invasion of internal organs. However, a 33-year-old male patient who was admitted with Stevens-Johnson syndrome after taking lamotrigine for 15 days experienced hepatic failure and died 5 days after admission. This case demonstrates the importance of realizing that lamotrigine can lead to fatal hepatic failure, and that tests for the normal liver function should be performed when administering lamotrigine.
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A total of 129 papers were eligible for analyses. Our findings indicate that the majority of the CNS-acting drugs, if taken by nursing women, result in average exposure levels to their breast-fed infants of less than 10% of the therapeutic doses per kg body weight. Exceptions are lithium, ethosuximide, phenobarbital, primidone, lamotrigine and topiramate. Adverse effect profiles do not always correlate with a higher exposure level. Overall, most reported adverse effect profiles appear benign. Where adverse effects were reported, they were often confounded by intrauterine exposure.
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According to paired t-test analyses, the mean CGI-CB score significantly decreased from 7.2 ± 2.7 at baseline to 3.8 ± 2.5 at Week 12. Likewise, the mean score for Clinical Global Impression of Bipolar Disorder-Severity scale significantly decreased from 4.7 ± 0.9 at baseline to 3.1 ± 1.2 at Week 12. Analysis of covariance showed that the extent to which CGI-CB scores changed from baseline to Week 12 did not significantly differ between patients with bipolar I and II disorder. However, the change in CGI-CB scores between Weeks 4 and 12 was significantly smaller in bipolar II patients than bipolar I patients. A total of 21 (21.4%) patients dropped out during the course of the study, and 30 patients (30.6%) reported 82 adverse events.
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Fifty-four patients were identified with a male:female ratio of 2.4:1 with age range of 10 months to 14 years. A history of febrile convulsion was found in 11 (20%) patients, history of infantile spasm was found in 14 patients (26%), mental retardation in 52 patients (96%), and hypotonia in 13 patients (24%). All patients had abnormal EEG that meets the diagnostic criteria. Brain CT scan was abnormal in 32 (65%) patients. Brain MRI was abnormal in 17 (23%) patients. Neuroradiological abnormalities varied from non-specific atrophy to hippocampal sclerosis and calcification. Metabolic screening carried out for 11 patients (20%) was normal. All patients were on a 3-drug combination at some stage of their disease. The most frequent combination was sodium valproate and lamotrigine. Intravenous immunoglobulin was used in 2 patients with temporary improvement; ketogenic diet was tried in one patient, which did not add much to fit control.
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The present study describes the effect of nebivolol (NBV) either alone or in combination with lamotrigine (LTG) using increasing current electroshock seizures (ICES) model in mice.
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We report our experience with lamotrigine add-on therapy in the treatment of 11 patients with Lennox-Gastaut syndrome. Lamotrigine is a novel antiepileptic drug, chemically unrelated to the major anticonvulsants in current use. Ten patients experienced a > 50% reduction in seizure frequency, 1 patient experienced no change in seizure frequency. All patients tolerated lamotrigine satisfactorily and no side-effects were reported.
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本文对meta 分析（meta-analysis, MA）作了简要概述，并着重于经典的固定效应和随机效应MA模型。文章以综合分析5项使用拉莫三嗪治疗双相障碍抑郁发作的研究的公开数据为范例，介绍了MA模型的应用及免费软件R在meta分析中的使用方法，该meta分析证实拉莫三嗪的效果优于安慰剂，且有统计学显著性，而在单个的研究中此优势并不明显。.
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Although much progress has been made in successfully treating bipolar disorder, there is increasing awareness of the limitations of traditional treatment regimes, such as lithium or antipsychotics and the possible beneficial use of antiepileptic drugs. After the first generation of antiepileptic drugs such as phenytoin and clonazepam, the second generation is comprised of the frequently-used substances carbamazepine/oxcarbazepine and valproate. Lamotrigine, gabapentin, tiagabine, levetiracetam, zonisamide and topiramate will represent the third generation 5 years from now. Drugs such as retigabine might represent the next generation. However, the efficacy of antiepileptic drugs investigated in the treatment of bipolar disorder differs and most promising effects are seen in combination therapy with mood stabilizers. The authors review the main mechanisms of action of these drugs which may, in turn, improve our understanding of the pathophysiology of bipolar disorder.
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22.7% of epileptic outpatients in Spain are diagnosed with DRE in clinics of neurology. These will require certain social interventions and greater use of health resources, including treatment with more appropriate AEDs. Pregabaline, oxcarbazepine, levetiracetam and topiramate are among the most effective AEDs in this type of patients.
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This article is a bibliographic review of the part currently played by antiepileptic drugs in the treatment of neuropathic pain, and knowledge of their specific actions according to the different physiopathogenic mechanisms suspected of being involved in this type of pain.
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Approximately half of all patients with diagnosed bipolar disorder are prescribed 2 or more psychotropic medications. Lamotrigine was approved in 2003 for the maintenance treatment of bipolar I disorder. This study examined comparative effects of lamotrigine with and without concomitant medications.
To describe and assess the evidence from controlled trials on the efficacy and tolerability of anticonvulsants for preventing migraine attacks in adult patients with migraine.
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The aim of this observational study was to obtain information regarding efficacy and safety of add-on levetiracetam (LEV; n=32) in Japanese patients with refractory partial seizures in an everyday clinical setting, relative to control AEDs (n=30). This is the first study of LEV add-on therapy conducted in Japan since approval was made. The medical charts of patients were retrospectively reviewed. The efficacy variables were seizure freedom and ≥50% reduction in seizure frequency. A significantly higher response to LEV was demonstrated in patients with all seizure types at baseline, relative to control AEDs. In patients with a duration of epilepsy of at least 10 years, significant effects in response to LEV were demonstrated with regards to efficacy variables, relative to control AEDs, thus providing meaningful results. Only two patients (6.2%) discontinued LEV treatment due to worsening of seizures, but no discontinuation was reported due to adverse events. LEV as add-on therapy to other AEDs is a promising useful treatment option for patients with refractory partial seizures without notable effects on safety, indicating that this treatment regimen might be recommended for such patients.
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Twenty-four patients with hypersensitivity reactions, e.g. drug-induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms (DIHS/DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), following the administration of anticonvulsant drugs, and 24 patients who had used anticonvulsant drugs but did not have hypersensitivity reactions (the control group) were included in this study. Peripheral blood mononuclear cells were isolated. The cells were stimulated with the drugs, phytohemagglutinin as a mitogen and Candida as an antigen (positive controls). Lymphocyte proliferation was measured using the BrdU proliferation assay kit (Roche, Germany). The stimulation index was calculated as the mean ratio of the OD of stimulated cells divided by the OD of unstimulated cells. The results in the case and control groups were compared.
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There are some indications that seizure activity promotes the development of stroke-like episodes, or vice versa, in patients with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome or other syndromic mitochondrial disorders. A 41-year-old Caucasian female with MELAS syndrome, presenting with short stature, microcytic anaemia, increased blood-sedimentation rate, myopathy, hyper-gammaglobulinaemia, an iron-metabolism defect, migraine-like headaches, and stroke-like episodes, developed complex partial and generalised seizures at age 32 years. Valproic acid was ineffective but after switching to lamotrigine and lorazepam, she became seizure-free for five years and stroke-like episodes did not recur. Cerebral MRI initially showed enhanced gyral thickening and a non-enhanced T2-hyperintensity over the left parieto-temporo-occipital white matter and cortex and enhanced caudate heads. After two years without seizures, the non-enhanced hyperintense parieto-temporo-occipital lesion had disappeared, being attributed to consequent seizure control. The caudate heads, however, remained hyperintense throughout the observational period. This case indicates that adequate seizure control in a patient with MELAS syndrome may prevent the recurrence of stroke-like episodes and may result in the disappearance of stroke-like lesions on MRI.
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2,2,3,3-Tetramethylcyclopropanecarbonylurea (TMCU) is an amide derivative of a tetramethylcyclopropyl analogue of valproic acid (VPA), one of the leading antiepileptic drugs. Structural considerations used in the design of TMCU aimed to enhance the anticonvulsant potency of VPA and to prevent its two life-threatening side effects; i.e., teratogenicity and hepatotoxicity. The anticonvulsant activity of TMCU was evaluated in the MES, scMet, 6-Hz, scBic and scPic tests, and also in the hippocampal kindling model of partial seizures and lamotrigine-resistant amygdala kindling model of therapy-resistant seizures. Minimal motor impairment was determined using the rotorod test in mice and the positional sense test, muscle tone test, and gait and stance test in rats. The antinociceptive effect of TMCU was evaluated in the mouse formalin model of acute-tonic pain. The molecular mechanisms of action of TMCU were investigated in electrophysiological studies using the whole-cell patch-clamp technique. Teratogenicity studies were performed in a SWV/Fnn-mouse model of VPA-induced teratogenicity. TMCU hepatotoxicity was evaluated following 1-week intraperitoneal and oral administration of 50, 250 and 500 mg/kg doses to rats. In the hepatotoxicity study the blood levels of TMCU were evaluated at day 1 and day 7 of the treatment. TMCU mutagenicity was evaluated in the Ames test.
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In an open, observational, add-on study design, 125 resident patients with severe therapy-resistant epilepsy and multiple additional handicaps were treated with lamotrigine in titrated doses. Seizure types, monthly seizure frequency, seizure severity, and psychological status were recorded during a 3-month baseline and a 3-month lamotrigine treatment period prior to the key date of this analysis (31 March 1996).
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Approximately 40%-70% of neuroleptic-resistant schizophrenic patients are nonresponders even to clozapine. Several clozapine augmentation strategies have come into clinical practice, although often without evidence-based support. This study aims to critically review all the reported case studies regarding the efficacy and safety of adjunctive agents in clozapine-resistant schizophrenic or schizoaffective patients. All published case studies examining the efficacy and safety of adjunctive agents in clozapine-resistant schizophrenic patients were searched for in the MEDLINE database from January 1980 to February 2004. Case studies regarding ECT as a clozapine augmentation strategy were not included in our study. All the included papers were critically reviewed and examined against a set of clinical and pharmacological parameters, outcome measures, and reported side effects. Fifteen case studies regarding the efficacy and safety of sulpiride, risperidone, olanzapine, lithium, lamotrigine, fluvoxamine, and bromocriptine as clozapine adjuncts were found. A total of 33 schizophrenic or schizoaffective patients were included. Of the 15 studies, 8 were associated with risperidone. The duration and dosage of previous clozapine monotherapy was adequate for 16 patients. Plasma clozapine level was assessed for only 7 patients. Outcome measures were used for only 11 patients. The outcome was positive in 13 studies. Combined treatments were generally well tolerated, and side effects never resulted in discontinuation of treatment. Most case studies favor the use of risperidone as an adjunctive agent in clozapine-resistant schizophrenic or schizoaffective patients. However, small numbers of patients and other methodological shortcomings limit the impact of evidence provided.
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This study evaluated the efficacy and safety of lamotrigine in binge-eating disorder (BED) associated with obesity. Fifty-one outpatients with BED by Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria, and obesity were randomized to receive either lamotrigine (N=26) or placebo (N=25) in a 16-week, double-blind, flexible-dose study. Lamotrigine (236+/-150 mg/day) and placebo had similar rates of reduction of weekly frequency of binge-eating episodes and binge days, weight and BMI, measures of eating pathology, obsessive-compulsive symptoms, impulsivity, and global severity of illness. However, lamotrigine was associated with a numerically greater amount of weight loss (1.17 vs. 0.15 kg) and significant reductions in fasting levels of glucose, insulin, and triglycerides. It was also well tolerated and associated with no serious adverse events. As a result of an exceptionally high placebo response, it is likely that for efficacy measures except for body weight and metabolic indices, the study was incapable of detecting potentially clinically important drug-placebo difference.