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Six patients (4 males and 2 females) who presented episodes of inverted metamorphopsia were studied: 4 referred right-left inversion (axial plane), 1 upwards-downwards (saggital plane) and 1 inclination of environment (clockwise movement). None had any alteration in the perception of their own bodies during the episodes which lasted from 3 minutes to 1 hour, reporting from 1 to 40 episodes. The most notable antecedents were: traumatism and forced cervical posture (2), arterial hypertension (3), migraine (2), hyperlipemia (2) and protuberantial ischemia (1).
Lamotrigine is one of the recently introduced antiepileptic drugs (AEDs) licensed in the Netherlands in 1995. The objective of this study was to examine the diffusion of lamotrigine into clinical practice. Three different aspects of this diffusion process were examined: incidence of use, patient characteristics and changes in prescription patterns in the first 5 years following its introduction.
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Nine patients were identified who had concomitant prescriptions for carbamazepine and a second-generation antipsychotic and who then discontinued carbamazepine. In only one case did the provider initially decrease the dose of the antipsychotic when carbamazepine was discontinued. Two patients experienced akathisia 3 weeks after carbamazepine was discontinued.
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Oxcarbazepine, a keto-analogue of carbamazepine, was recently approved in the United States for the treatment of seizures of partial onset. Some patients treated with oxcarbazepine showed the development of hyponatremia, which in most instances was asymptomatic. Understanding the mechanisms by which oxcarbazepine can lead to a reduction of serum sodium levels could have therapeutic implications for the few patients in whom symptomatic hyponatremia develops. In this study, we evaluated sodium and water handling in patients with epilepsy and in healthy subjects titrated over 3 weeks to a maximum daily oxcarbazepine dose of 2,400mg. All subjects were evaluated in a hospital setting after an overnight fast and after an acute water-load test performed before oxcarbazepine exposure and after maintenance on the medication for 3 weeks. Before oxcarbazepine exposure, the percentage of water load excreted was normal as both groups excreted more than 80% of the administered water load. After the intake of oxcarbazepine, the water load resulted in a reduction of the serum sodium and free water clearance without a concomitant increase in the arginine vasopressin serum levels. Most subjects in both groups failed to excrete 80% or more of the water load, suggesting that the effect of oxcarbazepine is physiological. We found that, after the water load, serum sodium and free water clearance were diminished in both groups without a concomitant increase in the arginine vasopressin serum levels. These findings indicate that oxcarbazepine-induced hyponatremia is not attributable to the syndrome of inappropriate secretion of antidiuretic hormone. Possible mechanisms include a direct effect of oxcarbazepine on the renal collecting tubules or an enhancement of their responsiveness to circulating antidiuretic hormone.
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This study shows that there are no negative interactions between the studied antiepileptic drugs and enalapril or cilazapril. Enalapril even enhanced the anticonvulsant activity of LTG in the MES test in mice that is thought to be a predictive model of human generalized tonic-clonic seizures.
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The current study was designed to investigate the effect of concomitantly administered honey on the pharmacokinetics of carbamazepine in volunteers. In a two-way cross-over design with a one-week washout period, ten healthy volunteers were randomized to receive 200 mg carbamazepine orally with 30 ml of honey or water. Blood samples were collected at 0, 0.5, 1, 2, 3, 6, 9, 12, 24, 48 and 72 h after drug administration. Carbamazepine levels were estimated by high performance liquid chromatography (HPLC). There were no statistically significant differences in the various pharmacokinetics parameters when carbamazepine was administered with honey, compared with administration with water. In conclusion, carbamazepine kinetics are not altered by honey, so epileptic patients on carbamazepine may consume honey without the risk of an interaction.
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Symptoms of alcohol withdrawal syndrome (AWS) may develop within 6-24 h after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for AWS is with benzodiazepines (BZDs). Among the BZDs, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed-dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as α2-agonists (clonidine and dexmetedomidine) and β-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptic agents can help control hallucinations. Finally, other medications for the treatment for AWS have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin and topiramate. The usefulness of these agents are discussed.
A retrospective medical record review of 60 patients with diagnostic suspicion of DRESS/DIHS admitted to our hospital between July 2008 and April 2012 was performed, including demographic data, clinical features, laboratory findings and treatment.
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Low endogenous levels of dehydroepiandrosterone (DHEA) and/or its sulfoconjugated derivative DHEA-S have been associated with diseases such as lupus, cancer, and diabetes. Circulating concentrations of DHEA and DHEA-S resulting from endogenous production or hormone supplementation may also be relevant in psychiatric illness. Drugs may significantly increase or decrease circulating concentrations of these adrenal androgens by various mechanisms. Some agents, such as dexamethasone, affect the HPA axis by inhibiting ACTH and therefore decrease DHEA and DHEA-S concentrations. Central nervous system agents, including carbamazepine and phenytoin, induce the P450 enzymes that metabolize DHEA and DHEA-S and therefore decrease circulating concentrations of these hormones. Danazol alters the ratio between DHEA and DHEA-S by inhibiting sulfatase. As research moves forward to better understand the relationships of these adrenal androgens with health and disease, it is essential that studies be designed to control for the influence of administered pharmaceuticals on DHEA and DHEA-S.
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One to seven seizures were recognized before starting CBZ or Lidocaine therapy, followed by complete cessation in 57 episodes and one or two recurrent seizures in five. Efficacy rates were 97% for CBZ-1, 100% for CBZ-3, 72.7% for LDT-1, 75% for LID-2, and 100% for Lid-iv. Efficacy was significantly higher in the CBZ groups than the Lidocaine groups (p=0.019), while the differences between treatment periods (CBZ-1 vs. CBZ-3, and Lid-1 vs. Lid-2) did not reach statistical significance (p>0.999).
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To compare vigabatrin with carbamazepine as monotherapy in newly diagnosed children with partial epilepsy in order to evaluate the efficacy and tolerability of both drugs.
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Our study demonstrates that in patients treated with VPA and CBZ, an impairment of tubular function can be present, whereas PB does not cause any significant change.
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TDM service is much less than optimal in SQUH. A lot of effort needs to be carried out to improve TDM use in the developing countries as adjusting the doses on results that are based on wrong sampling time might expose patients to toxicity or therapeutic failure.
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Therapeutic drug monitoring is an integral part of services offered by toxicology laboratories because certain drugs require routine monitoring for dosage adjustment to achieve optimal therapeutic response and avoid adverse drug reactions. Immunoassays are widely used for therapeutic drug monitoring. However, immunoassays suffer from interferences from both exogenous and endogenous compounds including metabolites of the parent drug. Digoxin immunoassays are affected more commonly than any other immunoassays used for therapeutic drug monitoring. Digoxin immunoassays are affected by endogenous digoxin-like immunoreactive substances and exogenous compounds such as various drugs, certain herbal supplements, and Digibind. Carbamazepine is metabolized to carbamazepine 10, 11-epoxide, and the crossreactivity of this metabolite with carbamazepine immunoassay may vary from 0% to 94%. Immunoassays used for measuring concentrations of tricyclic antidepressants are affected by tricyclic antidepressant metabolites and by a number of other drugs. Immunoassays for immunosuppressants are also subjected to significant interferences from metabolites, and liquid chromatography combined with mass spectrometry or tandem mass spectrometry is recommended for therapeutic drug monitoring of immunosuppressants. However, liquid chromatography combined with mass spectrometry may also suffer from interferences, for example, due to ion suppression or from isobaric ions.
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Data were extracted from the original reports individually by two reviewers. The main outcomes to be assessed were: 1. The effectiveness of valproate treatment in preventing or attenuating further episodes of bipolar disorder, including its effectiveness in rapid cycling disorder. 2. The acceptability of valproate treatment to patients. 3. The prevalence of side-effects. 4. Mortality on valproate treatment. Outcomes concerning relapse/recurrence were analysed excluding data from discontinuation studies, which were to be analysed separately. Sub-group analyses were to be performed to examine the effects of valproate treatment in rapid cycling bipolar disorder and previous mood stabiliser non-responders. Data were analysed using Review Manager version 4.1.
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A novel, sensitive and rapid CL method coupled with high-performance liquid chromatography separation for the determination of carbamazepine is described. The method was based on the fact that carbamazepine could significantly enhance the chemiluminescence of the reaction of cerium sulfate and tris(2,2-bipyridyl) ruthenium(II) in the presence of acid. The chromatographic separation was performed on a Kromasil® (Sigma-Aldrich) TM RP-C18 column (id: 150 mm × 4.6 mm, particle size: 5 µm, pore size: 100 Å) with a mobile phase consisting of methanol-water-glacial acetic acid (70:29:1, v/v/v) at a flowrate of 1.0 mL/min, the total analysis time was within 650 s. Under optimal conditions, CL intensity was linear for carbamazepine in the range 2.0 × 10(-8) ~ 4.0 × 10(-5) g/mL, with a detection limit of 6.0 × 10(-9) g/mL (S/N = 3) and the relative standard detection was 2.5% for 2.0 × 10(-6) g/mL (n = 11). This method was successfully applied to the analysis of carbamazepine in human urine and serum samples. The possible mechanism of the CL reaction is also discussed briefly.
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Unrecognized poisoning with controlled-release carbamazepine has the potential to produce significant delayed carbamazepine toxicity and delayed peak serum carbamazepine concentrations. This may occur much later than previously reported with immediate-release carbamazepine preparations.
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Of the 287 patients seen during the study period, a total of 14 (4.9%) patients were diagnosed of TN. Thirteen (4.5%) of the cases were selected based on compliance to the 8-week follow-up visits, consisting of 8 (61.5%) males and 5 (38.5%) females, giving a ratio of 1.6:1. The mean age of the patients was 50±1.5 years. The mandibular (n = 6, 46.2%) and maxillary (n = 5, 38.5%) divisions of the trigeminal nerve were mostly affected. The lesion was slightly more common on the right side of the face (n = 7, 53.8%) than the left side (n = 6, 46.2%). Talking (n=4, 30.8%) and chewing (n = 3, 23.1%) were the most frequent trigger factors. The patients mostly described the pain as severe, spontaneous, and sharp (n = 5, 38.2%). Most patients became stable on tablets carbamazepine 200 mg 12 hourly, folic acid 5 mg daily, and phenytoin 100 mg daily. Good response was observed in most patients within 2 weeks (n = 6, 46.2%) of medical treatment, especially in patients at the seventh decade of age (n = 3, 23.1%) and those with lesions involving the mandibular division of the trigeminal nerve (n = 3, 23.1%).
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LICAVAL is a single site, parallel group, randomized, outcome assessor blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic,/hypomanic or mixed episode, aged 18 to 35 years are eligible. After the diagnostic assessments, the patients are allocated for one of the groups of treatment (lithium + valproic acid or lithium + carbamazepine). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blind to the treatment. The main outcome is the evaluation of changes in mean scores on CGI-BP-M between baseline and endpoint at the end of each phase of the study.
We selected the last 100 consecutive patients with typical TN who began treatment with CBZ and the last 100 with OXC. All had MRI scans and a complete neurophysiological study of trigeminal reflexes. Among them, 22 were excluded on the basis of neuroradiological or neurophysiological investigations, to avoid the inclusion of patients with possible secondary TN. The initial number of responders was 98% with CBZ with a median dose of 600 mg (range 200-1200), and of 94% with OXC, with a median dose of 1200 mg (range 600-1800). In a mean period of 8.6 months, 27% of responders to CBZ incurred in undesired effects to a level that caused interruption of treatment or a dosage reduction to an unsatisfactory level. In a mean period of 13 months, the same occurred to 18% of responders to OXC. Among patients who had a good initial response, only 3 patients with CBZ and 2 with OXC developed late resistance. During the course of disease, paroxysms worsened in intensity in 3% of patients, and paroxysms duration increased in 2%. We did not observe the onset of a clinically manifest sensory deficit at any time in any patient.
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The case subject was 55 years old, male, mulatto, and an assistant surveyor residing in Teresina, Piauí. He presented with headache, seizures, confusion, fever and left hemiparesis upon hospitalization in 2006 at Hospital São Marcos. Five years previously, he was diagnosed with diabetes mellitus, and 17 months previously he had acne margined by hyperpigmented areas and was diagnosed with leprosy. Laboratory tests indicated leukocytosis and magnetic resonance imaging showed an infarction in the right cerebral hemisphere. Cerebrospinal fluid examination showed 120 cells/mm(3) and was alcohol-resistant bacilli negative. Trans-sphenoidal surgery with biopsy showed inflammation was caused by infection with Aspergillus fumigatus. We initiated use of parenteral amphotericin B, but his condition worsened. He underwent another surgery to implant a reservoir of Ommaya-Hickmann, a subcutaneous catheter. We started liposomal amphotericin B 5 mg/kg in the reservoir on alternate days. He was discharged with a prescription of tegretol and fluconazole.
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This paper presents an overview of the Motherisk Program data on pregnancy outcome and neurodevelopment of children exposed in utero to selected psychoactive drugs. First, the use of cocaine during pregnancy has been associated with increased risk of spontaneous abortions, abruptio placenta, premature labor, and stillbirth. Twenty-three adopted children exposed in utero to cocaine demonstrated an 8-fold increase in risk for microcephaly compared with controls. Global intelligence quotients (IQ) did not differ between the 2 groups, but the cocaine-exposed children achieved significantly lower scores on the Reynell language test. Second, the long-term neurobehavioral effects of fetal alcohol syndrome (FAS) were studied in 384 children to show that alcohol-induced brain insults, which consist of attention and memory deficits together, and poor adaptability and organization are not attenuated with age. Third, the rates of major malformations in children exposed in utero to fluoxetine, tricyclic antidepressants, and nonteratogenic drugs did not differ or exceed the expected rates in the general population. A 2nd phase of this study established the safety of antidepressants during pregnancy by demonstrating that the mean IQ and language scores are comparable in the 3 groups. A level 2 ultrasonography is recommended in cases of in utero exposure to lithium and carbamazepine because of an increased risk of cardiac malformations and spina bifida, respectively.
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The study was performed on 17 patients (14 males + 3 females; mean age 31.8 yrs) treated with carbamazepine (300-1800 mg/day). The control group consisted of six age-matched healthy volunteers. Blood was collected at 8 a.m., 2 p.m., 8 p.m., and 2 a.m. Intergroup analysis was performed with the use of ANOVA Kruskal-Wallis test.
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The aim of this study was to evaluate the impact of polymorphisms in the EPHX1 (c.416A > G, c.337T > C) and CYP3A4*22 genes involved in carbamazepine (CBZ) metabolism and pharmacoresistance among 118 Tunisian patients with epilepsy under maintenance dose of CBZ. These genetic polymorphisms were analyzed by PCR-RFLP. Associations between plasma CBZ concentration, CBZ-E concentration, maintenance doses and metabolic ratio (CBZ-E:CBZ, CBZ-D:CBZ-E) were analyzed with each polymorphism. Both variants of EPHX1 c.416A > G and c.337T > C are significantly associated with higher metabolic ratio CBZ-E:CBZ and seem to decrease the activity of the epoxide hydrolase. The CYP3A4*22 variant allele is significantly associated with lower CBZ-D:CBZ-E ratio and seems also to be associated with less activity of the cytochrome. Our data suggest that certain polymorphisms of metabolizing enzyme genes could influence inter-individual variability of CBZ metabolism.
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The study included 53 patients (age range 3-35 years) who were concomitantly treated with carbamazepine (CBZ) and/or valproic acid (VPA). A total of 70 blood samples corresponding to trough levels were available for analysis. Data were modelled, and the final model was evaluated using NONMEM and auxiliary software tools.
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A total of 40 steady-state serum concentrations from 38 adult and pediatric patients with epilepsy, collected during routine therapeutic drug monitoring, were used for the analysis. To determine the influence of different covariates on the estimate of lamotrigine clearance we built a non-linear mixed-effects one-compartment model with the first order elimination and without absorption.