SEARCH · PubMed Health

Results for “Valproate”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources

PubMed2006

Chronic valproate fails to prevent imipramine-induced behavioural sensitization to the dopamine D2-like receptor agonist quinpirole.

Based on experimental evidence suggesting a relationship between dopamine and mania, we proposed the antidepressant-induced dopaminergic supersensitivity as a model of antidepressant-related mania. We have previously shown the ability of carbamazepine, but not lithium, to prevent this phenomenon. Here we show that sodium valproate (50 mg/kg/day for 3 weeks) fails to prevent imipramine (20 mg/kg/day for 3 weeks)-induced sensitization to the locomotor response to the dopamine D2-like receptor agonist quinpirole (0.15 mg/kg). Since lithium, carbamazepine and valproate are all considered poorly effective in the treatment of antidepressant-related mania, the validity of the proposed model should be disproved by the carbamazepine results, to which, however, a pharmacokinetic mechanism might have concurred.

Analysis of Variance↗

PubMed2003

Effect of valproate on hemostatic function in patients with traumatic brain injury.

OBJECTIVES: To evaluate whether valproate (VPA) resulted in laboratory or clinical evidence of a change in bleeding-related measures associated with VPA therapy in patients sustaining a traumatic brain injury. METHODS: Fibrinogen, platelet count and clot elastic shear modulus using the Thrombelastograph (TEG) coagulation analyzer were measured at baseline, 4, 14, 30, and 180 days post-injury. Clinically significant events, defined as the trigger for requiring a transfusion, were identified and evaluated as to possible treatment effects. RESULTS: Compared to baseline, the platelet count in the VPA groups was decreased on day 4, increased by 100% on day 14, and returned to baseline levels by day 30. Fibrinogen was significantly increased by day 4 and returned to baseline by day 30. The platelet count was correlated with an increase in the maximum amplitude or width of the TEG tracing; a measure of strength of the clot, suggesting that valproate did not alter the clot strength contributed by platelets. None of the clinical events requiring transfusions appeared to be treatment related. CONCLUSIONS: No serious hemostatic adverse events occurred in the trauma patients receiving VPA or phenytoin that could be attributed to treatment.

Adult↗

PubMedDate not supplied

Effects of the combination of valproate and ethosuximide on spike wave discharges in WAG/Rij rats.

OBJECTIVE: We studied the interaction between valproate (VPA) and ethosuximide (ESM) in diminishing the incidence of absence-like spike-wave discharges (SWDs) in the EEG of WAG/Rij rats. METHODS: VPA, ESM, their combination and saline were evaluated in 16 rats. The doses of VPA ranged from 0 to 280 mg/kg and the doses of ESM ranged from 0 to 40 mg/kg. For the drug combination, a fixed weight ratio of 7/1 VPA/ESM was used. The incidence of SWDs in the EEG was determined for the period of 15-75 min after injection and compared to the incidence of SWDs prior to injection. The sigmoid-E(max) equation was fitted to the data. Isobolic analysis, on 50% effect, was used to assess the character of the drug interaction. RESULTS: The parameters for diminishing the incidence of the SWDs were: VPA: ED(50): 121mg/kg; ESM: ED(50): 21.5mg/kg; VPA/ESM: ED(50): 112/16 mg/kg. Isobolic analysis showed that a higher drug load was needed of the combination than of the individual drugs to achieve a 50% reduction of SWDs: factor 1.67; P = 0.012. CONCLUSION: The interaction between valproate and ethosuximide was shown to be infra-additive in diminishing the incidence of SWDs in WAG/Rij rats.

Action Potentials↗

PubMed2004

Effects of lithium and valproate on agonist-induced platelet intracellular calcium mobilization: relevance to myosin light chain kinase.

Serotonin (5-HT)- or thrombin-stimulated platelet intracellular calcium (Ca) mobilization has been reported to be enhanced in patients with bipolar disorders. However, the mechanism of this enhancement is unknown. As a preliminary study, the authors examined the effects of a myosin light chain kinase (MLCK) inhibitor, 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9), and two drugs that are mainstays of treatment for bipolar disorder, lithium and valproate, on 5-HT- or thrombin-induced Ca increase in the platelets of normal subjects. When preincubated with 30 microM ML-9, Ca responses to both agonists were enhanced. Valproate showed a dose-dependent attenuation of agonist-induced intracellular Ca rise, both in the absence and presence of ML-9. Although lithium alone had no significant effect on the Ca increase, a high concentration of lithium significantly decreased Ca mobilization only in the presence of ML-9. These results suggest that the enhanced Ca response observed in bipolar disorder might be relevant to decreased function of MLCK and that the mechanism of action of lithium may include a compensatory effect on MLCK modulation.

Adult↗

PubMed2005

A systematic review of treatment of typical absence seizures in children and adolescents with ethosuximide, sodium valproate or lamotrigine.

PURPOSE: To evaluate the role of ethosuximide, sodium valproate and lamotrigine in children and adolescents with typical absence seizures (AS). METHODS: A systematic review of randomized controlled trials that included children or adolescents with typical absence seizures who received treatment with ethosuximide, sodium valproate or lamotrigine. RESULTS: Four RCTs fulfilled the inclusion criteria. Due to the heterogeneity of the studies the results could not be pooled in a meta-analysis. CONCLUSIONS: We found no reliable evidence to inform clinical practice. The design of further trials should be pragmatic and compare one drug with another.

Anticonvulsants↗

PubMed2005

Intravenous valproate as an innovative therapy in seizure emergency situations including status epilepticus--experience in 102 adult patients.

PURPOSE: The emergency treatment of seizures is an important practical issue, in particular the therapy of status epilepticus. Antiepileptic drugs for this condition should be easy to use, show rapid action, have a long-lasting antiepileptic effect, and have minimal cardiopulmonary and other side-effects. Unfortunately, none of the presently available medications such as phenytoin and barbiturates seems to have all of these four properties. Intravenous valproate became available some years ago and first experiences show promising safety data and efficacy results. METHODS: We report a series of 102 adult patients who received standardized high dosage intravenous valproate in various emergency situations, including status epilepticus. The therapeutic goal was persistent seizure control, defined as successful interruption of clinical seizure activity within less than 15 min, followed by seizure freedom during intravenous therapy for at least 12h. All side effects were documented. RESULTS: In 83/97 patients (85.6%) the therapeutic goal was achieved. Serious side effects were not documented in any patient. In particular there was no evidence of sedation, cardiorespiratory disturbances and hypotension as often seen in barbiturates and phenytoin. Mild side effects occurred in seven cases (6.9%). CONCLUSIONS: The intravenous application of VPA seems to be an easy-to-use, safe and efficient formulation as an alternative to phenytoin in all seizure emergency situations including status epilepticus. Further controlled comparison studies have to be performed in the future.

Adolescent↗

PubMed2005

Visual function in epilepsy patients treated with initial valproate monotherapy.

PURPOSE: To investigate whether initial valproate (VPA) monotherapy for the treatment of epilepsy causes visual field defects and visual dysfunction. METHODS: In a cross-sectional study, visual fields were examined with the kinetic Goldmann and automated Humphrey perimeters, contrast sensitivity function with the Pelli-Robson letter chart and colour vision with the Standard Pseudoisochromatic Plates Part 2 (SPP 2) and Farnsworth-Munsell 100 Hue test (FM 100) in eighteen epilepsy patients (aged 18--50 years, 30.2.+/-10 years, mean+/-S.D.) treated with initial valproate monotherapy for 2--20 years (8.4+/-5.1 years). RESULTS: None had vigabatrin-type, concentric visual field defect with the kinetic Goldmann or automated Humphrey perimetries. In the Humphrey perimetry, the mean deviation for the group was within normal limits varying from -2.53 to 0.59 dB (-0.74+/-0.80 dB) in the right eye and from -2.66 to 0.67 dB (-0.78+/-0.82 dB) in the left eye. In the FM 100 test, acquired colour vision deficiency was found in two out of 18 patients (11%, 95% CI: 0--25%). However, the mean total error score was lower in the patient group than in the control group. All patients had normal contrast sensitivity function. CONCLUSIONS: The use of VPA in the treatment of epilepsy is not associated with visual field defects similar to vigabatrin, but may induce abnormalities in colour vision.

Adult↗

PubMed2006

Capillary microscopy and hemorheology in children during antiepileptic monotherapy with carbamazepine and valproate.

The interactions of epilepsy and antiepileptic therapy an one hand and cardiovascular system on the other hand are multiple and complex. Antiepileptic drugs (AEDs) cause alterations of serum lipids and of the fatty acid composition of the membranes. Homocystein, known to induce vascular endothelial damage was found to be elevated in patients on valproate (VPA) and carbamazepine (CBZ) therapy. Marked coronary artherosclerosis and myocardial infarction may already occur in children treated with CBZ. Community based studies corroborated a higher incidence of myocardial infarction, peripheral vascular diseases hypercholesterinemia, left ventricle hypertrophy and stroke in patients with epilepsy. In this context, we wanted to elevate changes of microcirculation related to AEDs commonly prescribed such as VPA and CBZ. Capillary microscopy is a non-invasive technique for measuring the velocity of red blood cells and for determining nutritional blood flow in the capillaries of the skin. It can easily be performed in children. The aim of this study was to look for possible effects an antiepileptic monotherapy with carbamazepine or valproate has on the peripheral microcirculation in epileptic children. We were able to examine 14 children with CBZ and 24 children with VPA, recruited in our neuropediatric Unit. The results were compared to normative values, determined in former analyses of 207 healthy children. We found significant differences in capillary density, tortuous index of the capillaries, capillary diameter and flow rate of erythrocytes for both antiepileptic drugs. Additionally, there were changes in plasma viscosity and the aggregation of erythrocytes. These microcapillary effects could be of special interest in the relationship of a long-term antiepileptic therapy and the development of vascular diseases. We suggest that the influence of AEDs on microcirculation should also be considered in further studies on cardiovascular changes in patients with antiepileptic long-term medication.

Adolescent↗

PubMed2003

Compliance and satisfaction with switching from an immediate-release to sustained-release formulation of valproate in people with epilepsy.

OBJECTIVE: The goal of our work was to assess compliance and patient satisfaction with switching from sodium valproate to Depakine Chrono in patients with epilepsy. METHODS: Clinical, demographic, and behavioral details assessing compliance and satisfaction were collected using self-completion questionnaires at the time of inclusion in the study and 3 months after the inclusion day. RESULTS: Data were collected from 2031 respondents from eight European countries. There were significant differences between time 1 and time 2 of the study in seizure frequency, reported side effects, compliance, and patient satisfaction. CONCLUSION: Findings suggest that switching from sodium valproate to Depakine Chrono results in an increase in seizure-free rates, a reduction in reported side effects, an improvement in the level of compliance, and a modest improvement in patient satisfaction.

Adaptation, Psychological↗

PubMed2003

Lamotrigine monotherapy compared with carbamazepine, phenytoin, or valproate monotherapy in patients with epilepsy.

OBJECTIVE: This open-label study evaluated the efficacy and tolerability of lamotrigine monotherapy compared with monotherapy with conventional antiepileptic drugs in patients converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. METHODS: This study was conducted in 26 neurology clinics and epilepsy centers throughout the United States. The study enrolled 115 patients with epilepsy converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. Patients were randomized 1:1 to receive 24 weeks of lamotrigine monotherapy or monotherapy with a conventional antiepileptic drug (carbamazepine, phenytoin, or valproate based on physician's choice). Patients were converted during an </=8-week Escalation/Taper Phase from their prestudy antiepileptic drug (carbamazepine, phenytoin, or valproate) to lamotrigine via a protocol-specified dosing algorithm or to conventional therapy via standard dosing guidelines. After monotherapy was achieved, patients continued in the study for a 24-week Maintenance Phase. RESULTS: More lamotrigine patients (65%) than conventional therapy patients (57%) completed the 24-week Maintenance Phase (primary efficacy endpoint). The mean time to withdrawal from the study was 175 days (SD=83.1) for lamotrigine patients compared with 156 days (SD=80.7) for conventional therapy patients. Adverse events, the most common reason for discontinuing the Maintenance Phase, accounted for 16% of withdrawals among lamotrigine patients compared with 26% of withdrawals among conventional therapy patients. The mean reduction in seizure frequency was 53% (SD=55.1) for patients using lamotrigine compared with 32% (SD=149.9) for patients using conventional therapy. Humanistic measures including investigator global assessment, the patient self-assessment, and QOLIE-31 scores show that lamotrigine monotherapy was perceived by both physicians and patients to have benefits over monotherapy with conventional antiepileptic drugs. CONCLUSIONS: Converting from monotherapy with a less effective or poorly tolerated conventional antiepileptic drug to monotherapy with lamotrigine is associated with better clinical and humanistic outcomes than converting to an alternative conventional antiepileptic drug.

Adolescent↗

PubMed2006

Insulin-related metabolic changes during treatment with valproate in patients with epilepsy.

Weight gain is a known side effect of valproate (VPA) therapy, which is associated with hyperinsulinemia and polycystic ovary-like syndrome and unfavorable lipid changes in women. Hyperinsulinemia has also been observed in male and lean subjects as well. Hyperinsulinemia is associated with several health risks, such as cardiovascular diseases and the metabolic syndrome. The purpose of this study was to evaluate whether VPA-related hyperinsulinemia is associated with other metabolic changes and whether there is any association between weight gain, other adverse effects related to VPA, and the metabolic syndrome. Fifty-one patients under VPA monotherapy and 45 healthy control subjects participated in the study. They were interviewed and clinically examined, and, after an overnight fast, blood samples were taken to evaluate fasting serum insulin, lipid, free fatty acid, and uric acid levels. Incidence of the metabolic syndrome was determined as well. Compared with control subjects, VPA-treated patients had higher circulating insulin concentrations relative to body mass index, higher uric acid and triglyceride levels, and lower high-density lipoprotein cholesterol concentrations. There was no significant difference in the frequency of the metabolic syndrome between the VPA-treated patient group and the control group. In conclusion, valproate therapy, especially if started at a young age, is associated with increased circulating insulin concentrations relative to body mass index, indicating that the high insulin levels are not a consequence of obesity. Although the frequency of the metabolic syndrome did not differ between VPA-treated patients and control subjects, VPA-treated patients had higher concentrations of triglycerides and uric acid and lower levels of high-density lipoprotein cholesterol than control subjects.

Adult↗

PubMed2003

Valproate attenuates hyperactive and perseverative behaviors in mutant mice with a dysregulated dopamine system.

BACKGROUND: Dopamine transporter (DAT) knockdown (KD) mice, with approximately 90% loss of expression of the DAT, allow for the examination of the behavioral consequences of a chronically dysregulated dopamine system. The DAT KD mice have hyperdopaminergic tone, are hyperactive, and show impaired response inhibition in a number of paradigms. We hypothesized that the DAT KD mice would also display deficits in prepulse inhibition (PPI) and would be perseverative in their locomotor behavior. METHODS: Basal levels of PPI and patterns of locomotor behavior were measured in two cohorts of DAT KD mice. In addition, measurements of locomotor behavior were recorded after pretreatment with 100 mg/kg valproate in both DAT KD and wildtype mice. RESULTS: The DAT KD mice were hyperactive and displayed perseverative motor behavior but had normal levels of PPI. The clinically effective antimania drug valproate significantly attenuated the hyperactivity and perseverative locomotor behavior in the DAT KD mice and had no effect in control mice. CONCLUSIONS: The DAT KD mice appear to provide a model of some aspects of manic behavior. With limited models of bipolar disorder, the DAT KD mice might provide a vehicle to screen for new psychiatric therapies to treat mania and its related symptoms.

Animals↗

PubMed1993

Reversible Fanconi syndrome associated with valproate therapy.

Two children with developmental delay and seizure disorders had Fanconi syndrome associated with valproate therapy. Both recovered normal proximal tubular function within 4 months of discontinuing valproate therapy.

Child↗

PubMed1992

Comparison of sprinkle versus syrup formulations of valproate for bioavailability, tolerance, and preference.

We compared a new coated-particle formulation of valproate (Depakote Sprinkle) capsules with valproic acid (Depakene) syrup for bioavailability, side effects, and patient and parent preference. Twelve children with epilepsy, aged 5 to 16 years, participated in this randomized, two-period, crossover study. They were assigned to a 7-day regimen with one formulation and then crossed over to the other; the drug was given every 12 hours. On day 7, blood samples collected during a 12-hour period were analyzed for the presence of valproate. At the study's end, parents and children were asked structured questions regarding formulation preference and adverse events. The extent of absorption from sprinkle equaled that from syrup (relative bioavailability = 1.02), but absorption was slower (time to maximum concentration = 4.2 vs 0.9 hour; p less than 0.01). Fluctuations in serum concentrations were less with sprinkle (34.8% vs 62.3%; p less than 0.01). Sprinkle was preferred by 9 of the 12 parents because of east of administration, and by nine of the children because of improved palatability. We conclude that sprinkle may be substituted for syrup without changing the daily dose. Furthermore, sprinkle, because of its prolonged absorption, may be given every 12 hours to children receiving monotherapy. Compliance may be enhanced because of the more convenient dosing schedules and the high degree of patient and parent acceptance.

Absorption↗

PubMed1980

Acute liver disease associated with sodium valproate.

Five patients, four of them children, had acute liver disease after treatment with sodium valproate. Three died. The liver disease began 3-6 months after the start of treatment and was often associated with other side-effects of sodium valproate such as thrombocytopenia and hair loss.

Acute Disease↗

PubMed1996

Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy.

BACKGROUND: The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients. We know of only one randomised comparative trial (of two drugs) in newly diagnosed childhood epilepsy. We have undertaken a long-term, prospective, randomised, unmasked, pragmatic trial of the comparative efficacy and toxicity of four standard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy. METHODS: Between 1981 and 1987, 167 children aged 3-16 years, who had had at least two previously untreated tonic-clonic or partial seizures, with or without secondary generalisation, were randomly allocated treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform to standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission. FINDINGS: The overall outcome with all four drugs was good. 20% of children remained free of seizures and 73% had achieved 1-year remission by 3 years of follow-up. We found no significant differences between the drugs for either measure of efficacy at 1, 2, or 3 years of follow-up. The overall frequency of unacceptable side-effects necessitating withdrawal of the randomised drug was 9%. This total included six of the first ten children assigned phenobarbitone; no further children were allocated this drug. Of the other three drugs, phenytoin (9%) was more likely to be withdrawn than carbamazepine (4%) or sodium valproate (4%). INTERPRETATION Our data will inform choice of drug and outcome with four of the standard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children.

Adolescent↗

PubMed2001

Effect of lithium and sodium valproate ions on resting membrane potentials in neurons: an hypothesis.

In an attempt to understand the therapeutic effects of lithium and sodium valproate in stabilizing the moods in manic depressive illness, the well-known Goldman-Hodgkin-Katz (G-H-K) equation is modified to include a fourth ion, such as a lithium ion or a sodium ion. The modified G-H-K equation is used to calculate the resting membrane potential in neurons. These calculations show that the resting membrane potential is depolarized depending upon the relative concentration of the lithium ion and upon its relative permeability. These calculations suggest that the resting membrane potential may be hyperpolarized in bipolar patients before treatment, and that the lithium ion perhaps depolarizes the resting membrane potential back to the normal level. They further support the prevailing hypothesis that manic-depressive illness may be caused by the hyperpolarization of the resting membrane potential, which, in turn, may be caused by the changes in ionic conductance (permeability) of the membranes. Sodium ions in sodium valproate do not significantly affect the resting membrane potential since they do not significantly change in the serum.

Bipolar Disorder↗

PubMed1999

Cyclic AMP responsive element binding protein phosphorylation and DNA binding is decreased by chronic lithium but not valproate treatment of SH-SY5Y neuroblastoma cells.

Mood stabilizing drugs decrease central nervous system cyclic AMP signaling. We report here that chronic, but not acute treatment with lithium chloride in human neuroblastoma SH-SY5Y cells, inhibits phosphorylation of cyclic AMP responsive element binding protein and cyclic AMP responsive element DNA binding induced by the adenylyl cyclase activator forskolin, but has no effect on constitutive expression of cyclic AMP responsive element binding protein. These results are consistent with an effect of lithium to blunt the cyclic AMP signal transduction pathway. Such an effect is not shared by the other commonly prescribed mood stabilizer, sodium valproate. Our results suggest that cyclic AMP responsive element binding protein regulated gene expression may be relevant to the long-term prophylactic effect of lithium. Furthermore, sodium valproate, which is also effective in bipolar disorder, would appear to act on other pathways to bring about its therapeutic effects.

Adenylyl Cyclases↗