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At least 883 records · Page 49Linked to original sources

PubMed1984

Sodium valproate and cognitive function.

The literature concerning the effects of sodium valproate on cognitive function was reviewed, including both volunteer and patient studies. Two were reported from the National Hospital--one a double-blind crossover investigation against placebo in volunteers, and the other in patients on monotherapy. It was concluded that sodium valproate has minimal adverse effects, although those that are seen are probably dose related. It has less of an effect on cognitive function than some of the other commonly used anticonvulsants.

Adolescent↗

PubMedDate not supplied

The effect of sodium valproate on sleep, reaction times, and visual evoked potential in normal subjects.

The effect of enteric-coated sodium valproate on 10 normal volunteer subjects was evaluated using simple reaction times, the visual evoked potential (VEP), and EEG sleep recording. Placebo, low-drug (500 mg), high-drug (1,000 mg), and withdrawal conditions were investigated. No significant treatment effect was found for simple reaction time nor was there any significant effect on either the latency or the amplitude of the VEP. Sleep recordings were analysed visually and also using an automated technique consisting of simple period analysis. The automated sleep results suggested that there was a decrease in rapid eye movement activity and an increase in delta activity under the high-drug condition. The visually analysed data did not reach significance, although they followed the same trends as those analysed automatically. It is possible that the automated results reflect an EEG frequency change rather than a change in the sleep cycle itself caused by treatment with sodium valproate.

Adult↗

PubMedDate not supplied

Effect of sodium valproate on psychomotor performance in children as a function of dose, fluctuations in concentration, and diagnosis.

Forty-six children receiving sodium valproate monotherapy, and with well-controlled seizures, were tested three times, at weekly intervals in the morning, on an extensive battery of psychomotor tests. The first session was a practice session to minimize subsequent practice effects. On one of the remaining 2 test days, morning medication was delayed until after testing (low concentration condition), whereas sodium valproate was given before testing on the alternate session (high concentration day). The data were analyzed for the effects of diagnosis (partial vs. generalized epilepsy), dose (above or below 20 mg/kg/day), and time of medication (low and high drug concentration days). Four variables discriminated between the diagnostic groups, all favoring children with generalized epilepsy. Another four measures were significantly associated with dose, with those on lower doses performing at a superior level. Time of medication had virtually no effect on performance, however. The findings were related to previous diagnostic and dosage research. Although a deterioration in performance at higher doses appears to be consistent with other dosage research, the absence of an effect due to time of medication suggests that performance does not fluctuate between drug administrations.

Adolescent↗

PubMedDate not supplied

Dose-dependent pharmacokinetics of valproate in guinea pigs of different ages.

The dose-dependence of sodium valproate (VPA) pharmacokinetics in relation to age was studied using guinea pigs. Sodium valproate in doses of 20, 200, and 600 mg/kg was administered by rapid intravenous infusion to male guinea pigs 3, 21, and 42 days old. Serum levels of VPA were determined by gas chromatography. Pharmacokinetic parameters were calculated based upon a two-compartment model. The area under the plasma concentration-time curve (AUC) increased out of proportion at the 600 mg/kg dose level in all groups. Other pharmacokinetic changes were as follows: in 3-day-old guinea pigs, the slow disposition rate constant (beta), the elimination rate constant from central compartment (K10), and the total clearance (Clt) were significantly decreased and the beta phase half-life (t 1/2) and the volume of central compartment (V1) were significantly increased at the 600 mg/kg dose level. In 21-day-old guinea pigs, beta and K10 were significantly decreased and t1/2 and V1 were significantly increased at doses of both 200 mg/kg and 600 mg/kg. In 42-day-old guinea pigs, however, only V1 and the volume of distribution at steady-state (Vss) showed significant increase after increasing doses. The extraction ratio (E) and the clearance of unbound drug (Clu), which were calculated based on unbound plasma levels, indicate that the dose-dependent kinetics of VPA are probably due to saturation of metabolism and that the metabolic capacity for VPA in the newborn group is the smallest among all groups.

Aging↗

PubMed1987

Valproate monotherapy in the management of generalized and partial seizures.

For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.

Clinical Trials as Topic↗

PubMed2001

Hyperammonemia and coma without hepatic dysfunction induced by valproate therapy.

The authors report a case of a 41-year-old mentally disabled man with bipolar disorder who presented to the emergency department with altered mental status. He was found to have a significantly elevated ammonia level (377 microM/L) with no signs of hepatic insufficiency. His coma and hyperammonemia were attributed to his chronic valproate therapy. This patient had the highest serum ammonia level ever reported with a therapeutic valproate level in the absence of any other anticonvulsant therapy, metabolic abnormality, or hepatic dysfunction. The authors discuss this case and review the current literature on hyperammonemia in valproic acid therapy and the use of L-carnitine in these patients.

Adult↗

PubMed1983

Serum thyroid hormones and blood folic acid during monotherapy with carbamazepine or valproate. A controlled study.

Studies investigating the influence of antiepileptic drugs on thyroid hormones usually have compared patients chronically treated with antiepileptic drugs to controls. To date, this type of designs has produced divergent results both with regard to individual drugs and individual thyroid hormones. The present study comprised 31 patients with newly diagnosed epilepsy, commencing treatment with either carbamazepine or valproate. T3, T4, FT4, FT3, rT3, TSH, T3 resin uptake and blood folic acid, were determined before and during antiepileptic monotherapy, thus making the patient his own control. During treatment with carbamazepine, a significant decrease in T4, FT4, FT3, rT3 and TBG was observed. Valproate caused a decrease in T4, FT4 and T3. Neither of the drugs caused any changes in blood folic acid concentrations or persistent increases in the TSH values. None of the patients developed overt symptoms of hypothyreoidism. Conceivable mechanisms underlying these hormonal changes are reviewed.

Adolescent↗

PubMed1984

Weight gain during treatment with valproate.

An analysis was made of weight changes during treatment with valproate in 63 adult epileptic patients. 36 patients (57%) gained more than 4 kg in weight during treatment, while 27 patients (43%) were stable in weight with weight changes of less than +/- 4 kg. There were no significant differences between weight gainers and weight-stable patients with regard to age, sex, pretreatment overweight, duration of treatment, dosage or serum levels of valproate. From structured patient interviews, it appeared that the 2 groups of patients differed only insignificantly with regard to appetite, thirst and familial predispositions to obesity and diabetes. Consequently, no factors predictive for weight gain could be outlined. Presumable pathogenic mechanisms of importance are discussed.

Adult↗

PubMed1984

The effects of carbamazepine and valproate on folate metabolism in man.

The effect of carbamazepine and valproate treatment on folate metabolism was studied in 11 epileptic patients. The absorption of folic acid and of Pteroyl-gamma-L-glutamyl-gamma-L-glutamyl-L-glutamic acid, a synthetic substrate for intestinal folate deconjugase , was measured prior to and after 2 months of antiepileptic therapy with either carbamazepine (5 cases) or valproate (6 cases). After 2 months' treatment, the area under plasma concentration versus time curve was significantly decreased and t-max (time when maximal plasma concentration is obtained) was significantly prolonged. No inhibition of intestinal folate deconjugation was observed and the liver metabolism of folic acid was found to be unaffected by the treatment. These findings are interpreted as an inhibition of intestinal folic acid absorption caused by the antiepileptic therapy.

Adolescent↗

PubMed1997

Auditory event related potentials in patients with epilepsy on sodium valproate monotherapy.

OBJECTIVES: The effects of antiepileptic drugs on event related potentials (ERPs) have been studied, but with contradictory results. In this study we examine the effect of sodium valproate (VPA) on ERPs in patients with epilepsy. MATERIALS AND METHODS: Auditory event related potentials were recorded in 40 patients with idiopathic generalized epilepsy, 20 on monotherapy with sodium valproate (VPA), 20 on monotherapy with carbamazepine and 20 age and sex matched controls. All subjects performed a simple auditory discrimination task in which a target tone was presented on 20% of the trials. RESULTS: Mean P3 latency of the VPA group was significantly prolonged but not in carbamazepine group and healthy controls. CONCLUSION: We conclude that VPA monotherapy has an effect on P300 latency in patients with epilepsy. This difference might be attributed to effects of treatment with VPA and may clarify in the future the mechanism of P300.

Adult↗

PubMed2006

Valproate-induced hyperammonemic encephalopathy.

Valproate-induced hyperammonemic encephalopathy (VHE) is an unusual complication characterized by a decreasing level of consciousness, focal neurological deficits, cognitive slowing, vomiting, drowsiness, and lethargy. We have thoroughly reviewed the predisposing factors and their screening, the biochemical and physiopathological mechanisms involved, the different treatments described, and those that are being investigated. Etiopathogenesis is not completely understood, although hyperammonemia has been postulated as the main cause of the clinical syndrome. The increase in serum ammonium level is due to several mechanisms, the most important one appearing to be the inhibition of carbamoylphosphate synthetase-I, the enzyme that begins the urea cycle. Polytherapy with several drugs, such as phenobarbital and topiramate, seems to contribute to hyperammonemia. Hyperammonemia leads to an increase in the glutamine level in the brain, which produces astrocyte swelling and cerebral edema. There are several studies that suggest that treatment with supplements of carnitine can lead to an early favorable clinical response due to the probable carnitine deficiency induced by a valproate (VPA) treatment. Development of the progressive confusional syndrome, associated with an increase in seizure frequency after VPA treatment onset, obliges us to rule out VHE by screening for blood ammonium levels and the existence of urea cycle enzyme deficiency, such as ornithine carbamoyltransferase deficiency. Electroencephalography (EEG) is characterized by signs of severe encephalopathy with continuous generalized slowing, a predominance of theta and delta activity, occasional bursts of frontal intermittent rhythmic delta activity, and triphasic waves. These EEG findings, as well as clinical manifestations and hyperammonemia, tend to normalize after VPA withdrawal.

Anticonvulsants↗

PubMed1985

Valproate as psychotropic agent. Interactions and adverse cerebral reactions.

Recent data stress the psychotropic actions of valproate in schizo-affective disorder. Four patients are reported presenting an altered state of consciousness and prominent EEG dysfunction following combined valproate/neuroleptic drug treatment. Similar cerebral reactions have been reported in anti-epileptic poly- and monotherapy, and the pathogenetic considerations are discussed. Further investigations of the interactions of valproate with other psychotropic agents are highly mandatory.

Adult↗

PubMed1991

The extracellular concentration of the anti-epileptic drug valproate in the rat brain as determined with microdialysis and an automated HPLC procedure.

The cellular and extracellular brain concentration of valproic acid in freely moving rats has been estimated after intravenous injection of sodium valproate. Some rats were provided with a stereotaxically implanted dialysis probe in the striatum and a cannula in the heart through which the drug was injected and which allowed regular removal of blood. In other rats tissue levels of valproic acid were determined 5 and 90 min after drug injection. Valproic acid was determined by an automated precolumn derivatization procedure followed by HPLC separation and fluorimetric detection. Extracellular concentration was proportional to the blood concentration at every time interval, indicating rapid exchange of the drug between the two compartments. About 50% of the striatal content of valproate was in extracellular space. The experiments demonstrated the usefulness of microdialysis to estimate both the extracellular concentration and the average cellular drug levels, provided a sensitive analysis procedure is available.

Animals↗

PubMed1988

Randomised controlled trials of phenobarbitone and valproate in febrile convulsions.

Results from British trials of phenobarbitone and valproate for the prophylactic treatment of febrile convulsions were pooled and analysed on an intention to treat basis. The overall odds ratio for phenobarbitone was 0.8 and for valproate 1.42. Neither result was significant. Neither treatment can be recommended in the light of experience.

Child↗

PubMed1974

Sodium valproate in treatment of epilepsy.

Sodium valproate has a simple chemical structure unlike other anticonvulsants. It has been given to 63 patients with various types of epilepsy whose attacks were frequent and of whom 40 had failed to respond to other anticonvulsants. Fits stopped completely in 27 patients (43%) and 14 (22%) showed a reduction of attacks by more than 50%. The best results were in patients with absences (typical and atypical) associated with spike and wave discharges on the electroencephalogram. Myoclonic epilepsies responded well and improvement occurred with tonic-clonic seizures and focal motor fits. There was little or no improvement in temporal lobe epilepsy. Sodium valproate given alone did not cause unwanted effects but it potentiated many other anticonvulsants. An unusual side effect was temporary hair loss. A number of patients became more alert, school performances improved, and the management of subnormal patients became easier.

Adolescent↗

PubMed1987

Fetal valproate syndrome: is there a recognisable phenotype?

Four infants who were exposed to sodium valproate or valproic acid during pregnancy are described. Common facial features in the three surviving infants include epicanthic folds, a flat nasal bridge, a broad nasal base, anteverted nostrils, a shallow philtrum, and a thin upper lip with a thick lower lip. Ridging of the metopic suture, congenital heart defect, postaxial polydactyly, and hypospadias were additional features in individual cases. In agreement with previous authors, we feel that there is a distinctive 'fetal valproate' phenotype.

Abnormalities, Drug-Induced↗

PubMed1978

Sodium valproate in the treatment of levodopa-induced dyskinesia.

The effect of sodium valproate 1200 mg daily on the disability of Parkinsonism and on levodopa-induced dyskinesia was assessed in a double-blind crossover trial with matched placebo in 12 patients with Parkinson's disease. No objective change in the severity of Parkinsonism or dyskinesias was noted. However, six out of nine patients who completed the trial noted a slight to moderate improvement in their dyskinesias with no change in their Parkinsonism. Excess salivation improved in four subjects on sodium valproate.

Clinical Trials as Topic↗

PubMed1982

A comparison of phenytoin and valproate in previously untreated adult epileptic patients.

Eighty-eight patients with the onset of epilepsy in adult life were randomly allocated to treatment with sodium valproate (600 mg/day), or phenytoin (300 mg/day), and followed up for at least 12 months. Both drugs were highly effective in the control of tonic-clonic seizures, irrespective of whether they were accompanied by focal features, but were markedly less effective in the control of partial seizures. Two patients exhibited acute allergic reactions to phenytoin. No significant differences have yet emerged in the efficacy of the two drugs, and valproate may be considered as a "fist-line" anticonvulsant in the treatment of adult onset epilepsy.

Adolescent↗