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Results for “Valproate”

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PubMed1996

Sodium valproate in severe migraine and tension-type headache: an open study of long-term efficacy and correlation with blood levels.

We performed an open prospective study of the prophylactic efficacy of sodium valproate in 56 patients among which 35 migraineurs, 7 chronic tension-type headache patients and 14 patients with combined headaches. We compared the mean number of headache days per month during a one-month-baseline period without prophylactic treatment and during the last month of a 6-month-treatment course. Among secondary parameters, we assessed headache intensity, adverse experiences and we measured valproate blood levels after one and after six months of treatment. Sixty percent of migraineurs had a 75% or more improvement in the number of headache days under sodium valproate, most of the remaining attacks being less severe. There was no significant improvement in chronic tension-type headache patients and only a mild effect in patients with combined headaches, almost exclusively on the migraine component. Thirty percent of patients reported adverse effects of which none was serious: there were 3 drop-outs. We found a moderate, but statistically significant, correlation between efficacy and blood levels of sodium valproate.

Adult↗

PubMed1996

Effect of retinoic acid and valproate on sea urchin development.

The effect of valproate and retinoic acid on Paracentrotus lividus development and fertilization is reported. Retinoic acid at concentrations between 5 microM and 7 microM causes severe disturbance of development and at 10 microM complete embryo degeneration if added in the period from fertilization on. Concentrations up to 7 microM are uneffective if retinoic acid addition is started 16 h after fertilization. Valproate at concentrations between 1 mM and 5 mM causes severe disturbances of development if added from 5 min after fertilization on. Concentrations of 20 mM are lethal to all embryos. If the drug is added 16 h after fertilization no effect is observed up to the concentration of 10 mM. The effect of valproate is specific, because its isomere 2-en at 10 mM has very little effect on development. Both drugs affect fertilization only at higher concentrations: more than 1 microM for retinoic acid and more than 10 mM for valproate.

Animals↗

PubMed1998

[Therapy of bipolar affective illnesses with valproate. A review of the literature].

This paper gives an overall review of the literature since 1980 on the use of valproate in bipolar affective disorders. Randomised comparative studies definitely demonstrate that valproate proves superior in comparison with placebo and equivalent in comparison with lithium in the treatment of acute manic episodes. A series of open studies indicates a reduction in frequency and intensity of manic and depressive episodes with the long-term administration of valproate suggesting efficaciousness in the prophylaxis of bipolar affective disorders. Details on dosage, side effects and potential interactions with this group of patients are presented. Valproate constitutes a further valuable and well tolerated alternative to lithium, antipsychotic agents and carbamazepine not only in acute therapy of manic episodes but also in prophylactic treatment of patients with bipolar psychosis.

Anticonvulsants↗

PubMed1982

Valproate and clonazepam in the treatment of severe progressive myoclonus epilepsy.

Twenty-six adults with severe progressive myoclonus epilepsy (PME) were admitted to a long-term prospective clinical study; 19 were followed up for six years. The previous medication, phenytoin sodium and other antiepileptic drugs, was changed to valproate sodium (Deprakine [Finland]; Depakene Syrup, comparable US product), clonazepam (Clonopin), and phenobarbital, and the patients' conditions improved. After six years of follow-up, the favorable result continued. The mean plasma concentration in 26 patients after four months of follow-up was 27.8 +/- 6.9 mg/L for valproate, 0.053 +/- 0.025 mg/L for clonazepam, and 19.2 +/- 7.9 mg/L for phenobarbital. The clinical response was not in accordance with the plasma drug concentrations when the data of the whole population were statistically analyzed. The classification of disability of patients with PME into five degrees was useful. The longlasting favorable result suggests that the combination of valproate, clonazepam, and phenobarbital is the most effective therapy for severe PME.

Adolescent↗

PubMed1990

Valproate-induced coma with ketosis and carnitine insufficiency.

We observed two patients who developed coma following administration of valproate in dosages of 32 to 40 mg/kg per day. Valproate levels were within the therapeutic range, and results of liver function studies were normal. Both patients had ketosis and adipic aciduria. Plasma free carnitine levels were decreased during coma and after recovery. One patient excreted ethylmalonic acid, butyrylcarnitine, and glutarylcarnitine during and after resolution of coma, suggesting a multiple acyl coenzyme A dehydrogenation defect. Low serum carnitine levels may predispose patients to development of altered consciousness when treated with valproate.

Acids↗

PubMed2005

Valproate embryopathy: clinical and cognitive profile in 5 siblings.

Valproate embryopathy is a well recognized syndrome caused by prenatal exposure to the anticonvulsant valproic acid (Depakote). We report five half-siblings with the same mother (four different fathers) who all have valproate embryopathy. Valproic acid was the sole anticonvulsant in all five pregnancies, with doses ranging from 500 to 2,000 mg per day. All children were examined by a clinical geneticist and developmental pediatrician, and had formal developmental testing. Mean birth weight at term was 2,900 g (range: 2,400-3,400 g). Common features in the five children included: flat, broad nasal bridge (5/5), hypoplastic midface (4/5), apparent hypertelorism/telecanthus (4/5), smooth philtrum (4/5), thin upper lip (5/5), long thin tapering fingers (4/5), hypoplastic 5th toenails (2/5), and irregularly placed toes (2/5). Less frequent features were micro/brachycephaly (2/5), cleft palate (1/5), duplication cyst of small intestine (1/5), and hemangioma (1/5). None had neural tube defect. Neuropsychologic testing of the three children older than 4 years of age showed cognitive ability in the low normal or borderline range (mean IQ = 83; range: 75-86), with significantly lower scores in adaptive behavior and motor skills. Study of this family offers insight into the potentially high risk of valproate embryopathy in exposed pregnancies, and affords a unique opportunity to study the variability of expression and cognitive profile of the syndrome within one family.

Abnormalities, Drug-Induced↗

PubMed2004

Valproate therapy and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease was defined recently as another symptom of insulin resistance. Continuous therapy with valproate can result in increased body weight and insulin resistance, but no data are yet available on a possible relationship between valproate and nonalcoholic fatty liver disease. We here demonstrate in abdominal ultrasound investigations that characteristics of fatty liver disease were present in 61% of valproate-treated patients as compared with 23% receiving carbamazepine therapy.

Adolescent↗

PubMed1979

Acute intoxication with sodium valproate.

Two epileptic patients developed an acute toxic encephalopathy consisting of altered behavior, deteriorating seizure control, and confusion while taking sodium valproate alone. Serum valproate levels were greater than 100 microgram/ml in both. Toxic symptoms resolved when the dose of valproate was reduced, with a consequent fall in serum concentration of the drug.

Acute Disease↗

PubMed1998

Hyponatremia due to sodium valproate.

We describe a 50-year-old male patient with hyponatremia (serum sodium level, 128 mEq/L) discovered during routine follow-up for Henoch-Schönlein nephritis. The patient was known to have a generalized idiopathic epilepsy and was on 2,000 mg/day of sodium valproate. After exclusion of other causes such as hypothyroidism and adrenal insufficiency, we considered sodium valproate as the cause of the hyponatremia. Repeated water loading tests performed at different dosages of this drug confirmed that the ability to excrete water was reduced in a dose dependent manner. We conclude that sodium valproate can cause an SIADH-like syndrome with hyponatremia and that serum sodium levels have to be monitored during treatment with high dosages of this drug.

Anticonvulsants↗

PubMed1983

The toxicity of metabolites of sodium valproate in cultured hepatocytes.

Sodium valproate is hepatotoxic in both humans and rat hepatocytes. The toxicity is dose related and frequently associated with simultaneous ingestion of drugs which induce the drug metabolizing system. For these reasons, metabolites of sodium valproate were tested for toxicity using rat hepatocyte cultures. The sodium salts of three metabolites, 2-propylpent-4-enoate, 4-hydroxyvalproate, and perhaps 5-hydroxyvalproate, were toxic in this system. In addition, 2-propylpent-4-enoate was toxic in a dose-related fashion. All are omega and omega-1 oxidation products in the microsome-mediated pathway of valproate metabolism.

Animals↗

PubMedDate not supplied

An update on sodium valproate.

Sodium valproate has been in clinical use for the treatment of epilepsy in Great Britain since 1973 and in the United States since 1978. It is chemically quite different from the existing antiepileptic drugs. Although most authorities concentrate on its modification of GABAergic inhibitory transmission in the central nervous system, its mechanism of action remains obscure. It has been shown to be an effective antiepileptic drug in a wide variety of seizure types, but clinically, its major use to date has been in generalized seizures. It is particularly effective in photosensitive epilepsy and myoclonus. Most adverse reactions to sodium valproate are mild and reversible, but with increasing experience, the drug's rare, idiosyncratic, adverse effects are becoming apparent, particularly hepatotoxicity and teratogenicity. The role of therapeutic drug monitoring in the management of patients taking sodium valproate is controversial.

Anticonvulsants↗

PubMed1986

An assessment of the effects of cyclophosphamide and sodium valproate on the viability of preimplantation mouse embryos using the fluorescein diacetate test.

The fluorescein diacetate test is a measure of both esterase enzyme activity and membrane integrity and it has been shown to be useful in assessing the viability of a variety of cells cultured in vitro, mouse embryos after freezing and thawing, and mouse embryos grown under inadequate culture conditions. In this study, the effects were examined of cyclophosphamide and sodium valproate administered respectively to pregnant inbred CBA mice 60 h after fertilization, on the viability of 84-h blastocysts. Cyclophosphamide 20 and 40 mg/kg bodyweight and sodium valproate 90 mg/kg significantly increased the number of nonviable blastocysts. Cyclophosphamide 4 mg/kg and sodium valproate 23 and 45 mg/kg did not adversely affect blastocyst viability. The intensity of embryo fluorescence correlated well with the subsequent development of the embryos in culture (r = 0.863; p less than 0.001). The test had a sensitivity of 83% and a specificity of 100%. Exposure of embryos to fluorescein diacetate under the conditions of this experiment did not adversely influence the subsequent postimplantation development of 84-h blastocysts cultured in vitro for a further 120 h. These findings suggest that the fluorescein diacetate test is a simple, rapid, and nontoxic procedure that may be useful in assessing the viability of preimplantation embryos after exposure to embryotoxic drugs and chemicals.

Animals↗

PubMed2001

Lamotrigine Monotherapy Improves Depressive Symptoms in Epilepsy: A Double-Blind Comparison with Valproate.

Depressive symptoms are highly prevalent in patients with epilepsy. The antiepileptic drug lamotrigine has been shown to be an effective treatment for the depressive phase of bipolar disorder and to enhance mood and well-being in epilepsy patients. The effects of lamotrigine monotherapy on depressive symptoms in epilepsy have not been evaluated to date in a controlled clinical trial. A recently completed double-blind epilepsy trial comparing the effects of lamotrigine monotherapy and valproate monotherapy on weight change incorporated a battery of standard mood assessments. Mean screening Beck Depression Inventory scores showed that both lamotrigine and valproate groups suffered from mild depression at baseline. Lamotrigine monotherapy was reliably associated with earlier and larger improvements than valproate in mood assessed with the Beck Depression Inventory, the Cornell Dysthymia Rating Scale, and the Profile of Mood States. Considered in the context of other data showing lamotrigine's antidepressant efficacy in bipolar depression, these results suggest that lamotrigine improves mood in mildly depressed patients with epilepsy. Lamotrigine may be particularly useful in treating epilepsy patients with comorbid depression, the most common psychiatric illness in epilepsy.

Journal Article↗

PubMed2001

Treatment of Childhood Idiopathic Language Deterioration with Valproate.

Childhood idiopathic language deterioration is a rare condition in which children lose previously gained language skills. In some children this language deterioration occurs in association with behavioral seizures or EEG epileptiform activity. The effectiveness of antiepileptic drugs in this patient population is not known. Here we retrospectively reviewed records of 57 children with childhood idiopathic language deterioration associated with seizures or epileptiform activity on their EEG who received valproate for the purpose of treating their language impairment. In 22 of the children improvement in language skills was observed. In two children language returned to normal while in the other 20 the improvement was modest. Children who responded to valproate had an earlier age of onset of the aphasia than children who were nonresponders. Seizure type, EEG findings, developmental status, and presence or absence of a frequency-modulated auditory evoked potential were not related to response. This study demonstrates that valproate can be helpful in improving language function in some children with idiopathic language deterioration associated with seizures or epileptiform activity on the EEG.

Journal Article↗

PubMed1988

Prolactin response to sodium valproate in schizophrenics with and without tardive dyskinesia.

Sodium valproate, a GABAergic agent (800 mg), and placebo were administered orally, as a single dose, to nine chronic schizophrenics with tardive dyskinesia (TD), seven chronic schizophrenics without TD and ten healthy controls, according to a double blind design. Blood samples were collected before and after drug administration, to determine plasma prolactin concentrations. Sodium valproate decreased plasma prolactin levels in healthy subjects (P less than 0.001) and in schizophrenic patients with TD (P less than 0.001), but not in chronic schizophrenics without TD. Moreover, in dyskinetic subjects, the maximum per cent decrease of plasma prolactin from basal value was positively correlated to the score of the abnormal involuntary movement scale (r = 0.724, P less than 0.02). Although the neural or biochemical substrate underlying the different responses of plasma prolactin to sodium valproate in schizophrenics with and without TD remains unclear, these results provide the first neuroendocrine evidence able to differentiate dyskinetic subjects from those without TD within a schizophrenic population.

Adult↗

PubMed1995

Interaction between valproate formulation and phenytoin concentrations.

Changes in phenytoin concentrations caused by switching valproate formulations with different absorption rates were retrospectively investigated in eleven epileptic patients receiving treatment with both drugs. Total plasma phenytoin concentrations were measured before and after a standard tablet of valproate was replaced by the same dose as a slow-release tablet. The mean plasma phenytoin level rose significantly from 14.4 to 18.7 micrograms.ml-1. Nine of eleven patients had markedly increased phenytoin levels (by 21 to 72%), and two developed toxic symptoms. The results indicate that changing valproate formulations can cause major alterations in the plasma concentration of co-administered phenytoin.

Adolescent↗

PubMed1985

Distribution of sodium valproate in normal whole blood and in blood from patients with renal or hepatic disease.

Sodium valproate at a concentration of 300 mumol/l in whole blood, partitioned between the red blood cell and plasma to produce a red blood cell/plasma partition ratio of 0.20. Red blood cell uptake was proportional to percent free drug in plasma and uptake was maximal when plasma was replaced by buffer, producing a red blood cell/buffer ratio of 0.87. Reduction of plasma protein binding by plasma dilution, by increasing the total sodium valproate plasma concentration, or by renal or hepatic disease in 24 patients, caused a predictable rise in red blood cell uptake of drug. The red blood cell represented a relatively small compartment for free sodium valproate in blood, however uptake of the drug into this compartment increased considerably in states of reduced plasma protein binding. Because the concentration of drug in the red blood cell reflects free drug concentration in plasma, the red blood cell may serve as an indicator of free drug changes in blood.

Adult↗

PubMed1985

Sodium valproate and brainstem energetics.

The effect of the anticonvulsant sodium valproate on cerebral brainstem energy metabolism has been investigated. Stupor and coma were produced in mice by the intraperitoneal injection of sodium valproate at a dose of 600 mg/kg. Glucose, glycogen, ATP, and phosphocreatine were measured in small tissue samples from the ascending reticular activating system. Levels of all metabolites were either normal or elevated in precoma and comatose mice as compared to controls. These data are consistent with the concept that sodium valproate does not have a primary action through depletion of high energy phosphates.

Adenosine Triphosphate↗