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PubMed2004

Two cases of valproate-induced hyperammonemic encephalopathy without hepatic failure.

We report two children with localization related epilepsies, who presented with somnolence, seizure exacerbation, behavioral alteration, decline in speech and cognitive abilities, and ataxia while being treated with a combination of valproate and topiramate, but had previously tolerated valproate with other antiepileptic drugs. These children had elevated serum ammonia, normal transaminase levels, and generalized slowing of EEG background activity during encephalopathy, which promptly reverted back to normal along with clinical improvement following withdrawal of valproate. To our knowledge, this is the first documentation of valproate-induced hyperammonemic encephalopathy enhanced by topiramate from India. We intend to alert internists, pediatricians, psychiatrists and neurologists about this underrecognized adverse effect of antiepileptic drug polytherapy.

Ammonia↗

PubMed2005

[Valproate-caused encephalopathy].

Valproate is a widely used antiepileptic drug with rarely occurring serious side effects. We observed two cases of valproate-caused encephalopathy of insidious type. Ten months after initiation of valproate treatment, the two patients showed neurologic deficits such as rapid cognitive decline and extrapyramidal manifestations. However, the patients recovered some weeks after termination of the treatment. This side effect must be considered in patients showing signs of rapidly progressing severe dementia who are being treated with valproate.

Aged↗

PubMed2002

Continuous veno-venous haemodiafiltration in sodium valproate overdose complicated by cerebral oedema: a case report.

A case of severe sodium valproate overdose is presented in which continuous venovenous haemodiafiltration was used. However, following the commencement of dialysis and a fall in the serum valproate levels, the patient developed cerebral oedema. This case demonstrated a poor correlation between serum valproate and its toxic effects and the lack of benefit of continuous venovenous haemodiafiltration in the management of sodium valproate overdose.

Journal Article↗

PubMedDate not supplied

Prolonged use of phenytoin, carbamazepine or valproate monotherapy on plasma levels of folate and B(12): a comparison between epileptic patients with or without cardiovascular disorders.

PURPOSE: Previous studies showed an association between the blood levels of folate and vitamin B(12) and the risk for cardiovascular disease. The aim of this study is to investigate the effect of chronic use of phenytoin, carbamazepine or valproate monotherapy on the plasma levels of folate and B(12), and to compare folate and B(12) levels in epileptic patients with or without cardiovasular disorders. METHODS: The study was conducted in the outpatient neurology clinic at Bahrain Defence Force (BDF) Hospital between January-July, 2005. Medical information was obtained by interviewing the patients and examining their hospital records. Blood folate and vitamin B(12) were measured by Immulite immunoanalysis assay using chemoluminescence. RESULTS: A total of 26 consecutive outpatients (17 males, 9 females) were recruited in the study. Their mean age +/- SD was 38.2 +/- 20.1 year (range 15-77 year). Five (19.2%) had complex partial epilepsy and the remainder had tonic-clonic seizures. They had epilepsy for 15.7 +/- 8.1 years (range 2-35 years). Thirteen of them used phenytoin, nine carbamazepine and four used valproate. The duration of the treatment (years), dose (mg/day) and serum concentration (micromol/l) were 18.3 +/- 10.6, 376.9 +/- 180.4, 41.6 +/- 25.6, for phenytoin, 14.5 +/- 11.7, 422.2 +/- 175.0, 31.1 +/- 15.9 for carbamazepine and 18.3 +/- 6.3, 400, 567.7 +/- 78.1 for valproate, respectively. Eleven (42.3%) had established cardiovascular disorders such as hypertension, myocardial infarction or stroke. The mean level of plasma folate (12.94 +/- 6.76 ng/ml) and B12 (484.94 +/- 191.25 pg/ml) in epileptic patients with cardiovascular disorders compared to their values (11.27 +/- 5.84), (514.49 +/- 225.31) respectively in epileptics with no cardiovascular disorders were not statistically significant in the two groups. CONCLUSION: In epileptic patients on chronic therapy with phenytoin, carbamazepine or valproate folate and B(12) levels were not different in patients with or without cardiovascular disorders.

Adolescent↗

PubMed1991

[Effect of sodium valproate on bicuculline-induced epileptiform activity in rat hippocampal slices in vitro].

Experiments were conducted on the rat hippocampal slices in vitro with the superfusion of bicuculline (Bcl, 10 mumol/L) and stimulation of Schaffer collaterals by single pulse to produce epileptiform activity of the pyramidal cells in CA1 area. In these experiments the effect of constant microinjection of sodium valproate onto the surface of slice on the epileptiform activity was studied. The results showed that the valproate, in concentration of 20, 30, 50 and 100 mmol/L, inhibited the Bcl-induced epileptiform activity in a manner of dose-dependence. It was deduced that the inhibition of epileptiform activity by the valproate is possibly related to the recovery of and increase in the inhibition mediated by GABAergic neurons and may be also to the non-synaptic mechanism of the valproate in rat hippocampus.

Animals↗

PubMed1990

Usefulness of valproate sodium for treatment of incontinence after ileoanal anastomosis.

We report on the excitatory effect of gamma-aminobutyric acid, which increased after the oral administration of valproate sodium, on anal canal resting pressure in human beings, gamma-aminobutyric acid receptors. We used this drug in order to improve continence after ileoanal anastomosis. Seventeen patients (eight with ulcerative colitis and nine with adenomatosis coli) were tested after receiving ileoanal anastomosis. The placebo showed no effect, but valproate sodium could ameliorate frequent defecation and soiling and the resulting perianal skin complications. Increasing anal resting pressure was also observed during valproate sodium administration without the amplitude, frequency of peristaltic wave, or voluntary squeeze pressure being affected. These results suggest that the subchronic administration of valproate sodium may be useful in the treatment of minor incontinence after ileoanal anastomosis.

Adult↗

PubMed1989

Valproate in psychiatric disorders: literature review and clinical guidelines.

A growing literature suggests that the anticonvulsant medication valproate may be effective and well tolerated in the acute and prophylactic treatment of some mood and psychotic disorders, particularly the manic phase of bipolar disorder and schizoaffective disorder. Valproate may sometimes be effective even in those patients who have not responded to conventional somatic therapies. This article reviews the pharmacokinetics, neurologic uses, and side effects of valproate, discusses the drug's efficacy in the treatment of primary psychiatric disorders, and presents clinical guidelines for the use of valproate.

Bipolar Disorder↗

PubMed1989

The use of valproate in the treatment of mentally retarded persons with typical and atypical bipolar disorders.

The author reports five cases of bipolar disorder in mentally retarded adults that were managed by treating the patients with divalproex sodium, a valproate derivative. Two patients had chronic mania (one of whom had Fragile X syndrome), two patients had rapid cycling illness (one of whom had an autistic disorder), and one patient had a classic bipolar disorder superimposed on an autistic disorder. Four of the patients had marked responses to valproate and the fifth patient had a moderate response. Valproate blood levels were within the usual therapeutic range of 50 micrograms/mL to 100 micrograms/mL. These results demonstrate the effectiveness of valproate in the treatment of mentally retarded patients with typical and atypical bipolar disorders.

Adult↗

PubMed1986

Hyperammonaemia and hepatotoxicity during chronic valproate therapy: enhancement by combination with other antiepileptic drugs.

Erythrocyte (ENH3) and plasma (PNH3) ammonia levels, liver function tests and plasma valproate concentration were measured in 81 epileptic patients, comprising three therapeutic groups: Group 1 (23 patients) received sodium valproate (VPA) monotherapy, group 2 (33 patients) received sodium valproate combined with phenytoin, carbamazepine, phenobarbitone and/or primidone and group 3 (25 patients) received one or more of these anti-epileptic drugs without sodium valproate. The mean ENH3 and PNH3 of patients in group 1 (41.1 +/- 30.7 mumol l-1 and 37.1 +/- 31.8 mumol l-1, respectively) and group 2 (44.5 +/- 21.3 and 37.6 +/- 21.4 mumol l-1, respectively) were significantly (P less than 0.01) higher than those in group 3 (28.7 +/- 10.6 and 21.5 +/- 7.8 mumol l-1, respectively) and the reference range (30.1 +/- 7.9 and 20.8 +/- 5.7 mumol l-1, respectively). Hyperammonaemia was more prevalent amongst patients in group 2, for both ENH3 (45.5%) and PNH3 (54.6%), than amongst patients in group 1 (30.4% and 52.2%, respectively) and group 3 (8% and 8%, respectively). There was a significant (P less than 0.05) positive correlation between plasma VPA and total bilirubin concentrations. Chronic VPA therapy was also associated with an increase in bilirubin concentrations measured on average four months apart.

Adolescent↗

PubMed1987

Sodium valproate: its use in primary psychiatric disorders.

Sodium valproate has been reported to be effective in the treatment of recurrent major affective and schizoaffective disorders. The records of 36 consecutive patients with various psychiatric diagnoses, who received valproate at our center, were retrospectively reviewed. None of these patients displayed a diagnosable neurologic disorder or paroxysmal EEG activity. Sixteen (44%) of the 36 patients experienced a moderate to marked response to valproate. The diagnoses of bipolar or schizoaffective disorder and the presence of nonparoxysmal EEG abnormalities both predicted a favorable response. The authors conclude that valproate deserves further study as a possible treatment for major affective disorder.

Adolescent↗

PubMed1978

Sodium valproate: dose-plasma level relationships and interdose fluctuations.

Individual dose-plasma level relationships were studied in 14 chronically treated epileptics, 10 of whom were concomitantly receiving other anticonvulsants besides valproate. Linear regression analysis showed each individual relationship to be linear with correlation co-efficients ranging from 0.9137 to 0.9997. A considerable inter-individual variation was found to exist in the slopes of the regression lines (range: 0.86 to 5.72). This may be the consequence of differences in absorption characteristics and metabolic handling of the drug. The results indicate that a proportional rise in plasma sodium valproate levels can be expected following dosage increments in an individual patient. Hourly plasma sodium valproate measurements for 6 hours between 2 successive doses, in the same group of patients, showed that the mean percentage change in post-dose peak plasma levels was 44.5%, and range from 20.7 to 153.5%. Plasma levels returned to values close to pre-dose starting levels 6 hours after the administration of a dose. The large degree of inter-dose fluctuation between doses indicates that it is preferable to use pre-dose plasma sodium valproate levels to guide the clinical management of epileptic patients.

Adolescent↗

PubMed1985

The effect of valproate on blood metabolite concentrations in spontaneously diabetic, ketoacidotic, BB/E Wistar rats.

Valproate is an effective anticonvulsant which is rarely associated with hepatotoxicity. It has profound effects on the intermediary metabolism of isolated rat hepatocytes. In this paper the effect of valproate on blood metabolite concentrations in spontaneously diabetic BB/E rats has been studied. Valproate causes a marked fall in blood ketone body concentrations and a smaller fall in blood glucose concentrations following either oral or intraperitoneal administration. Valproate may have a role in the treatment of patients with "brittle" diabetes.

Animals↗

PubMed1983

[Monotherapy with sodium valproate in generalized primary epilepsy. 2d phase: Study of long-term efficacy and tolerance].

From the analysis of 115 cases of primary generalized epilepsies treated for a mean duration of 43 months with sodium valproate as sole therapy, it appears that: the mean effective daily dosage is 21 mg/kg; the efficacy of valproate proved excellent in 82.6% of cases (seizures fully controlled: 74%, seizures occurring exceptionally: 9%); a loss of activity was never observed; in these circumstances of prolonged administration of the drug, no signs of major intolerance were seen; side-effects occurred in 29% of cases, including 20% long-term effects (weight gain, essential tremor); 64 series of laboratory tests including 15 parameters made it possible to evaluate the hematological, hepatic and pancreatic tolerance of valproate: the majority of the tests were normal. The authors believe that during long-term therapy with valproate, monitoring does not need to include the routine performance of liver function tests, but that it would be more advisable, should a suggestive clinical sign be noted, to investigate the platelet count, coagulation (partial activated thromboplastin time) and protein synthesis (fibrinogen).

Adult↗

PubMedDate not supplied

[Monozygotic twins with centrotemporal spikes on the electroencephalogram--differences in clinical manifestations and the effect of valproate therapy].

Monozygotic twin sisters who had almost identical electroencephalographic abnormalities, but different clinical features and different response of this abnormalities to valproate at the age of 6 years are described. One twin was admitted to the hospital because of numerous brief myotonic seizures of sudden onset with corresponding abnormalities in the electroencephalogram. The seizures disappeared completely and the electroencephalogram became normal within a week of treatment with valproate. The other twin never had any seizures. However, her electroencephalogram repeatedly showed impressive abnormalities and the therapy with valproate had no substantial effect on these abnormalities. We believe this twins to be a suitable model for studying the inheritance of epilepsy and electroencephalographic abnormalities, as well as for studying the action of antiepileptic drugs. At this moment, it is not possible to offer any reasonable explanation for the normalization of the electroencephalographic abnormality during valproate treatment in the clinically affected twin, while the electroencephalogram remained abnormal in the clinically unaffected twin.

Child↗

PubMed1994

Concurrent use of clozapine and valproate in affective and psychotic disorders.

BACKGROUND: This pharmaco-epidemiologic study was undertaken to determine if the combination of clozapine and valproate poses an increased risk of blood dyscrasias, liver function abnormalities, or other side effects and to develop dosing guidelines when the combination is utilized. METHOD: The charts of 55 patients receiving clozapine and valproate concurrently between May 8, 1989, and May 8, 1992, were reviewed to determine the indication for and length of time on each medication, abnormalities in liver function test results, blood cell dyscrasias, seizures, nausea, vomiting, sedation, sialorrhea, and enuresis. In addition, the efficacy of the combination was measured. RESULTS: The combination of clozapine and valproate was efficacious and well tolerated in the majority of patients. Major adverse effects such as blood dyscrasias or seizures were not experienced by the study population. The side effect that led to discontinuation of the combination most frequently was sedation. CONCLUSION: The combination of clozapine and valproate is safe and efficacious.

Adult↗

PubMed1976

[The influence on the thyroid hormone system by long-term anticonvulsive therapy with valproat (author's transl)].

Valproat lowers the serum concentraiton of PBI and T4 in epileptic children. Since this reduction is not so pronounced with PBI as with T4, the difference in comparison with the controls could not be statistically verified with the desired probability of error. The reduction of general thyroxine can be statistically verified when compared with healthy control individuals. Free thyroxine is not influenced by Valproat therapy. The TBG TSH and the T3 in vitro test do not indicate variations from the healthy control subjects. The same is true for serum cholesterol. Valproat does not cause hypothyroidism; the reduction in PBI values and T4 serum concentration must be explained by competative displacement out of the protein bonds by Valproat.

Acetates↗

PubMed1993

The manic syndrome: factors which may predict a patient's response to lithium, carbamazepine and valproate.

Studies suggest that 80% to 90% of all patients in the manic state respond to lithium provided that they are relatively free of dysphoria ("pure mania"). In contrast, less than 40% of individuals in the manic state who cycle rapidly or are substantially dysphoric ("dysphoric mania") respond to lithium. These patients appear to be more responsive to carbamazepine and valproate. The authors conclude that carbamazepine and valproate are the drugs of choice if one desires to treat a rapidly cycling individual or patient with dysphoric mania with just one agent. However, they emphasize that a prospective study designed to identify the predictors of response of primary mania to lithium, carbamazepine and valproate is required. Studies assessing the relative value of lithium, carbamazepine or valproate as prophylactic agents in the care of patients with specific subtypes of mania are also needed. These studies would address the most important issues confronting researchers interested in the drug treatment of mania.

Bipolar Disorder↗

PubMed1993

Effects of sodium valproate on various intestinal motor functions after ileal J pouch-anal anastomosis.

BACKGROUND: We investigate the effects of sodium valproate, a gamma-aminobutyric acid transaminase inhibitor, on the clinico-physiologic state after ileoanal anastomosis. METHODS: Twelve patients (five with ulcerative colitis and seven with familial adenomatous polyposis coli) were studied in a placebo-controlled trial. RESULTS: Placebo had no effect, but valproate increased the resting anal pressure by 22.4% and the maximum tolerable pouch volume by 20.7%. It also prolonged pouch emptying by 47.3%, with an associated improvement in stool frequency and incontinence. These results suggested that valproate improved both reservoir continence and sphincter continence. CONCLUSIONS: Only minimal side effects were noted, so the administration of sodium valproate appears to be a safe and useful adjunct for patients with ileoanal anastomosis in the early postoperative period.

4-Aminobutyrate Transaminase↗