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PubMed1979

Sodium valproate in the prophylaxis of simple febrile convulsions.

Thirty children with simple febrile convulsions were treated with sodium valproate following their second convulsion. Twenty-two of the 30 (73%) had no further convulsions during the one-year period of observation compared with 17 of 28 in the control group (61%). This was not a statistically significant difference. Side effects attributed to sodium valproate treatment were noted in 7 patients (23%), although 4 of these showed only mild transient gastrointestinal symptoms at high dosage. The study did not confirm any advantage in the use of sodium valproate as a prophylaxis for febrile convulsions, although compliance was good and significant side effects infrequent.

Chemical and Drug Induced Liver Injury↗
PubMed1976

Effect of sodium valproate on tardive dyskinesia.

The effect of sodium valproate, a drug which has been demonstrated to increase gamma-aminobutyric acid levels in the CNS, on tardive dyskinesia and psychiatric symptoms was investigated in a double-blind cross-over study on 32 chronic psychiatric patients. The oro-facial dyskinesias were totally or significantly relieved in 17 cases. During the active treatment period the involuntary movements of the extremities and dystonic spasms were also significantly relieved in 7 out of 9 patients. In two patients, however, the extrapyramidal symptoms became slightly worse. A significant improvement was noted in the psychiatric symptoms of 14 out of 32 patients during sodium valproate administration. The psychiatric state of 4 out of 32 patients deteriorated. Three was no correlation between the serum concentration of sodium valproate and its effect on the dyskinesia or on the psychiatric symptoms. Some of the elderly subjects showed a slight accumulation of the drug.

Age Factors↗
PubMed1978

Rectal administration of sodium valproate in status epilepticus.

Six patients suffering from status epilepticus were refractory to parenteral treatment with either diazepam, amobarbital or both, and were given sodium valproate 200 to 800 mg every 6 hours. The drug was administered rectally as 200 mg lipid-based suppositories, thereby avoiding impaired absorption, which occurs in the presence of paralytic ileus. Plasma levels of sodium valproate in all patients reached the therapeutic range within 36 hours of starting therapy. Seizures were totally controlled in five patients and a 75 percent reduction was noted in the sixth. In two patients, the route of administration was changed from rectal to an equivalent oral dose with continuing control of seizures and minimal change in plasma levels, suggesting that bioavailability is similar for the two forms of the drug. The rectal route of administration was effective in achieving systemic absorption of sodium valproate in the treatment of status epilepticus.

Adolescent↗
PubMed1979

Sodium valproate: serial monitoring of EEG and serum levels.

The clinical and electroencephalographic (EEG) effects of sodium valproate were studied in four patients by means of serial 24-hour EEG recordings and simultaneous hourly determinations of serum drug concentrations. The patients all had frequent clinical seizures and generalized spike-wave discharges. Valproate appeared to reduce diurnal paroxysmal discharges (PD) and clinical seizures, but the effect on nocturnal PD was less marked. The extent and duration of the depression of PD and seizures varied. Altering the distribution of the total daily dose may change the pattern of clinical seizures and PD. Valproate concentrations fluctuated widely over 24 hours, and the significance of single estimations often cited in the literature appears dubious. Peak serum concentrations above 100 micrograms per milliliter may be necessary in some patients to achieve clinical and EEG improvement.

Adolescent↗
PubMed1977

The anticonvulsant action of sodium valproate (Epilim) in 100 patients with various forms of epilepsy.

Sodium valproate (Epilim) has been used in the management of 100 patients with previously uncontrolled epilepsy for periods up to 2 years. If all manifestations of epilepsy are considered together, 75% to 100% control of seizures was achieved in 43% of patients, 25% to 74% control in 26%, and no improvement occurred in 31% of patients. Control of 75% to 100% was achieved in 57% of patients with a spike and wave electroencephalogram (EEG) disturbance but only in 35% of those with focal abnormalities, excessive slow activity, or normal records. When the various manifestations of epilepsy were considered individually, the greatest improvement was found among the patients with the minor forms of generalized epilepsy (petit mal absences, myoclonus and atonic attacks) in whom 75% to 100% control was obtained in 67%, compared with 43% of those with major generalized seizures (grand mal) and 30% of those with temporal lobe attacks and other forms of focal epilepsy. Gastrointestinal disturbances and drowsiness were noted as side effects in the early stages of treatment, but the majority of patients tolerated the drug well and many commented on increased mental alertness while taking it. Two patients were over-stimulated and some noticed tremor or twitching as side effects. Some minor abnormalities in blood coagulation studies were noted, but these were transient and did not appear to be of clinical significance. Regular blood counts and biochemical studies have not shown any significant changes. Sodium valproate appears to be a safe and useful anticonvulsant with the advantage that it usually makes patients brighter rather than drowsier. Abnormalities of platelet function have been described in some overseas reports, so that any unexplained bruising or bleeding in a patient taking valproate is an indication for a platelet count and coagulation studies.

Adolescent↗
PubMed1978

[Double-blind study on the anti-convulsive effect of phenobarbital and valproate in the Lennox syndrome].

In a double-blind crossover trial valproate was compared with phenobarbital with regard to anticonvulsive activity and tolerance in 17 epileptic children (mean age 55 +/- 26 months) with Lennox syndrome. Valproate in association with a phenobarbital dose reduced by about 40% proved to be to a statistically significant degree more active against epileptic seizures than phenobarbital alone. No difference in the effect on the EEG tracings was observed. Valproate appeared to be somewhat more active than phenobarbital with regard to behaviour, but the difference was not significant. Tolerance to both products was equally good.

Benzodiazepines↗
PubMed1977

Plasma sodium valproate levels and clinical response in epilepsy.

Serial plasma levels of sodium valproate were estimated in 12 epileptic patients and 10 normal subjects after a single dose of the drug, whilst random estimations were performed in another group of 32 patients already stabilised on sodium valproate. The tentative conclusions arrived at by this study were: 1) In the majority of patients and normal subjects peak plasma levels were reached by the end of the first or second hour. 2) The majority of clinically controlled subjects showed a plasma level above 40microgram/ml. 3) Similar doses of sodium valproate (mg/kg) produced higher plasma levels in normal subjects than in the epileptic patients. Whether this is an effect of other anticonvulsants the patients were taking at the same time is a matter for conjecture. 4) Dosage and plasma levels did not appear to show a close correlation. 5) Random estimation of plasma levels are of little value for monitoring therapeutic efficacy, unless timed in relation to the dose, for reasons already mentioned above.

Anticonvulsants↗
PubMed1975

Sodium valproate in the management of intractable epilepsy: comparison with clonazepam.

Sodium valproate 400 mg.-1800 mg. daily has been used for 1-4 months in the management of 35 patients with intractable epilepsy. This preliminary report indicates that the agent is a useful addition to anti-convulsant therapy with beneficial effect to the majority of patients with gran mal, petit mal, nyoclonus and akinetic attacks. Temporal lobe epilepsy and other focal cortical seizures responded less well. There were some minor gastrointestinal and neurological side-effects which subsided with time or the reduction of dosage. The transition period while other anticonvulsants were being withdrawn was accompanied by grand mal seizures in 6 patients. It appears that sodium valproate requires 7-10 days to becoms fully active and that other anticonvulsants should be withdrawn only after the patient is established on a maintenance dosage. Comparison with clonazepam suggests that the latter is more effective in the control of petit mal and temporal lobe epilepsy but has more persistent sedative effects. Most patients transferred from other anticonvulsants to sodium valproate felt more alert and able to concentrate better.

Adolescent↗
PubMed1979

Valproate sodium in refractory seizures: a study of efficacy.

Sodium valproate (N-dipropylacetic acid) is a newly released anticonvulsant drug with a broad spectrum of activity. Twenty-seven children with uncontrolled seizures, predominantly akinetic and myoclonic, were treated with this drug. Encouraging results were noted in those with head-nodding spells, body drops, and myoclonic jerks ("minor motor" seizures). Side effects included occasional gastrointestinal disturbance. No important hepatotoxic complications were noted. Two persons displayed transient neurologic side effects. Of particular interest was the noticeable improvements in mental status noted in 17 of the 27 patients. Some variations in blood level of other anticonvulsant drugs were noted, emphasizing the importance of monitoring these drugs. Valproate sodium provides important improvement in our ability to manage minor motor seizures.

Adolescent↗
PubMed1978

Urinary excretion of indican in progressive myoclonus epilepsy without Lafora bodies. The effect of sodium valproate.

Increased urinary excretion of indican was detected in earlier studies of patients with the form of progressive myoclonus epilepsy (PME) where no Lafora bodies are present in the brain and other tissues. Since then, all PME patients have been given sodium valproate and/or clonazepam. In a series of 10 patients now examined the mean excretion was on the same level as that of other epileptic and non-epileptic neurological patients (53 +/- 27 mg/g creatinine). Alternate reduction of the two drugs in one patient over a period of 24 days increased the excretion up to the high level measured earlier (96 mg/g creatinine) and caused marked worsening of the clinical condition while no remarkable changes were observed in another PME patient who received her normal medication. The highest values ever measured were found in one PME patient just before his death. In two patients who had no medication the excretion was also high but returned to the normal level during medication with sodium valproate. It is unknown at the moment whether this change is due to the improved clinical condition of the patients or to the compound itself.

Adult↗
PubMed1976

The use of sodium valproate in a case of status epilepticus.

A child in status epilepticus, who did not respond to intravenous diazepam, was treated with sodium valproate by naso-gastric tube. Subsequent clinical and encephalographic improvement appeared to be related to the sodium valproate, and its value in cases of status epilepticus is discussed.

Child↗
PubMed1976

Has sodium valproate hypnotic effects?

Eight fasting normal subjects were given a single dose of sodium valproate, 400 mg, phenobarbital, 60 mg, or the two drugs in combination, in a double-blind placebo-controlled study. The effects were assessed behaviorally and by a standard 30-min EEG, begun 1 hr after the treatments had been given. The recording was rated for the amount of drowsiness and sleep, independent of which drug had been given. The scores obtained indicated that valproate intself has hypnotic action, and there is a tendency for this to be increased by the simultaneous administration of phenobarbital.

Adult↗
PubMed1978

A controlled study of the effect of sodium valproate on photosensitive epilepsy and its prognosis.

The effect of sodium valproate on photosensitive epilepsy was studied. The range of flash rates of intermittent photic stimulation to which patients were sensitive (photosensitive range) was tested prior to treatment, and the reliability of this measure established by repeated tests on 70 patients. The photosensitive range was measured on 50 patients prior to and during treatment with sodium valproate. In 27 patients photosensitivity was abolished and in a further 12 patients photosensitivity was significantly reduced. A group of 167 patients followed without treatment did not show significant improvement over a 7 year period. Sixteen patients had drug treatment withdrawn, and in 7 months their photosensitive range had returned to its predrug level.

Adolescent↗
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↗
PubMed1978

Sodium valproate in Huntington's disease.

The authors assessed the effect of sodium valproate, which is thought to elevate brain gamma-aminobutyric acid (GABA) levels, in the treatment of Huntington's disease by an objective ultrasound method in three patients with Huntington's disease. Despite plasma levels ranging from 47.0 to 140.8 microgram/ml (mean, 104.7), sodium valproate had no beneficial effect on involuntary movements. The authors stress the importance of activation to achieve a standard level of arousal in the assessment of involuntary movements.

Adult↗
PubMed1979

The effect of methysergide, pimozide, and sodium valproate on the diazepam-stimulated growth hormone secretion in man.

Diazepam-induced GH secretion was tested on 28 male volunteers before and after a 3-day treatment with methysergide, pimozide, or sodium valproate. Serum GH, diazepam, and blood glucose levels were determined. Without prior medication, the mean serum GH level increased 336% 1 h after diazepam administration. Treatment with the serotonin antagonist, methysergide, had no effect on the diazepam-stimulated GH secretion, whereas pimozide, the selective dopamine receptor-blocking agent, reduced the GH response to diazepam by 50% (P less than 0.05). Sodium valproate, a gamma-aminobutyric acid transaminase inhibitor, also inhibited diazepam-induced GH secretion; stimulated GH levels were 51% at 30 min (P less than 0.025), 39% at 60 min (P less than 0.025), and 46% at 90 min (P less than 0.025) relative to the stimulated levels without medication. No difference was found in blood glucose or serum diazepam levels after the drug treatments relative to the values obtained under basal conditions. It is suggested that diazepam-induced GH secretion is at least partly mediated via dopaminergic mechanisms. Serotonin does not seem to be involved. It is further proposed that gamma-aminobutyric acid plays an inhibitory role in GH secretion.

Adult↗
PubMed1979

Tremor due to sodium valproate.

Four patients developed postural tremor after ingestion of sodium valproate. The tremor was recorded by a variable-capacitance transducer and was of the "benign essential" type. The dosages of sodium valproate varied between 1000 mg and 2000 mg daily and serum levels were between 34.9 microgram per milliliter and 154.3 microgram per milliliter. Tremor was ameliorated in two cases when the dosage was reduced. In only one case was the serum level in the toxic range for our laboratory. The pharmacology of essential tremor is unknown; production of a similar tremor by a drug could serve as a biochemical model.

Adult↗
PubMed1978

Sodium valproate (Epilim) in the treatment of refractory epilepsy.

Sodium valproate was given to seven children with refractory epilepsy and mental retardation. Four of the children became fit free while another was much improved. Plasma levels of sodium valproate correlated well with the dose prescribed and did not approach the theoretical top-desirable level of 200 microgram/ml despite larger than recommended doses. Side effects were minimal and it is concluded that the drug is safe and useful.

Adolescent↗