Effect of sodium valproate and baclofen in tardive dyskinesia: clinical and neuroendocrine studies. Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects. Combined treatment of schizophrenic psychoses with haloperidol and valproate. A multicentre comparative trial of sodium valproate and carbamazepine in paediatric epilepsy. The Paediatric EPITEG Collaborative Group. Comparison of phenobarbitone, phenytoin with sodium valproate: randomized, double-blind study. Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial. A double-blind, placebo-controlled study of valproate for aggression in youth with pervasive developmental disorders. A pilot open randomized trial of valproate and phenobarbital in the treatment of acute alcohol withdrawal. [Efficacy of sodium valproate in partial epilepsy. Crossed study of valproate and carbamazepine].
Concurrent neuroleptic administration is a necessary factor in the therapeutic response to GABAergic agents. In contrast to their effect on the striatum, neither BAC nor NaV influences hypothalamic-pituitary DA function mediating PRL secretion. To determine the efficacy, tolerability, and impact on quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoin or sodium valproate in patients after craniotomy.
                A prospective, stratified, randomised, double blind single centre clinical trial was performed, comparing two groups of 50 patients each, who underwent craniotomy for different pathological conditions and who were treated for 1 year after surgery with either 300 mg phenytoin/day or 1500 mg sodium valproate/day. During the study period patients were seen in the outpatient clinic at 1.5, 3, 6, and 12 months, when medical history, adverse events, and drug plasma concentrations were evaluated. Neuropsychological functioning and quality of life were assessed on the last three visits. In cases of a seizure an EEG was performed, drug plasma concentration assessed, and medication subsequently increased.
                Of the 100 included patients 14 (seven in each group) experienced one or more postoperative seizures. Severity of the seizures was comparable in the two groups. In all patients, drug plasma concentrations were in the low or subtherapeutic ranges at the time of the first postoperative seizure. Five patients in the phenytoin group and two in the valproate group had to stop their treatment due to drug related adverse events. Sixty patients completed the 12 month period. Analysis of neuropsychological and quality of life data showed no significant differences.
                For efficacy, tolerability, impact on cognitive functioning, and quality of life, no major differences were found between phenytoin and valproate prophylaxis. Valproate is an alternative for anticonvulsant prophylaxis in patients after craniotomy. In accordance with a previous study of adjuvant effects of the anticonvulsant carbamazepine (CBZ) on the neuroleptic treatment of schizophrenic psychoses, the effects of valproate (VPA) were tested in a randomly assigned double-blind, placebo-controlled study. Apart from a (statistically nonsignificant) psychopathological deterioration following discontinuation of VPA while on continuous neuroleptic mediation after four weeks and a statistically significant effect on "hostile belligerence", no overall therapeutic effects of the combination of haloperidol (HPD) with VPA were observed under controlled conditions. Unlike the results with CBZ, concomitant use of VPA led to an even higher consumption of haloperidol and biperiden and to a higher rate of extrapyramidal symptoms compared with the corresponding placebo group, although these differences did not attain statistical significance. In regard to use of the sedative neuroleptic chlorprothixene, there was a trend toward lower doses in the VPA group than in the placebo group. From these results, adjuvant effects like those of carbamazepine in the neuroleptic treatment of schizophrenic psychoses could not be confirmed for valproate in the present study. However, the trend toward lower doses of sedative medication and observed effects on "hostile belligerence" may indicate sedative and/or antimanic properties of valproate which have recently been demonstrated in several controlled studies. The long-term efficacy and adverse-event profiles of sodium valproate and carbamazepine in children with newly diagnosed primary generalised or partial epilepsy were compared at 63 outpatient clinics. Children with two or more generalised tonic-clonic or partial seizures in the previous six months were randomised to oral sodium valproate (N = 130) or oral carbamazepine (N = 130) and followed for three years as outpatients. Dosages were increased as needed until seizures were controlled or toxicity developed. Sodium valproate and carbamazepine were equally effective in achieving high levels of seizure control in both primary generalised seizures and partial seizures with or without generalisation. Adverse events were mostly mild, few necessitating drug withdrawal. Those particularly associated with valproate were weight increase, alopecia and appetite increase, and with carbamazepine, rashes, somnolence, diplopia and abnormal gait/ataxia. To compare the efficacy and side effects of phenobarbitone (PB), phenytoin (PHT) and sodium valproate (SVP) in controlling generalized tonic-clonic convulsions (GTC).
                Randomized, double blind clinical trial.
                Out-Patients in a tertiary care hospital.
                151 children with GTC, aged 4-12 yrs, from Madras city were enrolled. At the end of 2 yrs, 127 children remained in the study.
                Each child was given one active drug and 2 placebo tablets. Clinical, hematological and biochemical evaluations were done every month. Serum drug levels were assessed periodically.
                Recurrence of convulsion and side effects.
                The proportion of children with recurrence did not differ among the 3 groups. More than one side effect was observed in 16 (32%) children on PB, 20 (40%) children on PHT and 9 (19%) children on SVP and this difference was statistically significant (p < 0.05). Hyperactivity was the major side effect of PB, observed in 22% of children.
                All 3 drugs were equally effective in controlling seizures. Side effects were minimal with SVP followed by PB. Though side effects were more frequent with PHT, most of them disappeared on adjusting drug dosage. Least expensive phenobarbitone may be preferred as the first drug of choice but, only for pre-school children. SVP is advised for school going children. Recent studies have shown that most newly diagnosed epileptic patients can be satisfactorily treated with a single antiepileptic drug. We therefore undertook a prospective randomised pragmatic trial of the comparative efficacy and toxicity of four major antiepileptic drugs, utilised as monotherapy in newly diagnosed epileptic patients. Between 1981 and 1987 243 adult patients aged 16 years or over, newly referred to two district general hospitals with a minimum of two previously untreated tonic-clonic or partial with or without secondary generalised seizures were randomly allocated to treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform with standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to enter one year remission. The overall outcome with all of the four drugs was good with 27% remaining seizure free and 75% entering one year of remission by three years of follow up. No significant differences between the four drugs were found for either measure of efficacy at one, two, or three years of follow up. The overall incidence of unacceptable side effects, necessitating withdrawal of the randomised drug, was 10%. For the individual drugs phenobarbitone (22%) was more likely to be withdrawn than phenytoin (3%), carbamazepine (11%), and sodium valproate (5%). In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures, the choice of drug will be more influenced by considerations of toxicity and costs. The aim of this study was to study valproate efficacy and safety for aggression in children and adolescents with pervasive developmental disorders (PDD).
                In this prospective double-blind, placebo-controlled study, 30 subjects (20 boys, 10 girls) 6-20 years of age with PDD and significant aggression were randomized and received treatment with valproate (VPA) or placebo (PBO) for 8 weeks as outpatients. Mean VPA trough blood levels were 75.5 mcg/mL at week 4 and 77.8 mcg/mL at week 8.
                No treatment difference was observed statistically between VPA and PBO groups. The Aberrant Behavior Checklist--Community Scale (ABC-C) Irritability subscale was the primary outcome measure (p = 0.65), and CGI--Improvement (p = 0.16) and OAS (p = 0.96) were secondary outcome measures. Increased appetite and skin rash were significant side effects. Only 1 subject was dropped from the study owing to side effects, notably a spreading skin rash, which then resolved spontaneously. Two subjects receiving VPA developed increased serum ammonia levels, one with an associated parent report of slurred speech and mild cognitive slowing. Poststudy, of 16 VPA and PBO subjects receiving VPA, 10 subjects demonstrated sustained response, 4 of whom later attempted taper, with significant relapse of aggression.
                The present negative findings cannot be viewed as conclusive, partly owing to the large placebo response, subject heterogeneity, and size of the groups. Larger studies are needed to expand upon these findings. The authors conducted a randomized, open comparison of the GABAergic anticonvulsant sodium valproate (divalproex sodium; Depakote) and phenobarbital as an active control in the management of acute withdrawal from alcohol. Repeated measures ANOVA was used to assess treatment effects in the first 37 inpatients, evaluating mood, hostility, and subjective and objective measures of withdrawal at index, 3, and 5 days of detoxification. Subjective and objective ratings of abstinence symptoms and subjective mood disturbance decreased significantly in intensity in both groups over 5 days, but there were no significant treatment differences nor treatment by time interactions. Hostility scores did not differ overall, but a group by time effect was observed (F = 5.42, df = [1,13], P < 0.05), with phenobarbital subjects reporting less hostility/aggression than those in the valproate group. There were no withdrawal-related seizures or other acute sequelae. This study offers pilot confirmation that sodium valproate is as effective as phenobarbital in the management of acute alcohol withdrawal, but it is unclear whether valproate offers a clinical advantage with respect to stabilizing changes in mood and interpersonal hostility during detoxification. An open response-conditional cross-over study of valproate versus carbamazepine has been done in previously untreated patients with partial seizures. Thirty-one patients entered the study. Nineteen were followed up to one year. It appeared that valproate was at least as effective as carbamazepine: at one year, 11 patients were seizure-free on valproate and only 8 were seizure-free on carbamazepine. Furthermore no side-effect was noted in valproate therapy, whereas carbamazepine was stopped in 2 patients because of skin rashes. The efficacy of sodium valproate in partial epilepsy remains controversial. It is of course limited when given as co-therapy in severe epilepsies, uncontrolled with other major antiepileptic drugs. However in naive patients, with recent and previously untreated partial epilepsies, a one-drug treatment with valproate appears to be as effective as carbamazepine or phenytoin. It has less unwanted side-effects and should be prescribed as first line treatment.
Evidence of the effects of baclofen, progabide, sodium valproate, or THIP for people with antipsychotic-induced TD is inconclusive and unconvincing. Any possible benefits are likely to be outweighed by the adverse effects associated with their use.