Which drug for the adult epileptic patient: phenytoin or valproate? Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects. Comparison of phenobarbitone, phenytoin with sodium valproate: randomized, double-blind study. Comparison of sodium valproate and phenytoin as single drug treatment in generalised and partial epilepsy. Impact of valproate and phenytoin on cognitive function in elderly patients: results of a single-blind randomized comparative study. Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial. Comparison of sodium valproate and phenytoin as single drug treatment in epilepsy. Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy. A prospective study between carbamazepine, phenytoin and sodium valproate as monotherapy in previously untreated and recently diagnosed patients with epilepsy.
A series of 140 previously untreated patients with tonic-clonic or partial seizures were randomised to receive either phenytoin or sodium valproate. There was no difference between the treatment groups in pretreatment variables that might influence outcome. Sodium valproate and phenytoin in the treatment of tonic-clonic or partial seizures showed no difference in efficacy as regards time to two year remission or time to first seizure. When the possible prognostic factors were studied, including history and results of clinical examination and investigations before treatment; the only factor which influenced the proportion of patients achieving two year remission was type of seizure. Patients with a clinical history of partial seizures did significantly less well than those with a history of tonic-clonic seizures only. This study showed no major difference in efficacy between sodium valproate and phenytoin in adults with recent onset of epilepsy, irrespective of the type of seizures that the patient suffered. 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. 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. Ninety four patients of generalised and partial epilepsy were randomly assigned to treatment with sodium valproate (49 cases) or phenytoin (45 cases). Serum levels were monitored. Cases were evaluated after 4, 12, 24 weeks of treatment. Both drugs were found to be equally effective in controlling generalised seizures. However, valproate is better in partial seizures. No correlation could be established. Side effects were minor with both the drugs. Thirty-eight patients (median age 77 years; range 62-88 years) with elderly-onset seizures were entered into a single-blind, randomized study designed to compare the impact of phenytoin (PHT) and valproate (VPA) on cognitive function. A stratified minimization program matched the two groups for age, sex, and seizure type. Attention, concentration, psychomotor speed, and memory were assessed twice before treatment (to minimize practice effects), at 6 weeks and (for patients remaining in the study) at 3 months, 6 months, and 1 year by an extensive battery of psychologic tests. Changes in cognitive function were minor, and some tended toward improvement. Contrary to expectation, there was little difference between PHT and VPA with regard to impact on cognitive function. Frequent noncognitive adverse effects were reported. Thus, we did not replicate the findings of previous literature. We conclude that antiepileptic drug (AED) monotherapy as used in our trial did not produce significant adverse cognitive effects. The choice of AED in the elderly may therefore be more influenced by consideration of other adverse effects. 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. Thirty-three epileptic patients were randomly divided into two treatment groups. One group of 18 patients was given sodium valproate; the other 15 patients were given phenytoin. Periods of treatment ranged from 9 t0 48 months (mean, 30 months). Any patient who developed a seizure while on the first drug was changed to the other drug, provided the serum level of the first drug was in the accepted therapeutic range. Six required the change from phenytoin to sodium valproate, and three from sodium valproate to phenytoin. Side effects were not a major problem with either drug during the trial period. Phenytoin has been widely prescribed alone; our results indicate that sodium valproate may also be used as a single drug in the treatment of several types of epilepsy. The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients. We know of only one randomised comparative trial (of two drugs) in newly diagnosed childhood epilepsy. We have undertaken a long-term, prospective, randomised, unmasked, pragmatic trial of the comparative efficacy and toxicity of four standard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy.
                Between 1981 and 1987, 167 children aged 3-16 years, who had had at least two previously untreated tonic-clonic or partial seizures, with or without secondary generalisation, were randomly allocated treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform to standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission.
                The overall outcome with all four drugs was good. 20% of children remained free of seizures and 73% had achieved 1-year remission by 3 years of follow-up. We found no significant differences between the drugs for either measure of efficacy at 1, 2, or 3 years of follow-up. The overall frequency of unacceptable side-effects necessitating withdrawal of the randomised drug was 9%. This total included six of the first ten children assigned phenobarbitone; no further children were allocated this drug. Of the other three drugs, phenytoin (9%) was more likely to be withdrawn than carbamazepine (4%) or sodium valproate (4%). INTERPRETATION Our data will inform choice of drug and outcome with four of the standard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children. One hundred and eighty one patients with previously untreated epilepsy were randomised to sodium valproate, phenytoin or carbamazepine as monotherapy and followed up for a median period which ranged from 14 to 24 months. All three drugs were highly effective in the control of generalised seizures but less effective for partial seizures. Excellent or good control was achieved with therapeutic levels of sodium valproate and carbamazepine, but with subtherapeutic levels of phenytoin.
We have not found evidence that a significant difference exists between phenytoin and valproate for the outcomes examined in this review. Results do not apply to absence or myoclonus. No outright evidence was found to support or overthrow current treatment policies.