Placebo-controlled study of phenobarbitone and phenytoin in the prophylaxis of febrile convulsions. Behavioural effects of phenobarbitone and phenytoin in small children. Effective short-term diazepam prophylaxis in febrile convulsions. Recurrence risk after first febrile seizure and effect of short term diazepam prophylaxis. Effectiveness of intermittent diazepam prophylaxis in febrile seizures: long-term prospective controlled study. Sodium valproate in the prophylaxis of simple febrile convulsions. The first febrile seizure--antipyretic instruction plus either phenobarbital or placebo to prevent recurrence. [Preventing the recurrence of febrile seizures: intermittent prevention with rectal diazepam compared with continuous treatment with sodium valproate]. Long term outcome of prophylaxis for febrile convulsions. Intention to treat febrile convulsions with rectal diazepam, valproate or phenobarbitone. Failure of phenobarbitone to prevent febrile convulsions. Antipyretic agents for preventing recurrences of febrile seizures: randomized controlled trial. A controlled trial of diazepam administered during febrile illnesses to prevent recurrence of febrile seizures. Long-term effect of phenobarbital on cognitive function in children with febrile convulsions. The value of phenobarbital in the child who has had a single febrile seizure: a controlled prospective study. Effect of acetaminophen and of low intermittent doses of diazepam on prevention of recurrences of febrile seizures. Phenobarbital for febrile seizures--effects on intelligence and on seizure recurrence. Role of phenobarbitone in preventing recurrence of febrile convulsions. Continuous sodium valproate or phenobarbitone in the prevention of 'simple' febrile convulsions. Comparison by a double-blind trial. Long term prophylaxis of febrile seizures. Studies on prophylactic treatment of febrile convulsions in children. Is it feasible to inhibit attacks by giving drugs at the first sign of fever or infection? Diazepam versus clobazam for intermittent prophylaxis of febrile seizures. A controlled trial of pyridoxine supplementation in children with febrile convulsions. Frequent febrile episodes and recurrent febrile convulsions. [Efficacy of sodium dipropylacetate compared with phenobarbital and placebo in the prevention of recurrence of febrile convulsions]. Side effects of phenobarbital in toddlers; behavioral and cognitive aspects. Prevention of recurrent febrile convulsions--a randomized therapeutic assay: sodium valproate, phenobarbital and placebo. Intermittent prophylaxis in febrile convulsions: diazepam or valproic acid? Intermittent oral diazepam prophylaxis in febrile convulsions: its effectiveness for febrile seizure recurrence. Does phenobarbital used for febrile seizures cause sleep disturbances? Randomized, controlled trial of ibuprofen syrup administered during febrile illnesses to prevent febrile seizure recurrences. Double-blind, randomized trial of diazepam versus placebo for prevention of recurrence of febrile seizures. Behavior disturbance, phenobarbital, and febrile seizures. Late cognitive effects of early treatment with phenobarbital.
Of 138 children who had a first febrile convulsion before their second birthday, 48 were treated with phenobarbitone, 47 with phenytoin, and 43 with a placebo for 12 months. Drug levels were monitored and adverse effects of the drugs were noted. Compared with placebo, phenobarbitone significantly reduced recurrences among children under 14 months old at the time of their first convulsion, but nor among older children. Phenytoin was an ineffective prophylactic agent. Ideal drug levels were difficult to maintain, and many recurrences occurred when concentrations were suboptimal. Behavioural disturbance in children taking phenobarbitone was not a serious problem. The decision to give continuous prophylaxis for febrile convulsions is complex, and each case must be judged on its merits. For children who have a first seizure before 14 months of age prophylaxis may be advisable and phenobarbitone is effective. Mothers of 56 children under 2 years old taking phenobarbitone and mothers of 55 children taking phenytoin recorded on questionnaires changes they had noted in the children's behaviour 3 and 9 weeks after starting the drug. Severe behavioural disturbance was noted by many, but the pattern and incidence was similar to that recorded by the mothers of 50 children starting a placebo, and we attribute it to the effect of a recent hospital admission. There was a small improvement in the behaviour of 20% of children who had been taking phenobarbitone for a year when they stopped it, but in this age group the disturbance caused by phenobarbitone did not appear to have been great. The efficacy of short-term diazepam prophylaxis in febrile convulsions was evaluated in a prospective, controlled study. A total of 289 consecutive children admitted with their first febrile seizure were randomized into two groups. One group received short-term prophylaxis for 18 months with rectally administered diazepam in solution whenever the temperature was greater than or equal to 38.5 degrees C. The control group received no prophylaxis, but diazepam rectally in the event of new seizures. The short-term prophylaxis, a mean of five doses of diazepam per child per year, afforded effective seizure control; the 18-month recurrence rate was reduced from 39% to 12% (P less than 0.001), the total number of recurrences from 77 to 23 (P less than 0.001), the long-lasting recurrences from 5.0% to 0.7% (P less than 0.05). The risk of subsequent epilepsy within the first 2 years was the same, regardless of receiving prophylaxis (3%) or not (3%); it was low after simple febrile convulsions (no cases of epilepsy in 230 children) but considerable after complex febrile seizures (20%) or seizures associated with severe interictal EEG abnormalities (50%). In a prospective randomised study, 289 children admitted consecutively to hospital with their first febrile seizure were allocated, by date of admission, to short term diazepam prophylaxis (n = 152) or to no prophylaxis (n = 137) and followed for 18 months. In untreated children, five major risk factors for recurrent febrile convulsions were identified: age 15 months or less at the time of the first febrile seizure, epilepsy in first degree relatives, febrile convulsions in first degree relatives, a first complex febrile seizure, and day nursery care. The 18 month recurrence rate was 80 to 100% if three to five risk factors were present, 50% if two factors were identified, 25% where one factor was found, and 12% if there were no predictors. During prophylaxis the recurrence rate was uniformly low (mean 12%) in all risk groups. In high (three or more factors) and intermediate (two factors) risk children prophylaxis provided effective seizure control and reduced the recurrence rate from 80%, or more, to 12% and 50% to 12%, respectively. In children with one risk factor 50% of all recurrences were prevented (25% to 12%). Prophylaxis was ineffective in very low risk children (12% to 12%). The efficacy of intermittent rectal diazepam prophylaxis is assessed in the prevention of febrile seizures. In a prospective randomized cohort trial, 139 children (77 girls, 62 boys) who experienced a first febrile seizure were allocated to two groups: group A, which received intermittent diazepam (n = 68), and group B, which received no prophylaxis (n = 71). All children had a 3-year follow-up. The inclusion criteria were no personal history of afebrile seizures, normal neurodevelopment, no previous anticonvulsant therapy, and age between 6 months and 3 years. Each group was stratified to low, intermediate, and high risk according to the available clinical data. The 36-month recurrence rates in the no-prophylaxis group were 83% in high-risk patients, 55% in intermediate-risk patients, and 46% in low-risk patients. In the prophylaxis group, the recurrence rates were reduced in all risk groups: 38%, 35%, and 33%, respectively. Intermittent diazepam prophylaxis reduces the recurrence rate mainly in high-risk children provided that sufficient doses are given on time and adequately. 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. A randomized double-blind study was carried out comparing single daily dose phenobarbital plus antipyretic instruction to a placebo plus antipyretic instruction to prevent a recurrent seizure following an initial simple febrile seizure. Parents of 138 consecutive children presenting to an emergency room with a first simple febrile convulsion received verbal and written instructions about fever control. Seventy-nine then agreed to participate in this study. Children were randomized to receive either placebo with riboflavin tracer (n = 40) or phenobarbital 5 mg/kg in a single daily dose with a riboflavin tracer (n = 39) for 12 months or until another seizure occurred. Urine fluorescence for riboflavin was used to monitor compliance in all patients. Serum phenobarbital levels were obtained at each follow-up visit and averaged 1.4 mg/dl throughout the study. The significant difference (P less than 0.02) in the incidence of recurrent seizures between patients receiving phenobarbital (2/39) and those receiving placebo (10/40) suggests that a single daily dose of phenobarbital is more effective than counseling parents about antipyretic therapy in preventing recurrent seizures following an initial febrile seizure. Sixty nine children suffering from a first febrile seizure without evidence of neurologic disorder or associated risk factors were randomly assigned to one of three groups: no treatment; intermittent rectal diazepam; or continuous oral sodium valproate. All patients were followed for two years. Periodical controls were performed every three months in order to record febrile episodes, recurrent seizures, and treatment side affects. Rate of recurrent febrile seizures was 16% in control group, and 5.5% in diazepam group. Sodium valproate group showed no recurrences in the follow-up period. The low relapsing rate in control group suggests that prophylaxis should not be established even if it is requested by certain parental attitudes. A cohort of 289 children with febrile convulsions who had been randomised in early childhood to either intermittent prophylaxis (diazepam at fever) or no prophylaxis (diazepam at seizures) was followed up 12 years later. The study focused on the occurrence of epilepsy and on neurological, motor, intellectual, cognitive, and scholastic achievements in the cohort. At follow up the two groups were of almost identical age (14.0 v 14.1 years), body weight (58.2 v 57.2 kg), height (168.2 v 167.7 cm), and head circumference (55.9 v 56.2 cm). The occurrence of epilepsy (0.7% v 0.8%), neurological examination, fine and gross motor development on the Stott motor test, intellectual performance on the Wechsler intelligence scale for children verbal IQ (105 v 105), performance IQ (114 v 111), and full scale IQ (110 v 108), cognitive abilities on a neuropsychological test battery, including short and long term, auditory and visual memory, visuomotor tempo, computer reaction time, reading test, and scholastic achievement were also very similar. Children with simple and complex febrile convulsions had the same benign outcome. The long term prognosis in terms of subsequent epilepsy, neurological, motor, intellectual, cognitive, and scholastic ability was not influenced by the type of treatment applied in early childhood. Preventing new febrile convulsions appears no better in the long run than abbreviating them. One hundred and eighty-six consecutive children aged between six and 72 months admitted to the Manchester Children's Hospitals with a febrile convulsion in the first year of life, a complicated febrile convulsion, or more than one febrile convulsion within two years, were allocated randomly to one of three groups who were offered rectal diazepam in the event of a subsequent prolonged febrile convulsion, or prophylactic treatment with sodium valproate or phenobarbitone. Over-all risk of recurrence was 30 per cent and adequate prophylactic treatment did not lessen this risk. Side-effects in 24 per cent of the valproate group and 61 per cent of the phenobarbitone group did not justify the use of prophylactic treatment. One-hundred-sixty-five children without known neurological disorder who presented with their first febrile convulsion between the ages of six months and three years were assigned to daily phenobarbitone treatment or to a control group and followed up at a special clinic for six months. One-hundred-and-sixty-one-one children completed the trial, and of the 88 children assigned to phenobarbitone treatment 10 had further convulsions during this period compared with 14 of the 73 control children. Only 49 of those assigned to phenobarbitone took the drug regularly throughout the trial, and four of these had further febrile convulsions, a proportion not significantly different from that in the controls. All four had mean plasma phenobarbitone concentrations over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours of the repeat convulsion. Regular phenobarbitone does not seem to prevent febrile convulsions. Attention should instead be directed to organising emergency services to allow early termination of fevrile convulsions, whether first or subsequent, to prevent irreversible brain damage. To evaluate the efficacy of different antipyretic agents and their highest recommended doses for preventing febrile seizures.
                Randomized, placebo-controlled, double-blind trial.
                Five hospitals, each working as the only pediatric hospital in its region.
                A total of 231 children who experienced their first febrile seizure between January 1, 1997, and December 31, 2003. The children were observed for 2 years.
                All febrile episodes during follow-up were treated first with either rectal diclofenac or placebo. After 8 hours, treatment was continued with oral ibuprofen, acetaminophen, or placebo.
                Recurrence of febrile seizures.
                The children experienced 851 febrile episodes, and 89 of these included a febrile seizure. Febrile seizure recurrences occurred in 54 of the 231 children (23.4%). There were no significant differences between the groups in the main measure of effect, and the effect estimates were similar, as the rate was 23.4% (46 of 197) in those receiving antipyretic agents and 23.5% (8 of 34) in those receiving placebo (difference, 0.2; 95% confidence interval, -12.8 to 17.6; P = .99). Fever was significantly higher during the episodes with seizure than in those without seizure (39.7 degrees C vs 38.9 degrees C; difference, 0.7 degrees C; 95% confidence interval, -0.9 degrees C to -0.6 degrees C; P < .001), and this phenomenon was independent of the medication given.
                Antipyretic agents are ineffective for the prevention of recurrences of febrile seizures and for the lowering of body temperature in patients with a febrile episode that leads to a recurrent febrile seizure. Phenobarbital, once widely prescribed to prevent febrile seizures, is now in disfavor because of its side effects and lack of efficacy. Diazepam, administered only during episodes of fever, may be a safe, effective agent to prevent the recurrence of febrile seizures.
                We conducted a randomized, double-blind, placebo-controlled trial among 406 children (mean age, 24 months) who had at least one febrile seizure. Diazepam (0.33 mg per kilogram of body weight) or placebo was administered orally every eight hours during all febrile illnesses.
                During a mean follow-up of 1.9 years (a period during which 90 percent of febrile seizures recur), our intention-to-treat analysis showed a reduction of 44 percent in the risk of febrile seizures per person-year with diazepam (relative risk = 0.56; 95 percent confidence interval, 0.38 to 0.81; P = 0.002). A survival analysis of the length of time to the first recurrent febrile seizure did not show a significant difference between the treatment groups (P = 0.064 by the log-rank test), but after adjustment for covariates, diazepam was found to have a benefit (P = 0.027 by Cox regression analysis). An analysis restricted to children who had seizures while actually receiving the study medication (7 in the diazepam group and 29 in the placebo group) showed an 82 percent reduction in the risk of febrile seizures with diazepam (relative risk = 0.18; 95 percent confidence interval, 0.09 to 0.37; P < 0.001). Of the 153 children who took at least one dose of diazepam, 39 percent had ataxia, lethargy, or irritability or at least one other moderate side effect that was reversed after a reduction in the dose. There were no severe side effects.
                Oral diazepam, given only when fever is present, is safe and reduces the risk of recurrent febrile seizures. Psychometric tests were performed on 50 children with a history of febrile convulsions. Twenty-five of these had received daily phenobarbital for a mean of 35 months; 25 had received no phenobarbital. The two groups were matched for sex, age at the time of testing, race, and socioeconomic status. The tests used were the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), the Matching Familiar Figures Test, and the Children's Embedded Figures Test. There were no significant differences in test results between the two groups. A group of 355 children who were seen after a first febrile convulsion at the Kaiser Foundation Foundation Hospitals in Southern California from 1970 to 1975 were randomly assigned to three treatment groups-daily phenobarbital, "intermittent" phenobarbital given at the onset of fever, and no phenobarbital. We found that 42% had a relative with a febrile seizure and 16% a relative with an afebrile convulsion. 13% had seizures which were either lateralized or longer than ten minutes. Parents were unaware of the fever prior to the seizure in about 30% of the cases. In 81% the preseizure duration of fever was less than 24 hours. The mean follow-up was 28 months, with a range of 6 to 70 months. There was no significant difference in the recurrence rate between children receiving "intermitent" as compared with no phenobarbital. The recurrence rate in children receiving daily phenobarbital was significantly decreased compared to either of the other two groups. Severe recurrent febrile seizures occurred in no children on daily phenobarbital and in 4.4% of the children receiving either intermittent or no phenobarbital. Parental resistance, compliance, and reversible hyperactivity were the main problems encountered with the continuous phenobarbital regimen. Acetaminophen and low doses of diazepam were evaluated for the prevention of recurrences of febrile seizures in a placebo-controlled, double-blind trial. Children after their first febrile seizure were assigned to receive either one dose of rectally administered diazepam, and then, after 6 hours, oral doses of 0.2 mg/kg three times a day for the first 2 days if the fever stayed greater than 38.5 degrees C, or a placebo similarly during forthcoming febrile episodes. In addition, each febrile episode was randomly assigned to be treated with acetaminophen or the placebo. Thus four groups were examined for 2 years: patients receiving two kinds of placebo, patients receiving diazepam and a placebo, patients receiving acetaminophen and a placebo, and patients receiving both diazepam and acetaminophen. Of a total of 180 patients (102 boys), 161 were followed for the 2-year period and 157 were seen at the last outpatient examination: 80 in the diazepam group and 77 in the placebo group. The final analysis of the efficacy of the drugs was made on the basis of the data from 153 patients who had had at least one febrile episode during follow-up. There were 641 fever events during this period, and 38 children (21.1%) had 55 recurrences of febrile seizures. Acetaminophen had no effect on the recurrence rate. Seizures recurred at least once in 21 patients (28.4%) receiving diazepam and 17 (21.5%) receiving a placebo (p = 0.4138, log-rank test). The combination of antipyretic agents with anticonvulsant medication did not reduce the recurrence of febrile seizures. Our results show that low doses of acetaminophen or diazepam or both are ineffective for preventing febrile seizures. Phenobarbital is widely used in the treatment of children with febrile seizures, although there is concern about possible behavioral and cognitive side effects. In 217 children between 8 and 36 months of age who had had at least one febrile seizure and were at heightened risk of further seizures, we compared the intelligence quotients (IQs) of a group randomly assigned to daily doses of phenobarbital (4 to 5 mg per kilogram of body weight per day) with the IQs of a group randomly assigned to placebo. After two years, the mean IQ was 7.03 [corrected] points lower in the group assigned to phenobarbital than in the placebo group (95 percent confidence interval, -11.52 to -2.5, P = 0.0068 [corrected]). Six months later, after the medication had been tapered and discontinued, the mean IQ was 5.2 points lower in the group assigned to phenobarbital (95 percent confidence interval, -10.5 to 0.04, P = 0.052). The proportion of children remaining free of subsequent seizures did not differ significantly between the treatment groups. We conclude that phenobarbital depresses cognitive performance in children treated for febrile seizures and that this disadvantage, which may outlast the administration of the drug by several months, is not offset by the benefit of seizure prevention. A randomized double blind placebo controlled trial was carried out to study the effect of phenobarbitone (PB) in preventing recurrences of simple and atypical febrile convulsions among children in the age group 6 months to 6 years. Children with simple febrile convulsions were randomly allocated to receive either phenobarbitone or placebo. Children with atypical convulsions were treated with phenobarbitone, as a third group. Thirty children were admitted in each group. All the children were followed up for a period of twelve months. Recurrence of convulsions and side effects of PB were recorded. Recurrence occurred in only 7% (95% confidence interval: 1-22) of children on Phenobarbitone, suffering from either simple or atypical febrile convulsions, compared to 53% (95% confidence interval: 34-72) of children on placebo, suffering from simple febrile convulsions. With Phenobarbitone, 5% of children had intolerable side effects. These results suggest that long term prophylaxis with phenobarbitone, even in simple febrile convulsions will be useful. Of the 265 children aged between 6 and 18 months admitted to hospital in a 26-month period each with his first febrile convulsion, there were 64 who satisfied our criteria for a simple febrile convulsion. Of these, 43 (random) were entered into a double-blind trial of continuous sodium valproate versus phenobarbitone, and 21 were untreated. The dosage was phenobarbitone 3-6 mg/kg per day; sodium valproate 30-60 mg/kg per day. 39 completed treatment (21 phenobarbitone, 18 sodium valproate), 2 in each group being withdrawn because of unacceptable side effects. Close supervision and random serum drug estimations showed compliance to be good. After a mean treatment period of 12 months (mean age 25 months) there had been one recurrence in the sodium valproate group compared with 7 in the untreated group (P less than 0.05), and 4 recurrences in the phenobarbitone group. The difference between treatment and no treatment was significant (P less than 0.05). These results suggest that in simple febrile convulsions occurring between 6 and 18 months of age sodium valproate is as effective as phenobarbitone in preventing recurrence and that either treatment is better than none. nan nan To compare the effectiveness of intermittent clobazam versus diazepam therapy in preventing the recurrence of febrile seizures and assess adverse effects of each drug.
                This prospective randomized controlled trial was performed on neurologically normal children aged from 6 months to 5 years with a history of simple febrile seizures and normal electroencephalogram without any evidence of acute central nervous system infection. The patients were randomly prescribed with oral clobazam (37 cases) or diazepam (35 cases) when they developed a febrile disease. They were advised to use the medications during the first 48 h of the onset of fever. All the patients were monitored regarding developing seizure and adverse effects of the drugs. All patients were followed for 12 months.
                Overall, 243 episodes of fever occurred during the period, including 116 episodes in the clobazam group and 127 episodes in the diazepam group. Recurrence of seizures occurred in 2 (1.7%) subjects in the clobazam group, and in 4(3.1%) cases in the diazepam group. (P value=0.474). Twenty cases (54%) in the diazepam group and 5 (14.2%) cases in the clobazam group developed drowsiness and sedation during the follow-up period (P value=0.0001).
                Intermittent clobazam therapy seems advantageous to diazepam due to similar efficacy but significantly lower adverse effects such as drowsiness and sedation. A total of 107 children who had been hospitalized following a febrile convulsion were enrolled into the trial. By random allocation, 55 children were treated with pyridoxine hydrochloride (20 mgs twice daily) and the remaining 52 children were treated with a placebo until there had been either a further convulsion or a year had passed without recurrence. Eighty children were adequately followed up and of these, 17 had a recurrent febrile convulsion while receiving medication. Recurrences occurrences occurred in 7 of the 38 children receiving pyridoxine and in 10 of the 42 children receiving placebo (X2 = .346, p greater than 0.5). Initial tryptophan load tests had been abnormal in 34 children, and of these, recurrences occurred in 3 of the 17 who received pyridoxine and in 3 of the 17 who received placebo. It has yet to be shown that pyridoxine supplementation protects children from recurrent febrile convulsions. The relationship between the number of febrile episodes and recurrent febrile convulsions was studied prospectively in 289 children after their first febrile seizure. They were randomized to either short-term diazepam prophylaxis (n = 152) or to no prophylaxis (n = 137), and followed for 18 months. Among untreated children with many subsequent febrile episodes (greater than or equal to 4 per year) 29 of 37 (78%) had a recurrence vs. 17 of 100 (17%) with only few (less than 4 per year) feverish illnesses. The former group had a 4:1 chance of developing further febrile fits, compared with a 1:4 chance in the latter (P less than 0.0001). A similar pattern was observed in the prophylaxis group, but less recurrences were seen (30% vs. 6%, P less than 0.0001). By Cox regression analysis, the subsequent occurrence of many febrile episodes could be identified among several items, including young age at onset, as the adverse factor most highly associated with further febrile fits (P less than 0.0001). nan Cognitive and behavioral effects of phenobarbital in toddlers were assessed in a randomized, placebo-controlled study of patients who had had a febrile seizure. There were no significant differences in IQ (Binet or Bayley Scales) between placebo and phenobarbital groups after eight to 12 months of therapy. However, detrimental effects of phenobarbital were found in memory, for which serum level influenced scores, and in comprehension, in that length of treatment time affected performance. Hyperactivity was not seen. Behavioral changes, reported by parents, were increased fussiness and a characteristic disturbance of sleep. These changes varied in severity and were classified as transient, dose related, or unacceptable. After 12 months in the study, most parents could not distinguish between phenobarbital and placebo. Our data suggest that although most toddlers do not have major side effects from phenobarbital therapy when treated for a year, serum levels and length of time on phenobarbital should be kept at a minimum to reduce negative cognitive and behavioral effects. The purpose of this study was to compare three different modes of treatment in the prevention of relapses of febrile convulsions (Phenobarbital = PH, Sodium Valproate = SV, Placebo = PO) in a randomized therapeutic trial. The patients included in the study had shown their first generalized convulsive seizure during a bout of fever (greater than or equal to 38.5 degrees C) and were aged between 6 months and 4 years. They were subsequently followed up as outpatients, and Phenobarbital and sodium valproate levels were measured regularly to ascertain compliance with the treatment and to adjust the dosage accordingly. The patients' families were questioned with respect to the occurrence of feverish bouts and convulsive seizures during the interval between visits, as well as possible adverse reactions. An EEG was carried out yearly. Results were as follows: - 69 patients - 35 boys and 34 girls - with an average age of 24 months were divided into 3 groups according to treatment: 21 cases on PH, 22 cases on SV, and 26 cases on PO. - they were followed up for an average duration of 21 months. - the average number of feverish bouts per child and per year was evaluated at 2.5, no statistically significant difference being noticeable between the various modes of prophylaxis. - 15 relapses of febrile seizures were noted in 14 children, over an average duration of 23 months; on average, relapses occurred after 9 months; among the 14 children who had relapsed, one had been treated with SV, 4 with PH and 9 with PO, leading to estimated relapse rates of 4%, 19%, and 35% respectively. There is a statistically significant difference in the relapse rates between the treated groups (SV and PH) and the Placebo group, and a particularly significant difference between Sodium Valproate and Placebo.(ABSTRACT TRUNCATED AT 250 WORDS) In an open, prospective, randomized, and hospital-based study, comprising 219 consecutive children, 169 were given intermittent prophylaxis for one year, receiving either diazepam or valproic acid after their first febrile convulsion. Children admitted on odd dates (n = 89) were given rectal diazepam in solution every 12 h, whenever the temperature was 38.5 degrees C or more. Children admitted on even dates (n = 80) were given valproic acid as suppositories at times of fever. Twenty-three children in the diazepam group had a recurrence within 1 year versus 14 in the valproic acid group. On an intention-to-treat basis the 12-month recurrence rates in the 2 groups were similar, 27% vs 20%. The latter is well below figures for untreated controls from Denmark (32%), suggesting that intermittent valproic acid at times of fever may be effective, but further studies are needed. The number of complex recurrences, however, were significantly higher in the valproic acid group than in the diazepam group. Parental non-compliance was a major problem, and in the 2 study groups only 5 and 12 children, respectively, with recurrences were treated adequately. Sixty-nine children receiving diazepam had side-effects vs 37 receiving valproic acid. None were serious. In order to evaluate the effectiveness of diazepam for the reduction in the recurrence of febrile seizures we carried out a prospective study in two groups of children; Group A: 45 children (25 female, 20 male), receiving oral prophylaxis with diazepam, and Group B: 65 children (35 female, 30 male) who did not receive any oral prophylaxis. All subjects of both groups were followed for at least 4 years and finally re-evaluated at the mean age of 6.7+/-1.4 years. Among the patients of Group A, recurrent febrile seizures (FS) occurred in five of the 45 children (11.1%). Among the 65 children of Group B, 20 (30.7%) went on to have one or more additional episodes. In conclusion, our study demonstrates that oral diazepam, given only when fever is present, is an effective means of reducing the risk of recurrences of FS. The effect of phenobarbital on total sleep time, night awakenings, and lengthy awakenings was examined as part of a randomized trial of children with febrile seizures; information about sleep patterns was gathered by parental observation. Children were between ages 8-36 months at enrollment and were examined subsequently for 2 1/2 years. Night awakenings were not more common in children assigned to phenobarbital except for those who were poor sleepers at the beginning of the study. Total sleep time was no different in children assigned to phenobarbital than in those assigned to placebo. It is concluded that sleep problems reported in most young children with febrile seizures treated with phenobarbital did not exceed those reported in children treated with placebo, but a subset of predisposed children did experience an increase in night awakenings. Febrile seizures recur frequently. Factors increasing the risk of febrile seizure recurrence include young age at onset, family history of febrile seizures, previous recurrent febrile seizures, time lapse since previous seizure <6 months, relative low temperature at the initial seizure, multiple type initial seizure, and frequent febrile illnesses. Prevention of seizure recurrences serves two useful purposes: meeting parental fear of recurrent febrile seizures in general and reducing the (small) risk of a long-lasting and eventually injurious recurrent seizure. In daily practice, children with febrile seizures often are treated with antipyretics during fever to prevent febrile seizure recurrences. Thus far, no randomized placebo-controlled trial has been performed to assess the efficacy of intermittent antipyretic treatment in the prevention of seizure recurrence.
                We performed a randomized, double-blind, placebo-controlled trial. Children 1 to 4 years of age who had had at least one risk factor for febrile seizure recurrence were enrolled. They were randomly assigned to either ibuprofen syrup, 20 mg/mL, 0.25 mL (= 5 mg) per kilogram of body weight per dose, or matching placebo, to be administered every 6 hours during fever (temperature, >/=38.5 degrees C). Parents were instructed to take the child's rectal temperature immediately when the child seemed ill or feverish and to promptly administer the study medication when the temperature was >/=38.5 degrees C. Doses were to be administered every 6 hours until the child was afebrile for 24 hours. The parents were instructed not to administer any other antipyretic drug to the child. For measuring rectal temperature, a Philips HP5316 digital thermometer (Philips, Eindhoven, The Netherlands) was distributed. During subsequent treatment of the fever episode, parents had to call the investigator at least once each day to notify the investigator in case of febrile seizure recurrence. The investigator could be contacted by parents 24 hours per day. The primary outcome was the first recurrence of a febrile seizure. Kaplan-Meier curves and Cox regression were used for the statistical analysis. The treatment effect on the course of the temperature was assessed using analysis of covariance, with temperature at fever onset as covariate. Two analyses were performed. In an intention-to-treat analysis, all first recurrences were considered regardless of study medication compliance. A per-protocol analysis was limited to those recurrences that occurred in the context of study medication compliance.
                Between October 1, 1994, and April 1, 1996, 230 children were randomly assigned to ibuprofen syrup (111 children) or placebo (119 children). Median follow-up time was 1.04 years (25th-75th percentiles; 0.7-1.8 years) in the ibuprofen group and 0.98 years (0.7-1.6 years) in the placebo group. Of all children, 67 had a first febrile seizure recurrence, with 31 in the ibuprofen group and 36 in the placebo group. The 2-year recurrence probabilities were 32% and 39%, respectively. The recurrence risk in the ibuprofen group was 0.9 (95% confidence interval: 0.6-1.5) times the recurrence risk in the placebo group (intention to treat). Adjustment for baseline characteristics did not affect the risk-reduction estimate. Of the 67 recurrences, 30 occurred in the context of study medication compliance (13 ibuprofen, 17 placebo). The per-protocol analysis, which was limited to these events, showed similar results. A significant reduction in temperature (0.7 degrees C) after fever onset in the ibuprofen group compared with the placebo group was demonstrated if all 555 fever episodes were considered. In the fever episodes with a seizure recurrence, a similar temperature increase was shown in both groups, with no significant difference between the intention-to-treat and the per-protocol analysis.
                (ABSTRACT TRUNCATED) The aim of this study was to evaluate the efficacy and tolerance of intermittent oral administration of diazepam during hyperthermia for reducing the recurrence of febrile seizure: 185 children, between 8 months and 3 years of age, with a first febrile seizure and normal neurologic development, were randomly assigned in a double-blind fashion to receive orally administered diazepam (0.5 mg/kg, then 0.20 mg/kg, every 12 hours) or placebo, whenever the rectal temperature was more than 38 degrees C. The main criterion of efficacy was the seizure recurrence rate 1 year after the first seizure. The duration of the study was 3 years; eight different centers in France participated. There were 462 febrile episodes and 1000 days with prophylactic treatment. The recurrence rates did not differ between the diazepam group (16%) and the placebo (19.5%) group. The children with recurrent seizures were significantly younger at the time of the first seizure (17 +/- 6.9 months) than children without a recurrent seizure (21 +/- 8.5 months). In children with recurrent seizures, prophylactic treatment was correctly administered to only 1 of 15 children in the diazepam group and to 7 of 18 children in the placebo group. The following were the reasons for this poor cooperation: convulsion being the first manifestation of the fever (seven cases in each group), parents neglecting to give treatment (nine cases), and refusal to take treatment by two children. Side effects were similar in the two groups except for hyperactivity, which was more frequent in the diazepam (138 days) than in the placebo (34 days) group. Intermittent oral administration of diazepam at the onset of fever offered no advantage over placebo in preventing recurrence of seizure. This finding probably reflects a lack of efficacy of the intermittent method rather than of diazepam itself. Of 109 children treated daily with phenobarbital following the first fibrile convulsion, 42% developed a behavior disorder, usually hyperactivity. Daily phenobarbital therapy was prematurely discontinued in 54% of the children with behavior abnormality (20% of those treated). The behavior disturbance usually appeared within several months, was no correlated with high blood barbiturate levels, disappeared in 73%, and improved in all children when barbiturate therapy was discontinued. No characteristics of the child, the initial febrile seizure, or recurrence of febrile seizures were significantly correlated with the occurrence of the behavior disorder except for behavioral abnormality preceding the initial febrile convulsion. Eighteen percent of the children who received no phenobarbital developed behavior disorder, most often hyperactivity. The behavior disturbance spontaneously disappeared in 52%. Among these children not given phenobarbital, the group with normal behavior had a greater frequency of family history of seizures, especially febrile convulsions, and a lower frequency of preseizure behavior disturbance; abnormalities of pregnancy, labor, delivery, and neonatal period; delayed milestones; long seizures; abnormal results of neurological examination; abnormal EEG; and recurrent febrile seizures. We previously reported that IQ was significantly lowered in a group of toddler-aged children randomly assigned to receive phenobarbital or placebo for febrile seizures and there was no difference in the febrile seizure recurrence rate. We retested these children 3-5 years later, after they had entered school, to determine whether those effects persisted over the longer term and whether later school performance might be affected. On follow-up testing of 139 (of the original n = 217) Western Washington children who had experienced febrile seizures, we found that the phenobarbital group scored significantly lower than the placebo group on the Wide Range Achievement Test (WRAT-R) reading achievement standard score (87.6 vs 95.6; p = 0.007). There was a nonsignificant mean difference of 3.71 IQ points on the Stanford-Binet, with the phenobarbital-treated group scoring lower (102.2 vs 105.7; p = 0.09). There were five children in our sample with afebrile seizures during the 5-year period after the end of the medication trial. Two had been assigned to phenobarbital, and three had been in the placebo group. We conclude there may be a long-term adverse cognitive effect of phenobarbital on the developmental skills (language/verbal) being acquired during the period of treatment and no beneficial effect on the rate of febrile seizure recurrences or later nonfebrile seizures.
No clinically important benefits for children with febrile seizures were found for intermittent oral diazepam, phenytoin, phenobarbitone, intermittent rectal diazepam, valproate, pyridoxine, intermittent phenobarbitone or intermittent ibuprofen, nor for diclofenac versus placebo followed by ibuprofen, acetominophen or placebo. Adverse effects were reported in up to 30% of children. Apparent benefit for clobazam treatment in one recent trial needs to be replicated to be judged reliable. Given the benign nature of recurrent febrile seizures, and the high prevalence of adverse effects of these drugs, parents and families should be supported with adequate contact details of medical services and information on recurrence, first aid management and, most importantly, the benign nature of the phenomenon.