Intermittent prophylaxis in febrile convulsions: diazepam or valproic acid?

Abstract

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° 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.

Febrile seizure recurrence reduced by intermittent oral levetiracetam

“…In the control group, the ranges of FS onset age, FS course, and visiting age were 6-59, 0.5-43, and 12-79 months, respectively. The medians (Q 1 -Q 3 ) were 22 (13-30), 12 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), and 36 (25-45), respectively. The range of FS frequency before enrollment was 2-12 times.…”

“…Although phenobarbital, VPA, and primidone are considered effective in preventing the recurrence of FS when continuously administered,5 long-term treatment with such drugs is associated with a wide spectrum of adverse effects, including sedation, behavioral changes, gastrointestinal and hematologic toxicity, hypersensitivity reactions, and rare fatal hepatotoxicity with VPA in young children. Although the intermittent administration of benzodiazepines (e.g., diazepam and midazolam) at the onset of fever is effective in placebo-controlled trials,6 the effectiveness of this treatment is limited because sedative effects can mask the signs and symptoms of any evolving central nervous system infection 5,7,8. Considering that the potential toxicities associated with antiepileptic therapy outweigh the relatively minor risks associated with FS, the American Academy of Pediatrics does not recommend continuous antiepileptic therapy with phenobarbital or VPA and intermittent therapy with diazepam to prevent FS recurrences 9,5.…”

“…Although the intermittent administration of benzodiazepines (e.g., diazepam and midazolam) at the onset of fever is effective in placebo-controlled trials, 6 the effectiveness of this treatment is limited because sedative effects can mask the signs and symptoms of any evolving central nervous system infection. 5,7,8 Considering that the potential toxicities associated with antiepileptic therapy outweigh the relatively minor risks associated with FS, the American Academy of Pediatrics does not recommend continuous antiepileptic therapy with phenobarbital or VPA and intermittent therapy with diazepam to prevent FS recurrences. 5,9 If we can explore a drug that is not only effective in preventing FS recurrence but also safe, we can reduce the anxieties of parents/caregivers and the unnecessary wasting of medical resources.…”

Benzodiazepines in epilepsy: pharmacology and pharmacokinetics

“…In placebo‐controlled trials, rectal diazepam gel (doses of 0.2–0.5 mg/kg) reduced seizure recurrence in children, adolescents and adults who had clusters of repetitive seizures in a non‐medical or home setting (87–90). Rectally administered diazepam may also be effective for short‐term prophylaxis (at doses of 5–10 mg or 0.3–0.6 mg/kg in patients weighing <10 kg) in children prone to febrile seizures (91–93), and higher doses of rectal diazepam (20–30 mg) have been used in adult patients with drug‐resistant epilepsy who are prone to serial seizures (94, 95). Use of oral diazepam is not recommended for long‐term epilepsy treatment (76).…”

Acute Drug Administration in Epilepsy: A Review

“…Daugbjerg et al [18] compared the prophylactic effects of rectal DZP with VPA suppositories in a randomized study with inconclusive results which, however, did not indicate that VPA was ineffective.…”