The Effect of Frusemide, Mexiletine, (+)‐propranolol and Three Benzodiazepine Drugs on Interictal Spike Discharges in the Electroencephalograms of Epileptic Patients

Abstract

I The effects of single intravenous doses of diazepam, clonazepam, lorazepam, frusemide, mexiletine and (+)-propranolol on the frequency of electroencephalographic (EEG) interictal spike discharges were assessed in three double-blind placebo-controlled trials in fourteen epileptic patients. 2 Diazepam (5 mg) produced a significant mean decrease of spike discharges to about one third of the control frequency. The effect developed rapidly and persisted for the duration of the study (up to 25 min after injection). A larger dose (10 mg) failed to produce a further reduction in the frequency of the spike discharges. 3 Clonazepam (0.5 mg), frusemide (40 mg) and lorazepam (2 mg) appeared to be as effective as diazepam in reducing spike discharges, although the effect of the latter drug seemed to develop with some delay. 4 Mexiletine (100 mg) and (+)-propranolol (50 mg) did not reduce paroxysmal EEG discharges, their effects being not significantly different from that of saline. 5 EEG spike counting after intravenous administration of single test-doses appeared to be both a simple and promising technique for the rapid preliminary evaluation of the clinical efficacy of new antiepileptic drugs.

The effect of lamotrigine, a novel anticonvulsant, on interictal spikes in patients with epilepsy.

“…In six patients with photosensitive epilepsy they demonstrated reduction of photoconvulsive Table 2 Mean serum concentration of diazepam (ng ml-') and lamotrigine (pLg ml[') (± s.d. ) (Ahmad et al, 1977;Mulligan et al, 1983), rectally (Milligan et al, 1982), and intramuscularly (Jawad et al, 1986). This study demonstrates that this technique, with proper modification, can be used to assess new anticonvulsant drugs that are only available as an oral preparation.…”

Acute effects of intravenous phenytoin on the frequency of inter‐ictal spikes in man.

“…10 min from the beginning of the injection. The EEGs were then code numbered and subsequently analysed blind and in random order using the method described by Ahmad et al (1977). The number of spikes in each 10 min EEG after treatment was counted and expressed as a percentage of that in 10 min of control EEG before treatment.…”

“…Several investigators have demonstrated a reduction of inter-ictal spikes following single doses of intravenous diazepam (Neidermeyer, 1970;Booker & Celesia, 1973) but Ahmad et al (1977) were the first to suggest that spike counting could be used for the short term assessment of new compounds given intravenously. By modifying the method of Ahmad et al.…”

“…Several investigators have demonstrated a reduction of inter-ictal spikes following single doses of intravenous diazepam (Neidermeyer, 1970;Booker & Celesia, 1973) but Ahmad et al (1977) were the first to suggest that spike counting could be used for the short term assessment of new compounds given intravenously. By modifying the method of Ahmad et al (1977) we have previously demonstrated the efficacy of single dose rectal administration of diazepam in reducing epileptiform abnormalities in the EEG (Milligan etal., 1982). Before this technique can be extended to new compounds a series of placebocontrolled studies are needed demonstrating the effectiveness of the established antiepileptic drugs in reducing the frequency of inter-ictal spikes, thus validating the technique.…”

Commission on Outcome Measurement in Epilepsy, 1994–1997: Final Report

“…The term surrogate in this context is used to indicate endpoints that do not involve changes in seizure activity but are considered predictive of seizure susceptibility. Examples include drug-induced changes in interictal epileptiform discharges in the EEG (76) or the photoparoxysmal response to intermittent photic stimulation (77). These follow-up).…”