Regular Article| Volume 10, ISSUE 8, P583-587, December 2001

Effect of levetiracetam in patients with epilepsy and interictal epileptiform discharges

      This paper is only available as a PDF. To read, Please Download here.


      The effect of acute treatment with the new antiepileptic drug (AED) levetiracetam (Keppra®) on the frequency of interictal epileptiform discharges (IEDs) was evaluated in a double-blind, placebo-controlled, crossover study with therapeutic drug monitoring and serial electroencephalographic (EEG) observations. Acute (500 mg twice daily) and chronic (individualized, 500–1000 mg twice daily) doses of levetiracetam were administered as an add-on to current AED treatment. Efficacy was tested by measuring the frequency of IEDs in EEG recordings and the number of seizures. A single acute dose of levetiracetam induced a reduction of IEDs in eight out of ten patients. During the acute phase, an insufficient number of seizures occurred for analysis. During chronic treatment over 8 weeks, seven patients showed a reduction in seizure frequency (responder rate), and one patient remained seizure free. No correlation was seen between levetiracetam levels and IED frequency. Doses of levetiracetam of up to 2000 mg/day were well tolerated, and no interactions were seen with concomitant AEDs.




        • Binnie C.D
        • Kasteleijn-Nolst Trenité D.G.A
        • De Korte R
        Photosensitivity as a model for acute antiepileptic drug studies.
        Electroencephalography and Clinical Neurophysiology. 1986; 63: 35-41
        • Milligan N
        • Richens A
        Methods of assessment of antiepileptic drugs.
        British Journal of Clinical Pharmacology. 1981; 11: 443-456
        • Walczak T.S
        • Jayakar P
        Interictal EEG.
        in: Engel Jr J Pedley T.A Epilepsy: A Comprehensive Textbook. Lippincott William & Wilkins, Philadelphia1999 Chapter 75: 831-848
        • Pedley T.A
        Interictal epileptiform discharges: discriminating characteristics and clinical correlations.
        Am J EEG Technol. 1980; 20: 101-119
        • Noachtar S
        • Binnie C
        • Ebersole J
        • et al.
        A glossary of terms most commonly used by clinical electroencephalographers for the report form of EEG findings.
        Supplements to Clinical Neurophysiology. 2000
        • Schmidt D
        The influence of antiepileptic drugs on the electroencephalogram: a review of controlled clinical studies.
        Electroencephalography and Clinical Neurophysiology. 1982; Suppl.36: 453-466
        • Booker H.E
        • Celesia G.G
        Serum concentrations of diazepam in subjects with epilepsy.
        Archives of Neurology. 1973; 29: 191-194
        • Buchthal F
        • Svensmark O
        • Simonsen H
        Relation of EEG and seizures to phenobarbital in serum.
        Archives of Neurology. 1968; 19: 567-572
        • Riehl J.L
        • McIntyre H.B
        A quantitative study of the acute effects of diphenylhydantoin on the electroencephalogram of epileptic patients.
        Neurology. 1968; 18: 1107-1112
        • Monaco F
        • Riccio A
        • Morselli P.L
        • Mutani R
        EEG, seizures and plasma level correlations in patients on chronic treatment with carbamazepine.
        Electroencephalography and Clinical Neurophysiology. 1980; 48: 51P
        • Rowan A.J
        • Binnie C.D
        • de Beer-Pawlikowski N.K.B
        • et al.
        Serial twenty-four-hour serum level monitoring in the study of sodium valproate.
        in: Parsonage M.J Caldwell A.D.S The Place of Sodium Valproate in the Treatment of Epilepsy. Academic Press, London1980: 115-122
        • Patsalos P.N
        Pharmacokinetic profile of levetiracetam: toward ideal characteristics.
        Pharmacology and Therapeutics. 2000; 85: 77-85
        • Klitgaard H
        • Matagne A
        • Gobert J
        • Wülfert E
        Evidence for a unique profile of levetiracetam in rodent models of seizures and epilepsy.
        European Journal of Pharmacology. 1998; 353: 191-206
        • Kasteleijn-Nolst Trenité D.G.A
        • Marescaux C
        • Stodieck S
        • Edelbroek P.M
        • Oosting J
        Photosensitive epilepsy: a model to study the effects of antiepileptic drugs. Evaluation of the piracetam analogue, levetiracetam.
        Epilepsy Research. 1996; 25: 225-230
        • Hills M
        • Armitage P
        The two-period cross-over clinical trial.
        British Journal of Clinical Pharmacology. 1979; 8: 7-20
        • Ajmone-Marsan C
        • Zivin L.S
        Factors related to the occurrence of typical paroxysmal abnormalities in the EEG records of epileptic patients.
        Epilepsia. 1970; 11: 361-381
        • Metrakos K
        • Metrakos J.D
        Genetics of convulsive disorders. II. Genetic and electroencephalographic studies in centrencephalic epilepsy.
        Neurology. 1961; 11: 474-483
        • Degen R
        • Degen H.E
        Some genetic aspects of idiopathic and symptomatic absence seizures: waking and sleep EEGs in siblings.
        Epilepsia. 1990; 31: 784-794
        • Villareal H.J
        • Wilder B.J
        • Wilmore L.J
        • Bauman A.W
        • Hammon E.J
        • Bruni J
        Effects of valproic acid on spike wave discharges in patients with absence seizures.
        Neurology. 1978; 28: 886-891
        • Bruni J
        • Wilder B.J
        • Bauman A.W
        • Wilmore L.J
        Clinical efficacy and long-term effects of valproic acid on spike and wave discharges.
        Neurology. 1980; 30: 42-46
        • Rowan A.J
        • Binnie C.D
        • Warfield C.A
        • Meinardi H
        • Meijer J.W.A
        The delayed effect of sodium valproate on the photoconvulsive response in man.
        Epilepsia. 1979; 20: 61-68