title: A paradoxical effect of levetiracetam may be seen in both children and adults with refractory epilepsy.
abstract: The aim of this prospective, uncontrolled clinical study was to evaluate the tolerability and the efficacy of levetiracetam as add-on treatment in 78 adults and 44 children with intractable epilepsy. The patients' seizure frequency in the 8 weeks baseline period was compared to their seizure frequency after a mean follow-up of 8 months of treatment.A greater than 50% reduction in seizure frequency was achieved in 31 adults (40%) and 9 children (20%), of whom 7 adults (9%) and 3 children (7%) became seizure free. Most often levetiracetam was well tolerated, somnolence being the most frequently reported side effect (18% in adults and 7% in children). However, in 14 adults (18%) and 19 children (43%) levetiracetam was associated with an increase (>25%) in seizure frequency. Such a paradoxical effect, including the development of status epilepticus in three adults and four children, appeared most often in mentally retarded patients during the first 2 months of treatment, and on relatively high doses. Two children developed status epilepticus after 5 and 7 months, respectively. In conclusion, levetiracetam is usually well tolerated as add-on treatment in patients with difficult-to-treat partial onset seizures. By using a lower initial dose and a slower dose escalation than recommended by the manufacturer, a paradoxical effect may perhaps be avoided. In children, doses >20 mgkg(-1) per day should be introduced with caution.
authors.affiliation: The National Centre for Epilepsy, Sandvika, Norway. karl.otto.nakken@epilepsy.no
authors.forename: Karl O
authors.initials: KO
authors.lastname: Nakken
authors.forename: Ann Sofie
authors.initials: AS
authors.lastname: Eriksson
authors.forename: Rasmus
authors.initials: R
authors.lastname: Lossius
authors.forename: Svein I
authors.initials: SI
authors.lastname: Johannessen
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D004351:Drug Resistance; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use*; D011446:Prospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam