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      Paradoxical Seizure Increases a Risk with Levetiracetam Add-on Therapy

      A DGReview of :"A paradoxical effect of levetiracetam may be seen in both children and adults with refractory epilepsy."
      Seizure

      01/03/2003
      By Alison Palkhivala


      Levetiracetam can be an effective and well-tolerated add-on treatment for intractable partial seizures, but paradoxical seizure increases are a risk in a minority of patients.

      K. O. Nakken and colleagues from The National Centre for Epilepsy, Sandvika, Norway, performed a prospective, uncontrolled trial in which levetiracetam was used as an add-on therapy in 78 adults and 44 children with intractable epilepsy.

      Baseline seizure frequency was measured for eight weeks, after which they began levetiracetam add-on therapy. Then, seizure frequency was assessed a second time, this time for eight months.

      Among 40 percent of adults and 20 percent of children, seizure frequency was reduced by more than 50 percent with levetiracetam add-on therapy. Among these patients, seven adults and three children became seizure-free.

      However, 18 percent of adults and fully 43 percent of children experienced a more than 25 percent increase in their seizure frequency with levetiracetam. This paradoxical effect included the development of status epilepticus in three adults and four children and occurred most frequently at higher doses and in mentally retarded patients during the first two months of treatment, although status epilepticus developed at five and seven months in two children.

      Aside from the paradoxical effects, levetiracetam therapy was well tolerated. The most commonly reported side effect -- seen in 18 percent of adults and seven percent of children -- was somnolence.

      According to the authors, levetiracetam is usually an effective and well-tolerated add-on treatment for intractable, partial onset seizures. However, to avoid paradoxical reactions, the drug should be initiated at a lower dose and dose escalation should occur more slowly than is currently recommended by the manufacturer. In children, doses over 20 mg/kg/day should be introduced with caution.
      Seizure 2003 Jan;12(1):42-46. "A paradoxical effect of levetiracetam may be seen in both children and adults with refractory epilepsy."

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