STATUS EPILEPTICUS ASSOCIATED WITH THE COMBINATION OF VALPROIC ACID AND CLOMIPRAMINE

An epileptic patient well controlled on valproic acid (VPA) developed a prolonged episode of status epilepticus 12 days after initiation of 75 mg of clomipramine (CMI) to treat depression. Serum level of VPA in the emergency room was unchanged from her previous levels; serum leve l of CMI was very elevated despite the relatively small dose of CMI. A pharmacokinetic interaction between VPA, an enzyme inhibitor, and CMI has,or been described but seemed to have occurred in this patient. De creased metabolism of CMI Ed its metabolites, increased free CMI fract ion, and precipitation of a nonlinear saturation kinetic stare has bee n described when CMI was used concomitantly with other highly protein- bound, enzyme inhibiting compounds. This case provides reasonable evid ence that the combination of VPA and CMI may result in elevation of le vels of CMI and possibly of its metabolites and may precipitate seizur es in patients with an underlying predisposition. The elevated serum l evel of CMI at the time of the seizures, despite the relatively small oral dose of the drug, suggests that VPA may have inhibited its metabo lism and/or elimination.