Effect of divalproex-lamotrigine combination therapy in frontal lobe seizures

Arch Neurol. 2001 Aug;58(8):1264-8. doi: 10.1001/archneur.58.8.1264.


Context: Patients with intractable frontal lobe seizures represent a difficult subclass of patients with epilepsy. When medications fail, surgical outcomes typically have not been as successful as medial temporal lobe resections. The combination therapy of valproic acid (divalproex sodium) and lamotrigine has shown promising results in patients with uncontrolled seizures.

Objective: To determine outcome in patients with intractable frontal lobe seizures who were treated with the combination of divalproex and lamotrigine.

Design: A nonrandomized, open-label, add-on trial.

Setting: Outpatients evaluated and treated at a tertiary care referral facility.

Patients: Twenty-one patients between 16 and 65 years old were studied. Patients were required to have failed at least 3 prior trials with antiepilepsy drugs. Criteria for frontal lobe onset included 1 or more of the following: frontal lesion on scan, positive ictal single-photon emission computed tomographic scan, symptoms consistent with frontal lobe onset, or an electroencephalogram (surface or invasive) consistent with frontal lobe onset.

Intervention: Patients were treated with divalproex-lamotrigine combination therapy for 1 year.

Main outcome measures: The main outcome measured was seizure reduction. Safety and tolerability were also evaluated.

Results: Four patients discontinued therapy. Ten of the remaining 17 became completely free of seizures. Two rashes occurred, but did not lead to discontinuation of therapy. The most common adverse events were tremor and weight gain.

Conclusion: Divalproex-lamotrigine combination therapy is a reasonable alternative in intractable frontal lobe epilepsy.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / therapeutic use*
  • Drug Therapy, Combination
  • Epilepsy, Frontal Lobe / drug therapy*
  • Epilepsy, Frontal Lobe / physiopathology
  • Female
  • Humans
  • Lamotrigine
  • Male
  • Middle Aged
  • Triazines / therapeutic use*
  • Valproic Acid / therapeutic use*


  • Anticonvulsants
  • Triazines
  • Valproic Acid
  • Lamotrigine