Combined ketogenic diet and vagus nerve stimulation: rational polytherapy?

Epilepsia. 2007 Jan;48(1):77-81. doi: 10.1111/j.1528-1167.2006.00903.x.


Objective: The concept of "rational polypharmacy" has been associated with anticonvulsant management for decades, but the term has not been applied to nonpharmacologic therapies.

Methods: We conducted a multicenter, retrospective study of children who received concurrent diet (ketogenic or modified Atkins) and vagus nerve stimulation (VNS) treatment for medically intractable epilepsy.

Results: Thirty children in total from six epilepsy centers were treated over a 6-yr period. The median age at the initiation of combination therapy was 10 yr (range, 4-24 yr). Sixteen (53%) received dietary therapy followed by VNS; no differences were noted between centers. After 3 months, 21 (70%) had seizure reduced by >50% over the previous single nonpharmacologic treatment, of whom 13 (62%) had improvement within the first month. A 5-min VNS off-time correlated with >90% seizure reduction (p = 0.02). The median duration of nonpharmacologic polytherapy was 12 months (range, 0.5-96 months); 17 (57%) remain on dual therapy at this time. No side effects were noted. Most patients who discontinued combination therapy did so because of a lack of efficacy rather than restrictiveness.

Conclusions: In this small group, the combined use of diet and VNS appeared synergistic and yielded rapid benefits. It may be more effective with longer VNS off-times. Further prospective studies of this combination in refractory pediatric epilepsy are needed to help guide optimal use.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Diet, Carbohydrate-Restricted
  • Dietary Fats / administration & dosage*
  • Dietary Fats / metabolism*
  • Electric Stimulation Therapy / methods*
  • Epilepsy / diet therapy*
  • Epilepsy / metabolism
  • Epilepsy / therapy*
  • Evaluation Studies as Topic
  • Female
  • Humans
  • Ketosis / metabolism*
  • Longitudinal Studies
  • Male
  • Retrospective Studies
  • Treatment Outcome
  • Vagus Nerve / physiology*


  • Dietary Fats