A review of traditional and novel treatments for seizures in autism spectrum disorder: Findings from a systematic review and expert panel

Richard E. Frye, Daniel Rossignol, Manuel F. Casanova, Victoria Martin, Gregory L. Brown, Stephen Edelson, Robert Coben, Jeffrey Lewine, John C. Slattery, Chrystal Lau, Paul Hardy, S. Hossein Fatemi, Timothy D. Folsom, Derrick MacFabe, James B. Adams

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73 Scopus citations


Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases and by a panel of experts that treat ASD individuals. Only a few anti-epileptic drugs (AEDs) have undergone carefully controlled trials in ASD, but these trials examined outcomes other than seizures. Several lines of evidence point to valproate, lamotrigine, and levetiracetam as the most effective and tolerable AEDs for individuals with ASD. Limited evidence supports the use of traditional non-AED treatments, such as the ketogenic and modified Atkins diet, multiple subpial transections, immunomodulation, and neurofeedback treatments. Although specific treatments may be more appropriate for specific genetic and metabolic syndromes associated with ASD and seizures, there are few studies which have documented the effectiveness of treatments for seizures for specific syndromes. Limited evidence supports L-carnitine, multivitamins, and N-acetyl-L-cysteine in mitochondrial disease and dysfunction, folinic acid in cerebral folate abnormalities and early treatment with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence for a number of novel treatments, particularly magnesium with pyridoxine, omega-3 fatty acids, the glutenfree casein-free diet, and low-frequency repetitive transcranial magnetic simulation. Zinc and L-carnosine are potential novel treatments supported by basic research but not clinical studies.This review demonstrates the wide variety of treatments used to treat seizures in individuals with ASD as well as the striking lack of clinical trials performed to support the use of these treatments. Additional studies concerning these treatments for controlling seizures in individuals with ASD are warranted.

Original languageEnglish (US)
Article number31
JournalFrontiers in Public Health
Issue numberSEP
StatePublished - Sep 13 2013

Bibliographical note

Publisher Copyright:
© 2013 Frye, Rossignol, Casanova, Brown, Martin, Edelson, Coben, Lewine, Slattery, Lau, Hardy, Fatemi, Folsom, MacFabe and Adams.


  • Anti-epileptic drugs
  • Autism spectrum disorder
  • Epilepsy
  • Gluten-free casein-free diet
  • Ketogenic diet
  • Seizures
  • Treatment


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