Front. Public Health, 13 September 2013 |

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

  • 1Arkansas Children’s Hospital Research Institute, Little Rock, AR, USA
  • 2Rossignol Medical Center, Irvine, CA, USA
  • 3University of Louisville, Louisville, KY, USA
  • 4Autism Recovery and Comprehensive Health Medical Center, Franklin, WI, USA
  • 5Autism Research Institute, San Diego, CA, USA
  • 6New York University Brain Research Laboratory, New York, NY, USA
  • 7MIND Research Network, University of New Mexico, Albuquerque, NM, USA
  • 8Hardy Healthcare Associates, Hingham, MA, USA
  • 9University of Minnesota Medical School, Minneapolis, MN, USA
  • 10University of Western Ontario, London, ON, Canada
  • 11Arizona State University, Tempe, AZ, USA

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 gluten-free 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.

Keywords: anti-epileptic drugs, autism spectrum disorder, epilepsy, gluten-free casein-free diet, ketogenic diet, seizures, treatment

Citation: Frye RE, Rossignol D, Casanova MF, Brown GL, Martin V, Edelson S, Coben R, Lewine J, Slattery JC, Lau C, Hardy P, Fatemi SH, Folsom TD, MacFabe D and Adams JB (2013) A review of traditional and novel treatments for seizures in autism spectrum disorder: findings from a systematic review and expert panel. Front. Public Health 1:31. doi: 10.3389/fpubh.2013.00031

Received: 21 April 2013; Paper pending published: 29 May 2013;
Accepted: 20 August 2013; Published online: 13 September 2013.

Edited by:

Ilknur Aydin Avci, Ondokuz Mayis University, Turkey

Reviewed by:

Satinder Aneja, Lady Hardinge Medical College, India
Clara van Karnebeek, The University of British Columbia, Canada

Copyright: © 2013 Frye, Rossignol, Casanova, Brown, Martin, Edelson, Coben, Lewine, Slattery, Lau, Hardy, Fatemi, Folsom, MacFabe and Adams. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Richard E. Frye, Arkansas Children’s Hospital Research Institute, Slot 512-41B, Room R4025, 13 Children’s Way, Little Rock, AR 72202, USA e-mail: