title: A review of traditional and novel treatments for seizures in autism spectrum disorder: findings from a systematic review and expert panel.
abstract: 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.
authors.affiliation: Arkansas Children's Hospital Research Institute , Little Rock, AR , USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Frye
authors.affiliation: Rossignol Medical Center , Irvine, CA , USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rossignol
authors.affiliation: University of Louisville , Louisville, KY , USA.
authors.forename: Manuel F
authors.initials: MF
authors.lastname: Casanova
authors.affiliation: Autism Recovery and Comprehensive Health Medical Center , Franklin, WI , USA.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Brown
authors.affiliation: Autism Recovery and Comprehensive Health Medical Center , Franklin, WI , USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Martin
authors.affiliation: Autism Research Institute , San Diego, CA , USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Edelson
authors.affiliation: New York University Brain Research Laboratory , New York, NY , USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Coben
authors.affiliation: MIND Research Network, University of New Mexico , Albuquerque, NM , USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lewine
authors.affiliation: Arkansas Children's Hospital Research Institute , Little Rock, AR , USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Slattery
authors.affiliation: Arkansas Children's Hospital Research Institute , Little Rock, AR , USA.
authors.forename: Chrystal
authors.initials: C
authors.lastname: Lau
authors.affiliation: Hardy Healthcare Associates , Hingham, MA , USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Hardy
authors.affiliation: University of Minnesota Medical School , Minneapolis, MN , USA.
authors.forename: S Hossein
authors.initials: SH
authors.lastname: Fatemi
authors.affiliation: University of Minnesota Medical School , Minneapolis, MN , USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Folsom
authors.affiliation: University of Western Ontario , London, ON , Canada.
authors.forename: Derrick
authors.initials: D
authors.lastname: Macfabe
authors.affiliation: Arizona State University , Tempe, AZ , USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Adams
keywords: anti-epileptic drugs; autism spectrum disorder; epilepsy; gluten-free casein-free diet; ketogenic diet; seizures; treatment