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, Gregory L. Brown,Victoria Martin4, Stephen Edelson, Robert Coben, Jeffrey Lewine, John C. Slattery, Chrystal Lau, Paul Hardy,
S. Hossein Fatemi,Timothy D. Folsom, Derrick MacFabe and James B. Adams

full article in Frontiers in Public Health 13 September 2013

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.

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