Recent advances in the treatment of ASD
Behavioral treatments. Behavioral modalities are first-line treatment interventions for ASDs. They improve language skills, cognitive abilities, adaptive behaviors, and social skills, and reduce aggression and anxiety.46 The earlier the initiation of behavioral interventions, the better. Increased brain plasticity in younger children may maximize treatment benefits; early altering of developmental trajectories may best improve outcomes and decrease the likelihood of severe problematic behaviors.47
The 2009 National Standards Report reviewed a wide range of nonpharmacological treatments for autism.48 Of 38 treatments investigated, 11 were found to have enough supporting evidence to qualify as “established” treatments substantiating favorable outcomes. These established treatments were all behavioral interventions, and several fell under the umbrella category of applied behavior analytic (ABA) therapy. ABA therapy is based on the science of understanding the laws by which environmental events influence and change behavior.
Discrete trial training (DTT) is perhaps the most common type of ABA therapy. It involves breaking down complex skills and teaching each subskill through a series of highly structured, massed teaching trials. Each trial consists of a precise and consistent instruction designed to elicit a specific response. Often, the sought-after response is an imitation of the therapist’s model or compliance with a verbal request. The response is shaped and reinforced with rewards contingent on the child’s production of the target response. One criticism of DTT is that because of the highly structured trials through which desired responses are learned, it may be difficult for individuals with ASDs to generalize the responses to the natural environment. In response, some therapists recommend other ABA techniques endorsed by the National Standards Project, including pivotal response training (PRT).
Although PRT is also based on a system of contingency rewards, it aims to provide interventions in the natural environment with the goal of shaping behavioral improvements that may be generalized across a variety of settings. Social skills groups and training (which may be employed using a wide variety of strategies, including PRT as well as peer mentoring, social stories, modeling, social problem solving, scripting procedures, computer-based interventions, self-monitoring, and others) are also widely used and accepted with varying levels of supporting research.49,50
Unfortunately, in contrast to the behavioral interventions mentioned earlier, there remain a significant number of treatments advertised to parents that have little peer-reviewed evidence to support their efficacy. These include hyperbaric oxygen treatment, chelation therapy, and stem cell therapies offered outside the United States. These treatments cannot only be extremely expensive, but they may also carry significant medical risks that parents and care providers may not always be informed of before initiating treatment.
Medications. Drugs may also play a role in treating individuals with ASDs and overlapping symptoms of other psychiatric disorders. For example, children with ASDs may have significant symptoms that overlap with ADHD, anxiety, obsessive-compulsive disorder, and/or mood disorders. Psychopharmacologic agents aimed at treating these conditions may also be used for individuals with ASDs.51 Among these agents, risperidone and aripiprazole are the only two FDA-approved for the treatment of ASD in children. Specifically, these two drugs are approved for the treatment of irritability and associated symptoms, such as aggression, self-injurious behaviors, and temper tantrums. However, serious adverse effects (weight gain, metabolic abnormalities, and tardive dyskinesia) are associated with these medications, so they should be used with caution. Furthermore, persons with ASDs or other developmental disabilities may be more sensitive to adverse effects of medications and may require slower titration schedules with lower target doses.
In the area of new and emerging treatments, N-acetylcysteine (NAC) is a safe, orally bioavailable prodrug of cysteine that is known for its role as an antidote against acetaminophen overdose.52 Cysteine supplied by NAC treatment can also be oxidized to cystine, a substrate for the glutamate-cystine antiporter that causes the reverse transport of nonvesicular glutamate into the extracellular space. This process ultimately stimulates the type 2/3 metabotropic glutamate receptors, inhibiting the vesicular release of glutamate and resulting in a decrease in glutamatergic neurotransmission and a reduced E:I ratio.53
The results from a pilot study of NAC (900 mg daily for 4 weeks, then 900 mg twice daily for 4 weeks, and finally 900 mg 3 times daily for 4 weeks) showed significant improvements on irritability and associated symptoms in children with ASD.54 On the basis of these data, a larger study will be conducted in hopes of replicating this result while examining the effect of NAC on glutamatergic transmission and glutathione metabolism.
While medications currently available for ASD do not treat the core symptoms of social and communication deficits or restricted interests and repetitive behaviors, ongoing research is aimed toward discovering such therapeutics. Oxytocin is an endogenous hormone that may increase the saliency of social stimuli and link the encoding of these stimuli to social reward and reinforcement.55 Intravenous oxytocin may reduce repetitive behaviors and increase retention of social cognition in patients with ASD.56,57 However, the intravenous route is not clinically attractive, and oxytocin’s poor blood-brain barrier penetration has limited its use. Researchers are attempting to circumvent this problem by administering the compound intranasally. It is hypothesized that intranasal administration of peptides allows for passage through clefts in the nasal epithelium into the cerebrospinal fluid.58 In a double-blind, randomized, placebo-controlled, crossover design, a single dose of oxytocin nasal spray was shown to improve recognition of others’ emotions by participants with ASD.59 In another study, participants with ASD given a single dose of intranasal oxytocin responded more strongly to others and exhibited more appropriate social behavior and affect.60 A single dose of intranasal oxytocin also significantly improved eye gaze frequency in a randomized, double-blind, placebo-controlled trial in teenagers with fragile X syndrome, a genetic syndrome known to be associated with an elevated prevalence (20% to 60%) of autistic symptoms.61