Autism

Autism

Autism spectrum disorder (ASD) is a complex, debilitating neurodevelopmental disorder with high heterogeneity. It is a lifelong disorder that has been increasing in prevalence worldwide and appears to have no clear common cause. To date, no cure is available, but several drugs, in particular risperidone and aripiprazole, are used to treat comorbid challenging behaviors in children with ASD. Treatment with risperidone and aripiprazole is currently recommended by the food and drug administration (FDA) for children five years and six years and older, respectively. Autism spectrum disorder (ASD) is a complex, debilitating neurodevelopmental disorder with high heterogeneity. The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), replaced the following previous categories: autism, Asperger’s disorder, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified by ASD1. The symptoms of ASD usually manifest between two and three years of age. Patients with ASD are all unique in their presentation. The disorder is characterized by core symptoms that include impairments in social interaction and communication, as well as the presence of restricted and repetitive behaviors. These symptoms are universal regardless of culture, race, ethnicity, or socioeconomic group1. All children with ASD experience difficulty in developing social, speech, and behavioral skills, therefore, early intervention with behavioral therapy affords the best opportunity to support healthy development and to deliver benefits across the life span. This, in combination with pharmacological therapies, if needed, will help patients function in their daily activities2,3,58.

ASD is a lifelong condition that severely impairs social skills and autonomy to a variable extent. A longitudinal study over 40 years has shown general improvement in symptoms into young adulthood, but poor outcomes in later adulthood4. Although core domains may improve across the life span, some symptom subdomains, such as limited interests or facial expression, may be more stable over time5,6. The impact of these long-term deficits on functioning is severe, with manifestations that tend to get increasingly complex later in life7. In 2018, the Centers for Disease Control and Prevention (CDC) determined that approximately one in 59 children is diagnosed with ASD, one in 37 boys and one in 151 girls, with increasing prevalence year after year8.

Unfortunately, the current evidence-based pharmacological treatment for ASD is limited to the treatment of comorbid challenging behaviors12. Risperidone and aripiprazole were approved by the FDA in 2006 and 2009, respectively, to treat irritability associated with autism13,14. The recommended age to start these medications is five years and above for risperidone and six years and above for aripiprazole. In randomized controlled trials, risperidone and aripiprazole have been found to improve irritability and agitation in children with ASD15,16. The majority of children with ASD show improvement in challenging comorbid behaviors such as irritability, agitation, aggression, self-injury, and disruptive behaviors when using these medications17. Both drugs are classified as atypical antipsychotics, and this class of medication can cause significant side effects like sedation, weight gain, and may affect the metabolism18. To decrease the medication-induced weight gain, metformin can be prescribed18,19. A few medications that are typically used for children with attention deficit hyperactivity disorder (ADHD), including methylphenidate, atomoxetine, and guanfacine have been reported to improve hyperactivity and attention symptoms in children with ASD as well20-22.

Altered neuronal connectivity and plasticity in the brain cortex has been reported to be the underlying cause for the signs and symptoms seen in ASD patients38-41. The prefrontal cortex has been suggested to be the main site of brain pathology in mice with ASD42-45. Aman et al. reported a considerable improvement in irritability and maladaptive behavior in comparison to baseline, including core symptoms associated with autism, in ASD patients who had been exposed to risperidone for an average of 21 months46. Recent studies in mice showed that chronic administration of risperidone or aripiprazole improved the valproic acid-induced social interaction deficits and recognition memory impairment, as well as the reduction in dendritic spine density in the prefrontal cortex and hippocampus47,48. In addition, methylphenidate and atomoxetine were both found to improve the valproic acid-induced social deficits and recognition memory impairment in mice25. The financial and social burden for ASD is huge and expected to rise substantially8. For example, intensive behavioral interventions for children with ASD cost $40,000 to $60,000 per child in the USA in 20119. The lifelong cost of supporting an individual with ASD and intellectual disability is estimated to be $2.4 million in the USA and £1.5 million ($2.2 million) in the UK10. Residential care or supportive living accommodation during adulthood and individual productivity loss both contribute to the high costs10. Caring for Americans with autism cost society a staggering $268 billion per year in 2015, a number that has increased more than six-fold since 2006 and expected to rise to $461 billion by 2025 in the absence of more-effective interventions and support across the life span8,11.

We used DSM-V criteria for patients diagnosis and severity and CGI scale for baseline severity and improvement. The American Academy of Child and Adolescent Psychiatry (AACAP) in its 2014 autism practice parameters emphasized that the most important diagnostic step is the clinical diagnosis based on careful consideration of DSM-V criteria. Guidelines further emphasized that while there are many assessment Instruments for ASD like CARS ,ADOS,..etc, these instruments, if needed, should only supplement and shouldn’t replace, informed clinical judgment based on DSM-V criteria58. American Academy of Pediatric (AAP) in its latest autism clinical report published 2020 emphasized the importance of using the DSM-V criteria and definitions for clinical diagnosis of ASD. It further considered that the most critical element in ASD diagnosis is to inform the DSM-V diagnostic criteria. Severity ratings is not a quantifiable score and is based on the extent of social communication impairments and restricted, repetitive patterns of behavior and the resultant service needs of the individual and often reflects the impact of cognitive limitations59. The CGI scale offers an objective readily understood, practical measurement tool that can easily be applied in the clinical practice, even in a very busy clinical setting. It has two main features that makes it suitable for ASD patients and trials. There is scope for cross-comparison with the many other trials in which the CGI rating scale has been used in psychiatry, and it reflects general clinical severity and improvement even in quite small ASD studies.

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