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Medication

Medication Summary

The established therapies for ASD are nonpharmacologic. These therapies may include behavioral, educational, and psychological treatment. No pharmacologic agent is effective in the treatment of the core behavioral manifestations of ASD. However, medication may be effective in the treatment of comorbid disorders, including self-injurious behaviors and movement disorders.

Simultaneous treatment with two or more antipsychotics may be beneficial to treat agitation/irritability, physical aggression, and self-injurious behaviors of patients with ASD, particularly moderately to severely ill males with ASD and intellectual disability. Generally these treatment regimens are well tolerated without serious adverse events.^[199]

Class Summary

The atypical antipsychotic agents risperidone and aripiprazole have been approved by the FDA for irritability associated with ASD.

Risperidone (Risperdal, Risperdal Consta, Risperdal M-Tab)

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Risperidone is an atypical antipsychotic agent that is indicated for irritability associated with ASD in children and adolescents aged 5-16 years. Risperidone is a mixed serotonin-dopamine antagonist that binds to 5-HT2 with very high affinity and binds to the dopamine D2 receptor with less affinity. Affinity for the dopamine D2 receptor is 20 times lower than that for the 5-HT2 receptor. Risperidone is FDA approved for irritability and aggression in children with ASD, 5 years and older.

The combination of serotonin antagonism and dopamine antagonism is thought to improve negative symptoms of psychoses and reduce the incidence of extrapyramidal side effects in comparison with conventional antipsychotics.

Aripiprazole (Abilify, Abilify MyCite)

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Aripiprazole is indicated for irritability associated with ASD in children and adolescents aged 6-17 years. Aripiprazole is thought to be a partial dopamine (D2) and serotonin (5-HT1A) agonist, and to antagonize serotonin (5-HT2A). Aripiprazole is available as a tablet, an orally disintegrating tablet, or an oral solution.

Ziprasidone (Geodon)

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Ziprasidone, a second-generation antipsychotic drug, is used off-label to treat serious behavior disorders associated with ASD, such as self-injurious behavior. It elicits its effects through antagonism of D2, D3, 5-HT2A, 5-HT2C, 5-HT1A, 5-HT1D, and alpha1-adrenergic receptors. In addition, it has a moderate antagonistic effect for histamine H1. It moderately inhibits the reuptake of serotonin and norepinephrine.

Class Summary

SSRIs are widely prescribed for children with ASD. These agents are used off-label to help with intractable repetitive behaviors, such as compulsion.

Fluoxetine (Prozac)

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Fluoxetine selectively inhibits presynaptic serotonin reuptake, with minimal or no effect on the reuptake of norepinephrine and dopamine.

Citalopram (Celexa)

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Citalopram enhances serotonin activity by selective reuptake inhibition of serotonin at the neuronal membrane. Dose-dependent QT prolongation has been reported with citalopram.^{[149, 150]}. This agent is contraindicated in patients with congenital long QT syndrome.

Escitalopram (Lexapro)

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Escitalopram is an S-enantiomer of citalopram. The mechanism of action is thought to be potentiation of serotonergic activity in the central nervous system (CNS), resulting from the inhibition of CNS neuronal reuptake of serotonin.

Class Summary

Stimulants may be effective for treating hyperactivity associated with ASD. The magnitude of response, however, is less than that seen in developmentally normal children with attention deficit hyperactivity disorder

Methylphenidate (Ritalin, Quillivant XR, Ritalin LA, Concerta)

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Methylphenidate is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. Methylphenidate is a racemic mixture composed of the d- and l-enantiomers. The d-enantiomer is more pharmacologically active than the l-enantiomer.

Class Summary

Alpha-2-adrenergic agonists may facilitate the management of inattention, hyperactivity, and impulsivity in children with ASD.

Clonidine (Catapres, Catapres-TTS, Kapvay)

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Clonidine stimulates alpha-2-adrenoreceptors in the brain stem, activating an inhibitory neuron, which in turn results in reduced sympathetic outflow. These effects result in a decrease in vasomotor tone and heart rate. May aid in the treatment of agression in children and adolescents.

Guanfacine (Intuniv)

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Guanfacine, an alpha-2-adrenergic agonist, may preferentially bind postsynaptic alpha-2A adrenoreceptors in the prefrontal cortex, and this preferential binding may improve delay-related firing of prefrontal cortex neurons. As a result, guanfacine may affect behavioral inhibition. It has been used off label to reduce hyperactivity in children.

Questions

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Media Gallery

The significance of answers to individual Autism Screening Checklist items is as follows: Item 1- A "yes" occurs in healthy children and children with some pervasive developmental disorders; a "no" occurs in children with autism, Rett syndrome, and other developmental disorders. Item 2 - A "yes" occurs in healthy children, not children with autism. Item 3 - A "yes" occurs in healthy children and children with Asperger syndrome (ie, high-functioning autism); a "no" occurs in children with Rett syndrome; children with autism may elicit a "yes" or a "no"; some children with autism never speak; some children with autism may develop speech normally and then experience a regression with the loss of speech. Item 4 - A "yes" occurs in healthy children and children with Asperger syndrome and some other pervasive developmental disorders; a "no" occurs in children with developmental disorders; children with autism may elicit a "yes" or a "no." Items 5-10 - Scores of "yes" occur in some children with autism and in children with other disorders. Item 11 – A "yes" occurs in healthy children; a "no" occurs in some children with autism and in children with other disorders. Items 12, 13 - Scores of "yes" occur in some children with autism and in children with other disorders. Items 14-19 - Scores of "yes" occur in children with schizophrenia and other disorders, not in children with autism, Asperger syndrome, or other autism spectrum disorders. The higher the total score for items 5-10, 12, and 13 on the Autism Screening Checklist, the more likely the presence of an autism spectrum disorder.
Serotonin syndrome checklist.

of 2

Author

James Robert Brasic, MD, MPH, MS, MA Assistant Professor, Russell H Morgan Department of Radiology and Radiological Science and Neurology, Division of Nuclear Medicine and Molecular Imaging, Assistant Professor, Department of Neurology, Johns Hopkins University School of Medicine

James Robert Brasic, MD, MPH, MS, MA is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, American Academy of Neurology, International Parkinson and Movement Disorder Society, Society for Neuroscience, Society of Nuclear Medicine and Molecular Imaging

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Johns Hopkins University School of Medicine; New York City Health and Hospitals/Bellevue, New York University Langone Health<br/>Serve(d) as a speaker or a member of a speakers bureau for: Society of Nuclear Medicine and Molecular Imaging, Maryland Regional Council of Child and Adolescent Psychiatry<br/>Received research grant from: National Institutes of Health, Johns Hopkins University School of Medicine, Intellectual & Developmental Disabilities Research Center (U54 HD079123) at the Kennedy Krieger Institute<br/>Received income in an amount equal to or greater than $250 from: Gerson Lehrman Group; Guidepost<br/>Received royalty from Medscape for other.

Coauthor(s)

Ashley B Durbin, BS, BA

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Caroly Pataki, MD Health Sciences Clinical Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, David Geffen School of Medicine

Caroly Pataki, MD is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, New York Academy of Sciences, Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Additional Contributors

Farzaneh Farhadi, MD Postdoctoral Research Fellow, Johns Hopkins Hospital

Disclosure: Nothing to disclose.

Tarek Elshourbagy, MBBCh Intern, Kasr Alainy Medical School, Cairo University, Egypt; Research Physician, Department of Radiology, Johns Hopkins University School of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Acknowledgments

This publication was made possible by the Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR003098 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS or NIH. This research is also supported by the Radiology Bridge Funding Initiative to Stimulate and Advance Research (RAD BriteStar Bridge) Award of the Johns Hopkins University School of Medicine and the Intellectual and Developmental Disabilities Research Center (U54 HD079123) at the Kennedy Krieger Institute of Johns Hopkins Medical Institutions in Baltimore, Maryland.

Autism Spectrum Disorder Medication

Medication Summary

Second-Generation Antipsychotics

Class Summary

Risperidone (Risperdal, Risperdal Consta, Risperdal M-Tab)

Risperidone (Risperdal, Risperdal Consta, Risperdal M-Tab)

Aripiprazole (Abilify, Abilify MyCite)

Aripiprazole (Abilify, Abilify MyCite)

Ziprasidone (Geodon)

Ziprasidone (Geodon)

SSRI Antidepressants

Class Summary

Fluoxetine (Prozac)

Fluoxetine (Prozac)

Citalopram (Celexa)

Citalopram (Celexa)

Escitalopram (Lexapro)

Escitalopram (Lexapro)

Stimulants

Class Summary

Methylphenidate (Ritalin, Quillivant XR, Ritalin LA, Concerta)

Methylphenidate (Ritalin, Quillivant XR, Ritalin LA, Concerta)

Alpha-2-adrenergic agonists

Class Summary

Clonidine (Catapres, Catapres-TTS, Kapvay)

Clonidine (Catapres, Catapres-TTS, Kapvay)

Guanfacine (Intuniv)

Guanfacine (Intuniv)

Autism Spectrum Disorder Medication

Medication Summary

Second-Generation Antipsychotics

Class Summary

Risperidone (Risperdal, Risperdal Consta, Risperdal M-Tab)

Aripiprazole (Abilify, Abilify MyCite)

Ziprasidone (Geodon)

SSRI Antidepressants

Class Summary

Fluoxetine (Prozac)

Citalopram (Celexa)

Escitalopram (Lexapro)

Stimulants

Class Summary

Methylphenidate (Ritalin, Quillivant XR, Ritalin LA, Concerta)

Alpha-2-adrenergic agonists

Class Summary

Clonidine (Catapres, Catapres-TTS, Kapvay)

Guanfacine (Intuniv)

References

Tables

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