Medication Summary

Many types of medications are used to address different behavioral issues and comorbid disorders associated with pervasive developmental disorder (PDD/ASD). For example, the US Food and Drug Administration (FDA) has approved risperidone and aripiprazole for use in children to treat irritability associated with autistic disorder.^{[42, 43, 44]}

Data from several large, randomized, placebo-controlled trials suggested that antipsychotic medications may be helpful, particularly for aggression. In addition, treatment with antipsychotics may improve restricted, repetitive, and stereotyped patterns of behavior and interests. However, no medications substantially change deficits in social interaction and communication.

The use of antipsychotic medications requires careful monitoring of weight, fasting lipid profile, and fasting plasma glucose as recommended by the consensus statement published in Diabetes Care.^[45]

Treatment of comorbid conditions such as ADHD and OCD may be indicated, although few research studies support the efficacy of the medications currently approved for use in children who are developing normally. Because FDA guidance is absent, child and adolescent psychiatrists target disruptive behaviors with the class of medications indicated by the symptom clusters.^[46]

Innovative treatments currently in the development phase include N-methyl-D-aspartate (NMDA) receptor (a type of glutamate receptor) blockers. A preliminary trial using a similar agent, amantadine, proved promising in a placebo-controlled trial.^[47]Inhibition of group 1 metabotropic glutamate receptor is being considered specifically in the use of individuals with Fragile X syndrome, because studies demonstrate that FMRP affects dendrite maturation via this neurotransmitter system.^[48]

Herbal and alternative treatments require more research. The most promising is melatonin, the hormone that regulates sleep. A pharmaceutical-grade, melatonin like compound, ramelteon, is available commercially. Children with ASD often have sleep disorder that may be ameliorated with melatonin.^[49] The most commonly prescribed sleep medications are melatonin followed by central alpha agonists.^[13]

Other herbal treatments should be carefully weighed like any traditional medication for their risks and benefits. Most importantly, parents should be cautioned that little oversight exists for these compounds and that some have been found to contain unacceptable levels of heavy metals.^[50]Intravenous chelation has been identified by the American Academy of Pediatrics as particularly risky without demonstrated benefit, resulting in 1 reported death.^[37]

Class Summary

Antipsychoticmedications may help with a patient’s aggressive behavior and may improve restricted, repetitive, and stereotyped patterns of behavior and interests.

Risperidone (Risperdal)

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Risperidone is an atypical antipsychotic agent. It binds to the dopamine D2-receptor with 20 times lower affinity than for 5-HT2-receptor affinity. It improves negative symptoms of psychoses and reduces the incidence of extrapyramidal adverse effects compared with conventional antipsychotics. Risperidone is indicated for irritability associated with autistic disorder in children and adolescents aged 6-16 years.

Aripiprazole (Abilify)

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The mechanism of action of aripiprazole is unknown, but it is hypothesized to work differently from other antipsychotics. Aripiprazole is thought to be a partial dopamine (D2) and serotonin (5-HT1A) agonist and to antagonize serotonin (5-HT2A). Additionally, no QTc interval prolongation has been reported in clinical trials.

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Media Gallery

Young child with fragile X syndrome who does not have obvious dysmorphic features. Courtesy of Randi J Hagerman, MD, FAAP.

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Author

Sufen Chiu, MD, PhD Associate Clinical Professor (Volunteer Faculty), University of California, Davis, School of Medicine; Staff Physician, Mercy Medical Group

Sufen Chiu, MD, PhD is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, American Academy of Pediatrics, American Psychiatric Association, California Medical Association, Sierra Sacramento Valley Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Randi J Hagerman, MD, FAAP Professor of Pediatrics, Medical Director of the MIND Institute, Endowed Chair in Fragile X Research, Division of Developmental/Behavioral Pediatrics, University of California Davis Medical Center

Randi J Hagerman, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics, Society for Pediatric Research, Society for Developmental and Behavioral Pediatrics, Western Society for Pediatric Research

Disclosure: Received grant/research funds from Roche for pi on study; Received grant/research funds from Novartis for pi on study; Received grant/research funds from Seaside therapeutics for pi on study; Received grant/research funds from Johnson and Johnson for pi on study; Received grant/research funds from Forest for pi on study; Received grant/research funds from curemark for pi on study.

Sandra M DeJong, MD, MSc Assistant Professor of Psychiatry, Harvard Medical School; Active Staff, Department of Psychiatry, Cambridge Health Alliance

Sandra M DeJong, MD, MSc is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, American Association of Directors of Psychiatric Residency Training, American Psychiatric Association, Association of Women Psychiatrists, Massachusetts Psychiatric Society, New England Council of Child and Adolescent Psychiatry

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

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.