Atypical Antipsychotic Medication Use in Children and Adolescents with Autism

Autism spectrum disorders (ASDs) and other neurodevelopmental disorders may be complicated by serious behavior problems such as aggression, irritability, and self-injurious behavior. When faced with a child exhibiting such behaviors, the clinician should take a detailed behavior history and perform a physical exam to determine whether the behaviors are the result of an underlying medical condition or co-occurring psychiatric disorder such as an anxiety disorder. Anxiety often plays a significant role in maladaptive behaviors associated with changes in routine, transitions between activities, separation from a caregiver, or interruption of repetitive or obsessive behaviors.
Recommended first- and second-line pharmacologic treatment for anxiety in individuals on the autism spectrum include selective serotonin reuptake inhibitors (SSRIs) and alpha-2 agonists, respectively. While these medications are not effective in treating the core features of autism (language delay, atypical social development, and restricted interests/stereotypies), they may be helpful when associated anxiety impairs a child’s ability to learn or function. For more information and guidelines regarding the use of these medications, see: Selective Serotonin Reuptake Inhibitors (SSRI) Use in Children with Autism and Other Neurodevelopmental Disabilities, Alpha-2 Agonist Use in Children with Autism.
Atypical antipsychotic medications such as risperidone and aripiprazole are not the first-line medication for any of the maladaptive behaviors seen in children with ASDs. Their use may be warranted in the child with persistent irritability and aggression in whom the use of SSRIs and alpha-2 agonists is ineffective or poorly tolerated. This class of medication may increase appetite and lead to weight gain, insulin resistance, dylipidemia, hyperprolactinemia, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, QTc prolongation, seizures, anticholinergic symptoms, and sedation. Patients may experience akathisia when doses are titrated up or down. Upon discontinuation, these medications should be tapered over months to avoid this adverse effect.[Luby: 2006] [Crawford: 1999] [Williams: 2006]
Rarely, individuals taking these medications may develop extrapyramidal effects (EPS) such as akathisia, dystonia, and potentially irreversible tardive dyskinesia. These effects may occur early or late in the course of treatment, so monitoring for EPS every 6 months is recommended. The Abnormal Involuntary Movement Scale (AIMS) (HHS) (PDF Document 17 KB) is an excellent tool to obtain an objective measure of the presence of EPS. The scale and Abnormal Involuntary Movement Scale (AIMS) Instructions (HHS) (PDF Document 264 KB) may be downloaded free of charge,
Risperidone and aripiprazole are the only atypical antipsychotic medications with US FDA approval to treat symptoms of aggression and irritability in children on the autism spectrum aged 6 years and older. Other medications (such as quetiapine) in this class have been used successfully in this population “off label.” Because limited data is available regarding appropriate dosage, safety, and effectiveness of these medications, consultation with a child psychiatrist is recommended if risperidone or aripiprazole is ineffective or poorly tolerated.
Guidelines for the initiation of risperidone (Risperdal®)
  • Begin with 0.25 mg twice daily.
  • The dose may be increased by 0.25 mg increments after 3 to 4 weeks at each dose.
  • If 1 mg twice daily is not effectively controlling anxiety, consider other medical, environmental, or behavioral problems.
Guidelines for the initiation of aripiprazole (Abilify®)
  • Begin with 1 mg twice daily
  • The dose may be increased by 1 mg increments after 1-2 weeks at each dose.
  • If 5 mg twice daily is not effectively controlling anxiety, consider other medical, environmental, or behavioral problems.
Laboratory studies
Due to the risk of weight gain and associated hyperglycemia and hyperlipidemia, a fasting plasma glucose and lipid panel should be obtained 3 months after initiation of an atypical antipsychotic and every 6 months thereafter. Consider changing to an alternative medication if a child’s weight crosses two percentile lines upward while on an antipsychotic.
Pearls: atypical antipsychotic use in children and adolescents with autism:
  • Medical problems such as chronic sinusitis or abdominal pain may lead to acute behavioral issues that would not respond to behavioral medications.
  • If aggressive behaviors have been reinforced with an outcome that is desired by the patient, of if the aggressive behavior is exhibited as a means to escape an unwanted task, a decrease in the behavior may be seen initially when the patient experiences the sedating effect of an antipsyhcotic medication. In this instance, the negative behavior will generally return as the patient becomes accustomed to the medication. A psychologist or other care provider skilled in behavior modification should be involved in the care of individuals with negative behaviors that are learned.
  • The maximal dose of risperidone (when used by the primary care physician) is 3 mg/day.
  • The maximal dose of aripiprazole (when used by a primary care physician) is 10 mg/day.
  • Note: weight gain can be a significant problem.
  • The Abnormal Involuntary Movement Scale (AIMS) should be administered at follow up visits to monitor for extrapyramidal effects.
Target behaviors in the home and school should be identified at the onset of treatment and monitored to determine treatment effectiveness. Establish a plan with the family for follow-up. Use rating scales such as the Nisonger Child Behavior Rating Form (NCBRF) to get an objective measure of problem behaviors. The NCBRF is a standardized scale for assessing child and adolescent behavior. Scales are available for typically developing children as well as for those with disabilities. They may be downloaded free of charge.
Overdose or misuse of these medications may be life-threatening. Keep this and other medications out of reach from the patient and other children in the household.


Information & Support

For Professionals

Abnormal Involuntary Movement Scale (AIMS) (HHS) (PDF Document 17 KB)
This scale may be used to monitor for extrapyramidal side effects in the individual treated with antipsychotic medications. It is intended for use with the Abnormal Involuntary Movement Scale-Instructions file; from the U.S. Department of Health, Education, and Welfare (HEW), now the U.S. Department of Health and Human Services (HHS).

Abnormal Involuntary Movement Scale (AIMS) Instructions (HHS) (PDF Document 264 KB)
Instructions for use with the Abnormal Involuntary Movement Scale (AIMS); from the U.S. Department of Health, Education, and Welfare (HEW), now the U.S. Department of Health and Human Services (HHS).

Nisonger Child Behavior Rating Form
A standardized tool used in assessing child and adolescent behaviors.

Helpful Articles

Owen R, Sikich L, Marcus RN, Corey-Lisle P, Manos G, McQuade RD, Carson WH, Findling RL.
Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder.
Pediatrics. 2009;124(6):1533-40. PubMed abstract / Full Text

Stigler KA, Diener JT, Kohn AE, Li L, Erickson CA, Posey DJ, McDougle CJ.
Aripiprazole in pervasive developmental disorder not otherwise specified and Asperger's disorder: a 14-week, prospective, open-label study.
J Child Adolesc Psychopharmacol. 2009;19(3):265-74. PubMed abstract / Full Text


Authors: Deborah Bilder, MD - 8/2009
Catherine Jolma, MD - 8/2009
Content Last Updated: 8/2009

Page Bibliography

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Luby J, Mrakotsky C, Stalets MM, Belden A, Heffelfinger A, Williams M, Spitznagel E.
Risperidone in preschool children with autistic spectrum disorders: an investigation of safety and efficacy.
J Child Adolesc Psychopharmacol. 2006;16(5):575-87. PubMed abstract
A randomized placebo-controlled trial showing safety and efficacy for risperidone in preschool children on the autism spectrum.

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