Pharmacologic Treatment of Hyperactivity and Inattentiveness in Autism Spectrum Disorder

Stimulant and Atomoxetine Use in Children with Autism

Autism spectrum disorders (ASDs) and other neurodevelopmental disorders are frequently associated with behavior problems including impulsivity, hyperactivity, disinhibition, and inattentiveness. According to DSM-IV criteria, the presence of an ASD in a child excludes a diagnosis of attention-deficit hyperactivity disorder (ADHD) or attentiondeficit disorder (ADD). Treatment with stimulant medications to target the symptoms characteristic of ADHD/ADD may, however, enhance the adaptive functioning of these children as well as their ability to learn. [Nickels: 2008]
Children with ASDs and symptoms of ADHD/ADD may not respond to treatment with stimulant medication as readily as do other children. In typically developing children with ADHD/ADD, up to 70-80% will show behavioral improvement with methylphenidate or mixed amphetamine salts. In children with ASDs, favorable responses to stimulant medication are seen at rates closer to 45-65%.
Over half of children with ASDs treated with stimulant medication will experience adverse effects. These effects are consistent with the known side effects of stimulant medication in the general population and include sleep disturbance, appetite changes, irritability, anxiety, tics, headache and GI disturbance.
In response to recent concerns regarding the potential cardiotoxic effects of stimulant medications, the American Academy of Pediatrics (AAP) recommends that providers conduct a thorough patient history, family history, and physical exam before starting treatment with stimulant drugs. The AAP does not recommend that children have an electrocardiogram (ECG) unless the patient history, family history, or physical examination raises concerns. Stimulant medications are sympathomimetics with the potential to cause tachycardia and hypertension. For this reason, heart rate and blood pressure should be assessed at baseline and monitored in any individuals taking stimulant medications. [Perrin: 2008]
Guidelines for the initiation and adjustment of stimulant medication in children with ASDs:
  • Begin with a short-acting stimulant such as methylphenidate (MPH).
  • Start with a low dose and increase slowly.
    • Suggested starting dose of MPH for a child: 0.15 mg/kg/dose (or 2.5 mg). For an adolescent, consider beginning with a low dose of a long-acting stimulant in the morning.
    • Titrate upward weekly to a target dose of 0.25-0.5 mg/kg/dose. This is a general guideline. Some children may not show positive effects until higher doses are reached, yet some may experience adverse reactions at the lower doses.
    • Positive effects should be seen immediately or within days of reaching an appropriate dose.
    • Focalin® (the D-isomer of methylphenidate) has approximately twice the potency of Ritalin® when used at equivalent milligram dosing; it is therefore recommended that half the Ritalin®-equivalent dose be used when prescribing Focalin®.
  • Begin with once-daily dosing. If the maximum dose of MPH tolerated by a child is 2.5 mg, may add a second (and third, if needed) daily dose of 2.5 mg. If a child tolerates an MPH dose of 5 mg or more, may convert to a long acting stimulant at 10 mg.
  • Mixed amphetamine salts (Adderall®, Dexedrine®) have not undergone clinical trials in individuals on the autism spectrum. This should not, however, preclude the use of these medications if a clinician feels a trial would be of benefit to a patient.
    • As with MPH, begin at a low dose and slowly adjust upward until positive or adverse effects are seen.
    • At equivalent milligram doses, Dexedrine® has approximately twice the potency of methylphenidate. When using Dexedrine®, begin at half of the methylphenidate-equivalent dose.
    • At equivalent milligram doses, Adderall® is approximately 1.5-fold more potent than methylphenidate. When using Adderall®, use approximately three-fourths of the methylphenidate-equivalent dose.
    • Consider starting with half the initial dose that would be appropriate for a neurotypical child. Begin with once-daily dosing and add a second daily dose as tolerated. Transition to a long-acting formulation when a single dose of 5 mg or higher is tolerated.
    • For an adolescent, consider beginning with a low dose of a long-acting stimulant in the morning.
  • Monitor closely for adverse effects with frequent in-office or phone follow-up.
    • Adverse effects include sleep disturbance, appetite changes, irritability, anxiety, tics, headache and GI disturbance.
    • In children with underlying anxiety, administration of stimulants may worsen anxiety, irritability, and emotional lability. These effects may not occur immediately and may escalate over time. Because of this, parents/teachers may not attribute an increase in anxiety or irritability to the stimulant when they become problematic a month or two out from starting or increasing the stimulant.
    • Mild adverse effects seen initially may be transient and improve over time while taking the medication.
    • If severe adverse effects are experienced, stimulant medication may be discontinued without a taper.
  • Several small trials have been conducted to assess the efficacy and tolerability of atomoxetine in individuals on the autism spectrum with mixed results. [Charnsil: 2010] [Troost: 2006] Atomoxetine may be effective in reducing hyperactivity with less impact on inattentiveness. Favorable effects are typically seen 3-4 weeks after initiating treatment with atomoxetine. As with most other psychotropic medications, individuals on the autism spectrum may be more vulnerable to adverse effects of atomoxetine, which include fatigue, sleep disturbance, irritability, and gastrointestinal disturbance. As with stimulant medications, atomoxetine may cause tachycardia and hypertension. Heart rate and blood pressure should be assessed at baseline and monitored every 6 months. [Arnold: 2006]
    • Begin at 0.5 mg/kg once daily. Increase after one month to 1.2 mg/kg/day in one morning dose or in two evenly divided daily doses.
    • Total daily dose should be no higher than 1.4 mg/kg/day or 100 mg, whichever is lower.
    • In one study of 1357 children prescribed atomoxetine, 6 experienced suicidal events (0.44%).These events tended to occur within 20 days of starting the medication. Clinicans and families should be aware of this low risk of suicidality and have a plan in place regarding the actions that should be taken if it occurs.
  • As with typically developing children, target behaviors in the home and school should be identified at the onset of treatment and monitored for treatment effectiveness. Establish a plan with the family for follow-up. Use objective rating scales such the Nisonger Child Behavior Rating Form (NCBRF) (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

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

Authors & Reviewers

Initial publication: August 2009; last update/revision: August 2010
Current Authors and Reviewers:
Authors: Deborah Bilder, MD
Catherine Jolma, MD

Page Bibliography

Arnold LE, Aman MG, Cook AM, Witwer AN, Hall KL, Thompson S, Ramadan Y.
Atomoxetine for hyperactivity in autism spectrum disorders: placebo-controlled crossover pilot trial.
J Am Acad Child Adolesc Psychiatry. 2006;45(10):1196-205. PubMed abstract

Charnsil C.
Efficacy of Atomoxetine in Children With Severe Autistic Disorders and Symptoms of ADHD: An Open-Label Study.
J Atten Disord. 2010. PubMed abstract

Nickels K, Katusic SK, Colligan RC, Weaver AL, Voigt RG, Barbaresi WJ.
Stimulant medication treatment of target behaviors in children with autism: a population-based study.
J Dev Behav Pediatr. 2008;29(2):75-81. PubMed abstract / Full Text

Perrin JM, Friedman RA, Knilans TK.
Cardiovascular monitoring and stimulant drugs for attention-deficit/hyperactivity disorder.
Pediatrics. 2008;122(2):451-3. PubMed abstract / Full Text

Troost PW, Steenhuis MP, Tuynman-Qua HG, Kalverdijk LJ, Buitelaar JK, Minderaa RB, Hoekstra PJ.
Atomoxetine for attention-deficit/hyperactivity disorder symptoms in children with pervasive developmental disorders: a pilot study.
J Child Adolesc Psychopharmacol. 2006;16(5):611-9. PubMed abstract