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First published online December 21, 2020

Pharmacotherapy of attention deficit/hyperactivity disorder in individuals with autism spectrum disorder: A systematic review of the literature

Abstract

Aim:

To assess the empirical evidence for the treatment of attention deficit/hyperactivity disorder (ADHD) in populations with autism spectrum disorder (ASD).

Methods:

A systemic PubMed, PsychINFO, Embase, and Medline database search of peer-reviewed literature was conducted. Included in the review were controlled trials published in English with sample sizes ⩾10 participants examining the safety and efficacy of anti-ADHD medication in ASD populations. Data was extracted on relevant variables of study design, demographics, associated psychopathology, medication dose, efficacy, and tolerability.

Results:

Nine controlled trials met the inclusion and exclusion criteria: five with methylphenidate, three with atomoxetine, and one with guanfacine. Sample sizes ranged from 10 to 128 with 430 children participating across all the trials. In all the trials, treatment response was significantly superior to placebo. However, almost all trials assessed only hyperactivity, and most included only participants with intellectual disability with high levels of irritability. None of the trials distinguished agitation from hyperactivity. The response on hyperactivity for methylphenidate and atomoxetine was less than that observed in the neurotypical population; however, the response for guanfacine surpassed results observed in neurotypical populations. Treatment-emergent mood lability (i.e. mood dysregulation and mood-related adverse events) was frequently associated with methylphenidate and guanfacine treatments. Worse treatment outcomes were associated with individuals with lower intellectual capability compared with those with higher IQs.

Conclusions:

here is a scarcity of controlled trials examining ADHD treatments in ASD populations, particularly in intellectually capable individuals with ASD and in adults. Response to ADHD medications in ASD were adversely moderated by the presence of intellectual disability and mood lability.

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References

American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington: American Psychiatric Association.
Arnold LE, Aman MG, Cook AM, et al. (2006) Atomoxetine for hyperactivity in autism spectrum disorders: Placebo-controlled crossover pilot trial. J Am Acad Child Adolesc Psychiatry 45: 1196–1205.
Biederman J, Melmed RD, Patel A, et al. (2008) A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics 121: e73–e84.
Centers for Disease Control and Prevention (2018) Autism Prevalence Slightly Higher in CDC’s ADDM Network. Available at: https://www.cdc.gov/media/releases/2018/p0426-autism-prevalence.html.
de Bruin EI, Ferdinand RF, Meester S, et al. (2007) High rates of psychiatric co-morbidity in PDD-NOS. J Autism Dev Disord 37: 877–886.
Fankhauser MP, Karumanchi VC, German ML, et al. (1992) A double-blind, placebo-controlled study of the efficacy of transdermal clonidine in autism. J Clin Psychiatry 53: 77–82.
Frazier TW, Shattuck PT, Narendorf SC, et al. (2011) Prevalence and correlates of psychotropic medication use in adolescents with an autism spectrum disorder with and without caregiver-reported attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 21: 571–579.
Ghuman JK, Aman MG, Lecavalier L, et al. (2009) Randomized, placebo-controlled, crossover study of methylphenidate for attention-deficit/hyperactivity disorder symptoms in preschoolers with developmental disorders. J Child Adolesc Psychopharmacol 19: 329–339.
Gjevik E, Eldevik S, Fjaeran-Granum T, et al. (2011) Kiddie-SADS reveals high rates of DSM-IV disorders in children and adolescents with autism spectrum disorders. J Autism Dev Disord 41: 761–769.
Handen BL, Aman MG, Arnold LE, et al. (2015) Atomoxetine, parent training, and their combination in children with autism spectrum disorder and attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 54: 905–915.
Handen BL, Johnson CR, Lubetsky M (2000) Efficacy of methylphenidate among children with autism and symptoms of attention-deficit hyperactivity disorder. J Autism Dev Disord 30: 245–255.
Handen BL, Sahl R, Hardan AY (2008) Guanfacine in children with autism and/or intellectual disabilities. J Dev Behav Pediatr 29: 303–308.
Harfterkamp M, van de Loo-Neus G, Minderaa RB, et al. (2012) A randomized double-blind study of atomoxetine versus placebo for attention-deficit/hyperactivity disorder symptoms in children with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry 51: 733–741.
Jaselskis CA, Cook EH Jr, Fletcher KE, et al. (1992) Clonidine treatment of hyperactive and impulsive children with autistic disorder. J Clin Psychopharmacol 12: 322–327.
Joshi G, DiSalvo M, Faraone SV, et al. (2020a) Predictive utility of autistic traits in youth with ADHD: A controlled 10-year longitudinal follow-up study. Eur Child Adolesc Psychiatry 29: 791–801.
Joshi G, DiSalvo M, Wozniak J, et al. (2020b) A prospective open-label trial of long-acting liquid methylphenidate for the treatment of attention deficit/hyperactivity disorder in intellectually capable adults with autism spectrum disorder. World J Biol Psychiatry 21: 274–290.
Joshi G, Petty C, Wozniak J, et al. (2010) The heavy burden of psychiatric comorbidity in youth with autism spectrum disorders: A large comparative study of a psychiatrically referred population. J Autism Dev Disord 40: 1361–1370.
Joshi G, Wozniak J, Petty C, et al. (2013) Psychiatric comorbidity and functioning in a clinically referred population of adults with autism spectrum disorders: A comparative study. J Autism Dev Disord 43: 1314–1325.
Levy SE, Giarelli E, Lee LC, et al. (2010) Autism spectrum disorder and co-occurring developmental, psychiatric, and medical conditions among children in multiple populations of the United States. J Dev Behav Pediatr 31: 267–275.
Leyfer OT, Folstein SE, Bacalman S, et al. (2006) Comorbid psychiatric disorders in children with autism: Interview development and rates of disorders. J Autism Dev Disord 36: 849–861.
Mattila ML, Hurtig T, Haapsamo H, et al. (2010) Comorbid psychiatric disorders associated with Asperger syndrome/high-functioning autism: A community- and clinic-based study. J Autism Dev Disord 40: 1080–1093.
Michelson D, Allen AJ, Busner J, et al. (2002) Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: A randomized, placebo-controlled study. Am J Psychiatry 159: 1896–1901.
Pearson DA, Santos CW, Aman MG, et al. (2013) Effects of extended release methylphenidate treatment on ratings of attention-deficit/hyperactivity disorder (ADHD) and associated behavior in children with autism spectrum disorders and ADHD symptoms. J Child Adolesc Psychopharmacol 23: 337–351.
Quintana H, Birmaher B, Stedge D, et al. (1995) Use of methylphenidate in the treatment of children with autistic disorder. J Autism Dev Disord 25: 283–294.
Research Units on Pediatric Psychopharmacology Autism Network (2005) Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Arch Gen Psychiatry 62: 1266–1274.
Ruggiero S, Clavenna A, Reale L, et al. (2014) Guanfacine for attention deficit and hyperactivity disorder in pediatrics: A systematic review and meta-analysis. Eur Neuropsychopharmacol 24: 1578–1590.
Scahill L, McCracken JT, King BH, et al. (2015) Extended-release guanfacine for hyperactivity in children with autism spectrum disorder. Am J Psychiatry 172: 1197–1206.
Schwartz S, Correll CU (2014) Efficacy and safety of atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder: Results from a comprehensive meta-analysis and metaregression. J Am Acad Child Adolesc Psychiatry 53: 174–187.
Sinzig J, Walter D, Doepfner M (2009) Attention deficit/hyperactivity disorder in children and adolescents with autism spectrum disorder: Symptom or syndrome? J Atten Disord 13: 117–126.
Stahlberg O, Soderstrom H, Rastam M, et al. (2004) Bipolar disorder, schizophrenia, and other psychotic disorders in adults with childhood onset AD/HD and/or autism spectrum disorders. J Neural Transm (Vienna) 111: 891–902.
Wilens T, McBurnett K, Stein M, et al. (2005) ADHD treatment with once-daily OROS methylphenidate: Final results from a long-term open-label study. J Am Acad Child Adolesc Psychiatry 44: 1015–1023.
Wozniak J, Biederman J, Faraone SV, et al. (1997) Mania in children with pervasive developmental disorder revisited. J Am Acad Child Adolesc Psychiatry 36: 1552–1559; discussion 1559–1560.

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Published In

Article first published online: December 21, 2020
Issue published: March 2021

Keywords

  1. ADHD
  2. ASD
  3. treatment

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© The Author(s) 2020.
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PubMed: 33349107

Authors

Affiliations

Gagan Joshi
Alan and Lorraine Bressler Clinical and Research Program for Autism Spectrum Disorder, Massachusetts General Hospital, Boston, USA
Clinical and Research Program in Pediatric Psychopharmacology, Massachusetts General Hospital, Boston, USA
Department of Psychiatry, Harvard Medical School, Boston, USA
Timothy Wilens
Alan and Lorraine Bressler Clinical and Research Program for Autism Spectrum Disorder, Massachusetts General Hospital, Boston, USA
Clinical and Research Program in Pediatric Psychopharmacology, Massachusetts General Hospital, Boston, USA
Department of Psychiatry, Harvard Medical School, Boston, USA
Elizabeth S Firmin
Alan and Lorraine Bressler Clinical and Research Program for Autism Spectrum Disorder, Massachusetts General Hospital, Boston, USA
Clinical and Research Program in Pediatric Psychopharmacology, Massachusetts General Hospital, Boston, USA
Barbora Hoskova
Alan and Lorraine Bressler Clinical and Research Program for Autism Spectrum Disorder, Massachusetts General Hospital, Boston, USA
Clinical and Research Program in Pediatric Psychopharmacology, Massachusetts General Hospital, Boston, USA
Joseph Biederman
Alan and Lorraine Bressler Clinical and Research Program for Autism Spectrum Disorder, Massachusetts General Hospital, Boston, USA
Clinical and Research Program in Pediatric Psychopharmacology, Massachusetts General Hospital, Boston, USA
Department of Psychiatry, Harvard Medical School, Boston, USA

Notes

Gagan Joshi, Alan and Lorraine Bressler Clinical and Research Program for Autism Spectrum Disorder, Massachusetts General Hospital, 55 Fruit Street, WRN 626, Boston, MA 02114, USA. Email: [email protected]

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