Medication Use in the Management of Comorbidities Among Individuals With Autism Spectrum Disorder From a Large Nationwide Insurance Database | Attention Deficit/Hyperactivity Disorders | JAMA Pediatrics | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Baio  J, Wiggins  L, Christensen  DL,  et al.  Prevalence of autism spectrum disorder among children aged 8 years—Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2014.   MMWR Surveill Summ. 2018;67(6):1-23. doi:10.15585/mmwr.ss6706a1PubMedGoogle Scholar
Madden  JM, Lakoma  MD, Lynch  FL,  et al.  Psychotropic medication use among insured children with autism spectrum disorder.   J Autism Dev Disord. 2017;47(1):144-154. doi:10.1007/s10803-016-2946-7 PubMedGoogle Scholar
Rosen  TE, Mazefsky  CA, Vasa  RA, Lerner  MD.  Co-occurring psychiatric conditions in autism spectrum disorder.   Int Rev Psychiatry. 2018;30(1):40-61. doi:10.1080/09540261.2018.1450229 PubMedGoogle Scholar
Lai  MC, Lombardo  MV, Baron-Cohen  S.  Autism.   Lancet. 2014;383(9920):896-910. doi:10.1016/S0140-6736(13)61539-1 PubMedGoogle Scholar
Maenner  MJ, Shaw  KA, Baio  J,  et al.  Prevalence of autism spectrum disorder among children aged 8 years—Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016.   MMWR Surveill Summ. 2020;69(4):1-12. doi:10.15585/mmwr.ss6904a1 PubMedGoogle Scholar
Leitner  Y.  The co-occurrence of autism and attention deficit hyperactivity disorder in children—what do we know?   Front Hum Neurosci. 2014;8:268. doi:10.3389/fnhum.2014.00268 PubMedGoogle Scholar
Lukmanji  S, Manji  SA, Kadhim  S,  et al.  The co-occurrence of epilepsy and autism: A systematic review.   Epilepsy Behav. 2019;98(Pt A):238-248. doi:10.1016/j.yebeh.2019.07.037PubMedGoogle Scholar
Simonoff  E, Pickles  A, Charman  T, Chandler  S, Loucas  T, Baird  G.  Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample.   J Am Acad Child Adolesc Psychiatry. 2008;47(8):921-929. doi:10.1097/CHI.0b013e318179964f PubMedGoogle Scholar
Kirsch  AC, Huebner  ARS, Mehta  SQ,  et al.  Association of comorbid mood and anxiety disorders with autism spectrum disorder.   JAMA Pediatr. 2019. doi:10.1001/jamapediatrics.2019.4368PubMedGoogle Scholar
Levy  SE, Giarelli  E, Lee  L-C,  et al.  Autism spectrum disorder and co-occurring developmental, psychiatric, and medical conditions among children in multiple populations of the United States.   J Dev Behav Pediatr. 2010;31(4):267-275. doi:10.1097/DBP.0b013e3181d5d03b PubMedGoogle Scholar
Kumar  B, Prakash  A, Sewal  RK, Medhi  B, Modi  M.  Drug therapy in autism: a present and future perspective.   Pharmacol Rep. 2012;64(6):1291-1304. doi:10.1016/S1734-1140(12)70927-1 PubMedGoogle Scholar
McGuire  K, Fung  LK, Hagopian  L,  et al.  Irritability and problem behavior in autism spectrum disorder: a practice pathway for pediatric primary care.   Pediatrics. 2016;137(suppl 2):S136-S148. doi:10.1542/peds.2015-2851L PubMedGoogle Scholar
Volkmar  F, Siegel  M, Woodbury-Smith  M, King  B, McCracken  J, State  M; American Academy of Child and Adolescent Psychiatry (AACAP) Committee on Quality Issues (CQI).  Practice parameter for the assessment and treatment of children and adolescents with autism spectrum disorder.   J Am Acad Child Adolesc Psychiatry. 2014;53(2):237-257. doi:10.1016/j.jaac.2013.10.013 PubMedGoogle Scholar
Bello  NT.  Clinical utility of guanfacine extended release in the treatment of ADHD in children and adolescents.   Patient Prefer Adherence. 2015;9:877-885. doi:10.2147/PPA.S73167 PubMedGoogle Scholar
Lamy  M, Erickson  CA.  Pharmacological management of behavioral disturbances in children and adolescents with autism spectrum disorders.   Curr Probl Pediatr Adolesc Health Care. 2018;48(10):250-264. doi:10.1016/j.cppeds.2018.08.015 PubMedGoogle Scholar
Bartram  LA, Lozano  J, Coury  DL.  Aripiprazole for treating irritability associated with autism spectrum disorders.   Expert Opin Pharmacother. 2019;20(12):1421-1427. doi:10.1080/14656566.2019.1626825 PubMedGoogle Scholar
Williams  K, Brignell  A, Randall  M, Silove  N, Hazell  P.  Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD).   Cochrane Database Syst Rev. 2013;(8):CD004677. doi:10.1002/14651858.CD004677.pub3 PubMedGoogle Scholar
King  BH.  Fluoxetine and repetitive behaviors in children and adolescents with autism spectrum disorder.   JAMA. 2019;322(16):1557-1558. doi:10.1001/jama.2019.11738 PubMedGoogle Scholar
Ne’eman  A, Albrecht  K, Kapp  SK.  Obsessive-compulsive behaviors in autism.   JAMA. 2020;323(8):790. doi:10.1001/jama.2019.21991 PubMedGoogle Scholar
Reddihough  DS, Marraffa  C, Mouti  A,  et al.  Effect of fluoxetine on obsessive-compulsive behaviors in children and adolescents with autism spectrum disorders: a randomized clinical trial.   JAMA. 2019;322(16):1561-1569. doi:10.1001/jama.2019.14685 PubMedGoogle Scholar
Slobbe  LCJ, Füssenich  K, Wong  A,  et al.  Estimating disease prevalence from drug utilization data using the random forest algorithm.   Eur J Public Health. 2019;29(4):615-621. doi:10.1093/eurpub/cky270 PubMedGoogle Scholar
Green  VA, Pituch  KA, Itchon  J, Choi  A, O’Reilly  M, Sigafoos  J.  Internet survey of treatments used by parents of children with autism.   Res Dev Disabil. 2006;27(1):70-84. doi:10.1016/j.ridd.2004.12.002 PubMedGoogle Scholar
Aman  MG, Lam  KSL, Van Bourgondien  ME.  Medication patterns in patients with autism: temporal, regional, and demographic influences.   J Child Adolesc Psychopharmacol. 2005;15(1):116-126. doi:10.1089/cap.2005.15.116 PubMedGoogle Scholar
Martin  A, Sherwin  T, Stubbe  D, Van Hoof  T, Scahill  L, Leslie  D.  Datapoints: use of multiple psychotropic drugs by Medicaid-insured and privately insured children.   Psychiatr Serv. 2002;53(12):1508. doi:10.1176/ PubMedGoogle Scholar
Jobski  K, Höfer  J, Hoffmann  F, Bachmann  C.  Use of psychotropic drugs in patients with autism spectrum disorders: a systematic review.   Acta Psychiatr Scand. 2017;135(1):8-28. doi:10.1111/acps.12644 PubMedGoogle Scholar
Logan  SL, Nicholas  JS, Carpenter  LA, King  LB, Garrett-Mayer  E, Charles  JM.  High prescription drug use and associated costs among Medicaid-eligible children with autism spectrum disorders identified by a population-based surveillance network.   Ann Epidemiol. 2012;22(1):1-8. doi:10.1016/j.annepidem.2011.10.007 PubMedGoogle Scholar
Dalsgaard  S, Nielsen  HS, Simonsen  M.  Five-fold increase in national prevalence rates of attention-deficit/hyperactivity disorder medications for children and adolescents with autism spectrum disorder, attention-deficit/hyperactivity disorder, and other psychiatric disorders: a Danish register-based study.   J Child Adolesc Psychopharmacol. 2013;23(7):432-439. doi:10.1089/cap.2012.0111 PubMedGoogle Scholar
South  M, Costa  AP, McMorris  C.  Death by suicide among people with autism: beyond zebrafish.   JAMA Netw Open. 2021;4(1):e2034018. doi:10.1001/jamanetworkopen.2020.34018 PubMedGoogle Scholar
Benchimol  EI, Smeeth  L, Guttmann  A,  et al; RECORD Working Committee.  The Reporting of Studies Conducted Using Observational Routinely-Collected Health Data (RECORD) statement.   PLoS Med. 2015;12(10):e1001885. doi:10.1371/journal.pmed.1001885 PubMedGoogle Scholar
von Elm  E, Altman  DG, Egger  M, Pocock  SJ, Gøtzsche  PC, Vandenbroucke  JP; STROBE Initiative.  The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.   Bull World Health Organ. 2007;85(11):867-872. doi:10.2471/BLT.07.045120 PubMedGoogle Scholar
Centers for Medicare & Medicaid Services. ICD-9-CM diagnosis and procedure codes: abbreviated and full code titles. October 1, 2014. Accessed April 28, 2020.
Centers for Medicare & Medicaid Services. 2020 ICD-10-CM. September 30, 2019. Accessed April 28, 2020.
Coleman  KJ, Lutsky  MA, Yau  V,  et al.  Validation of autism spectrum disorder diagnoses in large healthcare systems with electronic medical records.   J Autism Dev Disord. 2015;45(7):1989-1996. doi:10.1007/s10803-015-2358-0 PubMedGoogle Scholar
ACT Network. Ontology resources. March 2019. Accessed April 26, 2020.
Visweswaran  S, Becich  MJ, D’Itri  VS,  et al.  Accrual to Clinical Trials (ACT): a clinical and translational science award consortium network.   JAMIA Open. 2018;1(2):147-152. doi:10.1093/jamiaopen/ooy033 PubMedGoogle Scholar
Allaire  JJ, Ellis  P, Gandrud  C,  et al. Package “networkD3.” D3 JavaScript network graphs from R. March 18, 2017. Accessed January 20, 2021.
Rosenberg  RE, Mandell  DS, Farmer  JE, Law  JK, Marvin  AR, Law  PA.  Psychotropic medication use among children with autism spectrum disorders enrolled in a national registry, 2007-2008.   J Autism Dev Disord. 2010;40(3):342-351. doi:10.1007/s10803-009-0878-1 PubMedGoogle Scholar
Supekar  K, Iyer  T, Menon  V.  The influence of sex and age on prevalence rates of comorbid conditions in autism.   Autism Res. 2017;10(5):778-789. doi:10.1002/aur.1741 PubMedGoogle Scholar
Mandell  DS, Morales  KH, Marcus  SC, Stahmer  AC, Doshi  J, Polsky  DE.  Psychotropic medication use among Medicaid-enrolled children with autism spectrum disorders.   Pediatrics. 2008;121(3):e441-e448. doi:10.1542/peds.2007-0984 PubMedGoogle Scholar
Oswald  DP, Sonenklar  NA.  Medication use among children with autism spectrum disorders.   J Child Adolesc Psychopharmacol. 2007;17(3):348-355. doi:10.1089/cap.2006.17303 PubMedGoogle Scholar
Frazier  TW, Shattuck  PT, Narendorf  SC, Cooper  BP, Wagner  M, Spitznagel  EL.  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. 2011;21(6):571-579. doi:10.1089/cap.2011.0057 PubMedGoogle Scholar
Coury  DL, Anagnostou  E, Manning-Courtney  P,  et al.  Use of psychotropic medication in children and adolescents with autism spectrum disorders.   Pediatrics. 2012;130(suppl 2):S69-S76. doi:10.1542/peds.2012-0900D PubMedGoogle Scholar
Gerhard  T, Chavez  B, Olfson  M, Crystal  S.  National patterns in the outpatient pharmacological management of children and adolescents with autism spectrum disorder.   J Clin Psychopharmacol. 2009;29(3):307-310. doi:10.1097/JCP.0b013e3181a20c8a PubMedGoogle Scholar
Hyman  SL, Levy  SE, Myers  SM; Council on Children With Disabilities, Section on Developmental and Behavioral Pediatrics.  Identification, evaluation, and management of children with autism spectrum disorder.   Pediatrics. 2020;145(1):e20193447. doi:10.1542/peds.2019-3447 PubMedGoogle Scholar
Ziskind  D, Bennett  A, Jawad  A, Blum  N.  Therapy and psychotropic medication use in young children with autism spectrum disorder.   Pediatrics. 2020;145(suppl 1):S99-S107. doi:10.1542/peds.2019-1895M PubMedGoogle Scholar
Sandbank  M, Bottema-Beutel  K, Woynaroski  T.  Intervention recommendations for children with autism in light of a changing evidence base.   JAMA Pediatr. 2021;175(4):341-342. doi:10.1001/jamapediatrics.2020.4730 PubMedGoogle Scholar
Spencer  D, Marshall  J, Post  B,  et al.  Psychotropic medication use and polypharmacy in children with autism spectrum disorders.   Pediatrics. 2013;132(5):833-840. doi:10.1542/peds.2012-3774 PubMedGoogle Scholar
Rast  JE, Anderson  KA, Roux  AM, Shattuck  PT.  Medication use in youth with autism and attention-deficit/hyperactivity disorder.   Acad Pediatr. 2021;21(2):272-279. doi:10.1016/j.acap.2020.05.015 PubMedGoogle Scholar
Rubenstein  E, Schieve  L, Wiggins  L,  et al.  Trends in documented co-occurring conditions in children with autism spectrum disorder, 2002-2010.   Res Dev Disabil. 2018;83:168-178. doi:10.1016/j.ridd.2018.08.015 PubMedGoogle Scholar
Koegel  LK, Koegel  RL, Ashbaugh  K, Bradshaw  J.  The importance of early identification and intervention for children with or at risk for autism spectrum disorders.   Int J Speech Lang Pathol. 2014;16(1):50-56. doi:10.3109/17549507.2013.861511 PubMedGoogle Scholar
Rice  CE, Rosanoff  M, Dawson  G,  et al.  Evaluating changes in the prevalence of the autism spectrum disorders (ASDs).   Public Health Rev. 2012;34(2):1-22. doi:10.1007/BF03391685 PubMedGoogle Scholar
Myers  SM, Voigt  RG, Colligan  RC,  et al.  Autism spectrum disorder: incidence and time trends over two decades in a population-based birth cohort.   J Autism Dev Disord. 2019;49(4):1455-1474. doi:10.1007/s10803-018-3834-0 PubMedGoogle Scholar
Mannion  A, Leader  G.  Comorbidity in autism spectrum disorder: a literature review.   Res Autism Spectr Disord. 2013;7(12):1595-1616. doi:10.1016/j.rasd.2013.09.006 Google Scholar
Strom  BL. Overview of electronic databases in pharmacoepidemiology. In: Strom  BL, Kimmel  SE, Hennessy  S, eds.  Pharmacoepidemiology. Wiley; 2019:203-210. doi:10.1002/9781119413431.ch11
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    Views 2,224
    Citations 0
    Original Investigation
    June 7, 2021

    Medication Use in the Management of Comorbidities Among Individuals With Autism Spectrum Disorder From a Large Nationwide Insurance Database

    Author Affiliations
    • 1Harvard Medical School, Boston, Massachusetts
    • 2Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts
    • 3Computational Health Informatics Program, Boston Children’s Hospital, Boston, Massachusetts
    JAMA Pediatr. Published online June 7, 2021. doi:10.1001/jamapediatrics.2021.1329
    Key Points

    Question  How have medications been used recently in the management of symptoms and comorbidities of autism spectrum disorder (ASD)?

    Findings  This population-based cohort study of 26 722 individuals with ASD in the US retrospectively assessed the most common medications used to treat their symptoms and comorbidities during 6 years. Medication type and frequency varied considerably, depending on the comorbidity diagnosed, and individual drug regimens shifted frequently within medication classes over time.

    Meaning  Many individuals with ASD undergo treatment with a wide variety of medications on a trial basis, resulting in frequent changes in drug regimens over time as clinicians attempt to manage associated symptoms and comorbidities.


    Importance  Although there is no pharmacological treatment for autism spectrum disorder (ASD) itself, behavioral and pharmacological therapies have been used to address its symptoms and common comorbidities. A better understanding of the medications used to manage comorbid conditions in this growing population is critical; however, most previous efforts have been limited in size, duration, and lack of broad representation.

    Objective  To use a nationally representative database to uncover trends in the prevalence of co-occurring conditions and medication use in the management of symptoms and comorbidities over time among US individuals with ASD.

    Design, Setting, and Participants  This retrospective, population-based cohort study mined a nationwide, managed health plan claims database containing more than 86 million unique members. Data from January 1, 2014, to December 31, 2019, were used to analyze prescription frequency and diagnoses of comorbidities. A total of 26 722 individuals with ASD who had been prescribed at least 1 of 24 medications most commonly prescribed to treat ASD symptoms or comorbidities during the 6-year study period were included in the analysis.

    Exposures  Diagnosis codes for ASD based on International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.

    Main Outcomes and Measures  Quantitative estimates of prescription frequency for the 24 most commonly prescribed medications among the study cohort and the most common comorbidities associated with each medication in this population.

    Results  Among the 26 722 individuals with ASD included in the analysis (77.7% male; mean [SD] age, 14.45 [9.40] years), polypharmacy was common, ranging from 28.6% to 31.5%. Individuals’ prescription regimens changed frequently within medication classes, rather than between classes. The prescription frequency of a specific medication varied considerably, depending on the coexisting diagnosis of a given comorbidity. Of the 24 medications assessed, 15 were associated with at least a 15% prevalence of a mood disorder, and 11 were associated with at least a 15% prevalence of attention-deficit/hyperactivity disorder. For patients taking antipsychotics, the 2 most common comorbidities were combined type attention-deficit/hyperactivity disorder (11.6%-17.8%) and anxiety disorder (13.1%-30.1%).

    Conclusions and Relevance  This study demonstrated considerable variability and transiency in the use of prescription medications by US clinicians to manage symptoms and comorbidities associated with ASD. These findings support the importance of early and ongoing surveillance of patients with ASD and co-occurring conditions and offer clinicians insight on the targeted therapies most commonly used to manage co-occurring conditions. Future research and policy efforts are critical to assess the extent to which pharmacological management of comorbidities affects quality of life and functioning in patients with ASD while continuing to optimize clinical guidelines, to ensure effective care for this growing population.