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

JAMA Pediatr. 2021 Sep 1;175(9):957-965. doi: 10.1001/jamapediatrics.2021.1329.


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.

MeSH terms

  • Adolescent
  • Amphetamines / administration & dosage
  • Amphetamines / therapeutic use
  • Atomoxetine Hydrochloride / administration & dosage
  • Atomoxetine Hydrochloride / therapeutic use
  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Autism Spectrum Disorder / economics*
  • Autism Spectrum Disorder / epidemiology
  • Bupropion / administration & dosage
  • Bupropion / therapeutic use
  • Child
  • Child, Preschool
  • Cohort Studies
  • Comorbidity*
  • Data Mining / methods
  • Data Mining / statistics & numerical data
  • Depressive Disorder, Major / drug therapy
  • Dexmethylphenidate Hydrochloride / administration & dosage
  • Dexmethylphenidate Hydrochloride / therapeutic use
  • Dextroamphetamine / administration & dosage
  • Dextroamphetamine / therapeutic use
  • Female
  • Health Services Accessibility / statistics & numerical data*
  • Humans
  • Insurance / standards*
  • Insurance / statistics & numerical data
  • Lisdexamfetamine Dimesylate / administration & dosage
  • Lisdexamfetamine Dimesylate / therapeutic use
  • Male
  • Managed Care Programs / organization & administration
  • Managed Care Programs / statistics & numerical data
  • Prevalence
  • Retrospective Studies


  • Amphetamines
  • Bupropion
  • Dexmethylphenidate Hydrochloride
  • Atomoxetine Hydrochloride
  • Lisdexamfetamine Dimesylate
  • Dextroamphetamine