Polypharmacy Remains Common for Patients With Autism

Heidi Splete

June 24, 2021

Approximately one-third of individuals with autism spectrum disorder (ASD) are prescribed multiple medications to manage comorbidities and symptoms, according to data from a retrospective cohort study of more than 26,000 patients.

"Clinicians caring for patients with ASD are tasked with the challenges of managing the primary disease, as well as co-occurring medical conditions, and coordinating with educational and social service professionals to provide holistic care," wrote Aliya G. Feroe of Harvard Medical School, Boston, and colleagues.

The medication classes used to treat individuals with ASD include ADHD medications, antipsychotics, antidepressants, mood stabilizers, benzodiazepines, anxiolytics, and hypnotics, but the prescription rates of these medications in ASD patients have not been examined in large studies, the researchers said.

In a study published in JAMA Pediatrics, the researchers identified 26,722 individuals with ASD using a United States health care database from Jan. 1, 2014, to Dec. 31, 2019. Data included records of inpatient and outpatient claims, and records of prescriptions filled through commercial pharmacies. Individuals received at least 1 of 24 of the most common medication groups for ASD or comorbidities. The average age of the study participants was 14 years, and 78% were male. Diagnostic codes for ASD were based on the International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.

Over the 6-year study period, approximately one-third of the participants were taking three or more medications at once, ranging from 28.6% to 31.5%. In any 1 year, approximately 41% of children were prescribed a single medication, 17% received two prescriptions, 7.9% received four, and 3.4% received five. Medication changes occurred more frequently within classes than between classes, and reasons for these changes may include patient preference, adverse effects, and cost, the researchers noted.

The overall number of children prescribed particular drugs remained consistent, the researchers noted. "For example, the total number of individuals prescribed methylphenidate shifted from 832 in 2014 to 850 in 2015, 899 in 2016, 863 in 2017, and 838 in 2018," they wrote.

In 15 of the 24 medication groups included in the study, at least 15% of the individuals had unspecified anxiety disorder, anxiety neurosis, or major depressive disorder; in 11 of the medication groups, at least 15% had some form of ADHD. ADHD prevalence in patients taking stimulants varied based on ADHD type, the researchers said.

The most common comorbidities in patients taking antipsychotics were combined type ADHD (11.6%-17.8%) and anxiety disorder (13.1%-30.1%). The study findings suggest that many clinicians are incorporating medications into ASD management, the researchers said.

"Although there is no medical treatment for the core deficits of social communication and repetitive behavioral patterns in ASD, the American Academy of Pediatrics recommends that clinicians consider medications in the management of common comorbid conditions, including seizures, ADHD, anxiety disorders, mood disorders, and disruptive behavior disorders," they said.

The findings were limited by several factors including the potential for inconsistent reporting of diagnoses and pharmacy claims, the researchers noted. Other limitations included a lack of direct clinical assessment to validate diagnoses and the absence of validated diagnostic instruments to screen for comorbidities, they added.

"Our findings suggest that clinicians may be increasingly using integrated approaches to treating patients with ASD and co-occurring conditions, and further work is necessary to determine the relative effects of pharmacotherapy vs. behavioral interventions on outcomes in patients with ASD," the researchers concluded.

Many Reasons for Multiple Medications

"The researchers put in a lot of effort to provide data on a large scale," Herschel Lessin, MD, of Children's Medical Group, Poughkeepsie, N.Y., said in an interview.

"The findings illustrate the reality that autistic children are prescribed a lot of medications for a lot of reasons, some of which are not entirely clear," Lessin said. The study also reflects the chronic lack of behavioral health services for children, he noted. Many children with ASD are referred for services they are unable to access, he said. "As a result, they see doctors who can only prescribe medications to try to control behavior or symptoms for which the cause is unclear," and which could be ASD or other comorbidities, he emphasized.

The large sample size strengthens the study findings, but some of the challenges include the use of claims data, which do not indicate how diagnoses were made, said Lessin. An additional limitation is the fact that many medications for children with autism are used off label, so the specific reason for their use may be unknown, he said.

The take-home message for clinicians is that children with ASD are getting a lot of medications, and pediatricians are not usually responsible for multiple medications," Lessin said. Ultimately, the study is "a plea for more research," to tease out details of what medications are indicated and helpful, he said.

The study received no outside funding. The researchers and Lessin had no financial conflicts to disclose. Lessin serves on the Pediatric News editorial advisory board.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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