Many taking 10 or more meds

Children with severe neurologic impairment had multiple high-distress symptoms, and their symptom scores were tied to increasing polypharmacy, an analysis of cross-sectional data found.

In a single-center study of 100 children with severe neurologic impairment, parents said their children experienced many concurrent active symptoms, including irritability (65%), insomnia (55%), and pain (54%), reported James Feinstein, MD, MPH, of the University of Colorado School of Medicine, and co-authors in JAMA Network Open.

Children had a median of seven concurrent symptoms, and most children (about 76%) took 10 or more medications. Their median global symptom score (GSS, which ranges from 1 to 100) was 12.1. Per every GSS increase of 10 points, a 12% (95% CI 4%-19%) higher medication count was seen, adjusted for age and number of complex chronic conditions.

“These findings suggest that children with severe neurological impairment reportedly experience substantial symptom burdens and that higher symptom scores are associated with increased medication use,” Feinstein and colleagues wrote. “Paired symptom-medication data may help clinicians identify targets for personalized symptom management, including under-recognized or undertreated symptoms.”

For children who cannot self-report symptoms, no system exists to assess multiple symptoms and their association with medication use, they noted.

“The extremely high symptom burdens reported by parents of children with severe neurological impairment highlights a critical need to better assess and treat symptoms,” wrote Abigail Musial, MD, and Joanna Thomson, MD, MPH, both of Cincinnati Children’s Hospital Medical Center, in an accompanying editorial. “Because the degree of symptom burden was associated with increasing polypharmacy, families and clinicians need to continually and carefully reassess symptoms, therapies, and perceived benefits.”

“Although there is a paucity of evidence to guide the management of many frequently experienced symptoms (e.g., irritability, insomnia, and pain), knowledge of the presence and severity of these symptoms and how they are associated with different medications is a crucial first step to improving symptom management in this population,” they added.

Children with severe neurologic impairment have increased prevalence of chronic health conditions and polypharmacy is common, with associated risk of adverse effects and drug-drug interactions. The Best Pharmaceuticals for Children Act established a framework to review and update priorities for pediatric therapeutics, with emphasis on therapeutics in children with intellectual and developmental disabilities.

In their study, Feinstein and colleagues collected data between April 2019 and December 2019 on participants age 1 to 18 years who were taking five or more medications. Symptoms over the prior 7 days were reported by caregivers on the 28-symptom Memorial Symptom Assessment Scale (MSAS). No patients were able to provide symptom information due to their impairment. MSAS scores were combined to form a global symptom score (GSS).

Children had neurologic diagnoses expected to last a year or more with systemic or multisystem impairment and required pediatric subspecialty care. Severe neurologic impairment includes certain epilepsy syndromes, neurodegenerative disorders, cerebral palsy, hydrocephalus, and other conditions.

Of 100 patients in the study, 55% were male and median age was 9. Nearly two-thirds (62%) had three or more complex chronic conditions.

Outpatient visits were common, with 46% of patients having 20 or more annually, while 50% of patients had two or more inpatient admissions annually. Complex chronic conditions were also common: 4% had none, 25% had 1-2, 35% had 3-4, and 36% had 5 or more conditions. GSS was 9.8 points (95% CI 5.5-14.1 points) higher for those with worse recent health than usual.

Medication counts were 5-9 in 24% of children (median GSS in that group 8.9); 10-14 in 39% (median group GSS 12.5); and 15 or more in 37% (median GSS 16.2).

A majority of patients for whom pain was reported (54% overall) took one or more medication for treatment of pain (61%; 78% if anti-spasticity medications were included), although 39% did not use any analgesic.

“To comprehensively understand pain management in children with severe neurologic impairment, future work should include a diverse population that may experience or report pain differently, evaluation of the multifactorial nature of pain as a symptom, and a more thorough assessment of management (including as-needed medications and integrative therapies,” the editorialists noted.

For those reported to have both constipation (28% overall) and drowsiness (35% overall), use of multiple cholinergic medications was more common than for those not reporting those symptoms. Constipation was treated with one or more medications in 75%, and 61% were taking two or more anticholinergics as treatment. Of those with drowsiness, 63% were treated with 2 or more anticholinergics.

“Highlighting the importance of assessing the medication list to elucidate medications known to provoke symptoms, Feinstein et al found an association between the use of anticholinergic medications and parent-reported constipation and drowsiness, which are known adverse effects of these medications,” the editorialists pointed out.

“The optimization of medications in this population, both through the thoughtful addition of therapies whose benefits outweigh potential adverse effects and deprescribing of medications whose detriments may outweigh their usefulness, has potential to improve symptom burden and quality of life,” they wrote.

Limitations include those of a single-center study. Most children were white, which may limit generalizability. As-needed medications, in addition to other non-pharmacological therapies that are important in pain treatment, were excluded from the study.

  1. Children with severe neurologic impairment had multiple high-distress symptoms, and their symptom scores were tied to increasing polypharmacy in an analysis of cross-sectional data.

  2. Because the degree of symptom burden was associated with increasing polypharmacy, families and clinicians need to continually and carefully reassess symptoms, therapies, and perceived benefits, the editorialists observed.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This project was supported by the NIH National Center for Research Resources Colorado Clinical and Translational Science Institute.

Feinstein was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the NIH.

The editorialists reported no conflicts of interest.

Cat ID: 138

Topic ID: 85,138,130,138,192,925