CNS-Active Polypharmacy Affects 10 Percent of Medicare MTM Enrollees in the US

Key Clinical Summary

• In a nationally representative 5% Medicare fee-for-service cohort, 10.7% of Medication Therapy Management (MTM) enrollees in 2021 met criteria for central nervous system (CNS)–active polypharmacy.
• Affected enrollees were more likely to be male, dually enrolled in Medicaid, and have higher comorbidity burden and prior-year health care utilization.
• Only 35% of MTM enrollees with CNS-active polypharmacy completed a comprehensive medication review (CMR), highlighting an opportunity for targeted intervention.

More than 1 in 10 Medicare Part D MTM enrollees experienced CNS-active polypharmacy in 2021, according to a cross-sectional analysis of nationally representative Medicare data. The findings underscore a potentially high-risk subgroup within MTM programs and reveal gaps in participation in comprehensive medication reviews designed to mitigate medication-related harm.

Study Findings

Using 2019-2021 Medicare 5% fee-for-service data linked to 2020-2021 MTM files, investigators evaluated 38 733 community-dwelling beneficiaries aged 66 years and older enrolled in MTM in 2021. CNS-active polypharmacy was defined as at least 30 days of overlapping supply of 3 or more CNS-active medications—including antidepressants, antipsychotics, benzodiazepines, sedative hypnotics, opioids, and antiepileptics—with at least 2 fills per medication in a 7-month lookback period.

Among MTM enrollees, 4144 (10.7%) met criteria for CNS-active polypharmacy. Compared with those without CNS-active polypharmacy, affected enrollees were slightly younger (mean age 72.9 vs 75.0 years) and more likely to be male (71.5% vs 55.0%; standardized mean difference [SMD] = 34.7%) and dually enrolled in Medicaid (42.0% vs 23.9%; SMD = 41.1%). They also had higher comorbidity burden (Charlson Comorbidity Score 6.0 vs 5.0; SMD = 13.2%) and greater prevalence of anxiety, depression, substance use disorder, insomnia, pain, epilepsy, and dementia.

Health care utilization in the prior year was higher among those with CNS-active polypharmacy, including inpatient stays (37.5% vs 29.0%), emergency department visits (53.7% vs 43.0%), outpatient visits (median 7 vs 5), and Medicare costs ($29,157 vs $18,380). They also filled more unique prescription drugs (median 21 vs 15) and more potentially inappropriate medications per Beers Criteria.

Only 35.1% of MTM enrollees with CNS-active polypharmacy completed a CMR, compared with 38.9% of those without. Nearly all CMRs were delivered telephonically. A greater proportion of CMRs in the CNS-active polypharmacy cohort were conducted by community pharmacists (33.1% vs 19.8%), and caregivers were more likely to participate (20% vs 14%). Almost all enrollees received at least 1 targeted medication review (TMR), though the CNS-active polypharmacy cohort received more TMRs overall.

Clinical Implications

CNS-active polypharmacy is associated with impaired cognition and increased fall risk and is monitored as a Medicare Part D quality measure. The 10.7% prevalence among MTM enrollees is nearly double the publicly reported 5.9% rate across all Medicare fee-for-service beneficiaries, suggesting MTM enrollees represent a higher-risk population.

Despite this risk, only about one-third of affected enrollees completed a CMR. Because CMR completion and CNS-active polypharmacy reduction are tied to Medicare quality measures, Part D plan sponsors may have incentives to enhance outreach and engagement, particularly for dually enrolled beneficiaries with greater socioeconomic needs.

The findings suggest that reducing CNS-active polypharmacy may require coordinated deprescribing strategies, prescriber education, and tailored interventions addressing social and financial barriers.

Conclusion

In a nationally representative Medicare MTM cohort, CNS-active polypharmacy affected 10.7% of enrollees and was associated with greater comorbidity and health care use. Limited CMR participation among this high-risk group highlights an opportunity for enhanced engagement and medication safety interventions within Part D MTM programs.

Reference

Hung A, Wilson LE, Smith VA, et al. Characterizing Medicare Medication Therapy Management program enrollees with central nervous system–active polypharmacy. J Manag Care Spec Pharm. 2025; 32(1). doi:10.18553/jmcp.2026.32.1.85