Characterizing Medicare Medication Therapy Management program enrollees with central nervous system–active polypharmacy

Abstract

BACKGROUND:

The Medicare Part D Medication Therapy Management (MTM) program uses comprehensive medication reviews (CMRs) and targeted medication reviews to address medication-related problems in older adults. One such problem is central nervous system (CNS)–active polypharmacy, which is associated with impaired cognition and falls in older adults. To date, little is known about the prevalence of CNS-active polypharmacy among MTM enrollees and how they might differ from MTM enrollees without CNS-active polypharmacy; such insights would be helpful to MTM programs developing interventions to reduce CNS-active polypharmacy.

OBJECTIVE:

To (1) estimate the prevalence of MTM enrollees with CNS-active polypharmacy in a nationwide cohort and (2) compare patient characteristics and MTM service use of MTM enrollees with CNS-active polypharmacy vs without.

METHODS:

Cross-sectional, observational study of 2019-2021 Medicare 5% fee-for-service data linked to 2020-2021 MTM data. Patient characteristics and MTM use were compared between MTM enrollees with and without CNS-active polypharmacy.

RESULTS:

Among 38,733 MTM enrollees in 2021, 4,144 (10.7%) experienced CNS-active polypharmacy. Compared with those without CNS-active polypharmacy, the CNS-active polypharmacy cohort was more likely to be male (72% vs 55%, standardized mean difference [SMD] = 34.7%), be dually enrolled in Medicaid (42% vs 24%, SMD = 41.1%), and have greater comorbidity burden (Charlson Comorbidity Score of 6.0 vs 5.0, SMD = 13.2%). The CNS-active polypharmacy cohort also had more prior-year health care utilization, such as being more likely to have an inpatient stay (37.5% vs 29.0%, SMD = 18.1%) or emergency department visit (53.7% vs 43.0%, SMD = 21.6%), as well as number of outpatient visits (7.0 vs 5.0, SMD = 20.8%) and number of unique prescription drugs (21.0 vs 15.0, SMD = 91.9%). The number of targeted medication reviews received was greater in the CNS-active polypharmacy cohort, but a lower proportion (35% vs 39%) participated in a CMR.

CONCLUSIONS:

More than 1 in 10 MTM enrollees experience CNS-active polypharmacy, which is higher than the general Medicare fee-for-service beneficiary population. MTM enrollees with CNS-active polypharmacy are more likely to be male, dually enrolled in Medicaid, and with greater comorbidity burden and prior-year use of health care and medications, suggesting that interventions for this population may need to account for additional clinical and socioeconomic needs. Despite being at greater risk of adverse drug events including impaired cognition and falls, just over one-third of MTM enrollees with CNS-active polypharmacy participate in a CMR, suggesting opportunity for more targeted outreach and intervention by MTM programs, Part D plan sponsors, and Centers for Medicare & Medicaid Services.

Plain language summary

More than 1 in 10 older adults who are enrolled in the Medicare Part D Medication Therapy Management (MTM) program use multiple medications that act on the central nervous system (CNS). This places them at higher risk of falls. Just over one-third of this group participates in a comprehensive medication review that is available to them. We need to improve efforts to engage this group in medication reviews.

Implications for managed care pharmacy

CNS-active polypharmacy is associated with impaired cognition and increased fall risk. We find that more than 10% of MTM enrollees had CNS-active polypharmacy in 2021, and these enrollees are more likely to be male, be dually enrolled in Medicaid, and have greater comorbidity burden and prior-year health care utilization. Only 35% participated in a comprehensive medication review through the MTM program, suggesting a need to improve engagement efforts by MTM programs.

Polypharmacy, commonly defined as the use of at least 5 medications,¹ has increased by more than 3-fold since 1998² and now affects approximately 45% of older adults.³ Although polypharmacy can be appropriate in some cases, it requires routine monitoring because of its association with increased risks of drug-drug interactions, adverse drug events,^4,5 cognitive and functional impairment,⁶ frailty, disability, falls, hospitalizations, and mortality.^7-9 Polypharmacy is also associated with increased chance of inappropriate medication use,^10,11 such as the use of at least 3 medications all acting on the central nervous system (CNS), commonly called CNS-active polypharmacy.¹² The prevalence of CNS-active polypharmacy has grown in older adults¹³ and is independently associated with impaired cognition¹⁴ and increased fall risk.¹² Reduction of CNS-active polypharmacy has become a priority for the Medicare Part D program since 2021, given it is one of only 2 Part D quality measures that currently exist to monitor for medication safety in older adults.¹⁵

To reduce risks of adverse drug events, the Centers for Medicare & Medicaid Services (CMS) requires Part D prescription insurance plan sponsors to provide medication therapy management (MTM) services to their enrollees who meet specific criteria (ie, at least 2-3 chronic conditions, 2-8 medications, and in 2021, at least $4,376 in Part D spending).¹⁶ Two potential opportunities to address CNS-active polypharmacy through the MTM program are through comprehensive medication reviews (CMRs) and targeted medication reviews (TMRs). During a CMR, which are offered at least annually, the MTM provider (most often a pharmacist) reviews the enrollee’s entire list of medications, looks for any drug-related problems (such as interacting medications), creates a medication action plan, discusses with the enrollee, and then reaches out to prescribers with any recommended changes to medication regimens (eg, medication switches or deprescribing). CMRs are mostly provided telephonically, and MTM-eligible enrollees can accept or refuse to participate in CMRs.^17,18 In comparison, TMRs often focus on a specific drug or condition, are conducted at least quarterly, and are not standardized to the same degree as a CMR. For example, real-time direct interaction between patient and MTM provider is not required in a TMR like is required for a CMR. TMRs can include a variety of actions, including any one-way messages sent to patients or prescribers (eg, voice mail, e-mail, fax, secure message to electronic health record system) based on an algorithm detecting an opportunity for improved medication use (eg, too high of a medication dose, inadequate medication adherence).

The MTM program could be helpful for reducing risks of CNS-active polypharmacy at a wide scale, but to the authors’ knowledge, there are no prior studies characterizing CNS-active polypharmacy within the context of the MTM program. To fill this gap, we conducted an exploratory study with several objectives. Our first objective was to estimate the prevalence of CNS-active polypharmacy among MTM enrollees. Our second objective was to compare patient characteristics and MTM service (ie, CMR, TMR) utilization between MTM enrollees with CNS-active polypharmacy and those without. Understanding the prevalence of CNS-active polypharmacy in the MTM enrollee population and their use of MTM services can help CMS and MTM programs better tailor future interventions to reduce CNS-active polypharmacy.

Methods

STUDY DESIGN, DATA, AND SAMPLE

This was a cross-sectional observational study of community-dwelling Medicare fee-for-service beneficiaries in the United States aged 66 years and older who were enrolled in the Part D MTM program in 2021. We used 2019-2021 Medicare fee-for-service data from a random 5% sample that is nationally representative, and we linked these data to 2020-2021 Medicare MTM data. Both datasets were provided by the Centers for Medicare & Medicaid Services. Enrollees with at least 24 months of continuous coverage of Medicare Parts A and B and at least 12 months of continuous coverage of Medicare Part D prior to the MTM enrollment date were included to measure baseline clinical characteristics and prior-year health care utilization. The Strengthening the Reporting of OBservational studies in Epidemiology (STROBE) guideline was followed, and the study was approved by the Duke University Health System institutional review board.

CNS-ACTIVE POLYPHARMACY

MTM enrollees were identified as having CNS-active polypharmacy if they had at least 30 days of overlapping supply of at least 3 CNS-active dispensed medications, including antidepressants, antipsychotics, benzodiazepine and nonbenzodiazepine sedative hypnotics, opioids, and antiepileptics (Supplementary Table 1 ^{(150KB, pdf)} , available in online article). For each of these CNS-active medications, enrollees had to have at least 2 prescription fills on separate dates within the 7 months prior to MTM enrollment to rule out a one-time prescription (Supplementary Figure 1 ^{(150KB, pdf)} ). A 7-month lookback period was applied to ensure we captured 90-day prescription fills, accounting for any lag between the enrollee filling the medications. The exact medications (Supplementary Table 1 ^{(150KB, pdf)} ) were identified based on the Pharmacy Quality Alliance quality measure, Polypharmacy: Use of Multiple CNS-Active Medications in Older Adults,¹⁹ which is based on the American Geriatrics Society Beers Criteria.^12,19 Per the 2021 measure specifications, we excluded skeletal muscle relaxants, which were not added to the quality measure until after they were added to the definition of CNS-active polypharmacy per American Geriatrics Society Beers Criteria in 2023.¹² MTM enrollees not meeting this definition in the 7 months prior to MTM enrollment were labeled as not having CNS-active polypharmacy.

CHARACTERISTICS OF MTM ENROLLEES

Enrollee sociodemographic characteristics identified from Medicare enrollment and claims data included age at MTM enrollment, sex, race, ethnicity, dual enrollment in Medicaid or low-income subsidy without dual enrollment, geographic region, and rural residence.²⁰ Clinical characteristics included the Faurot Frailty Index,²¹ which is a validated algorithm that has been shown to be associated with increased risks of mortality, hospitalization, and skilled nursing facility admission, and the Charlson Comorbidity Score,²² which is a validated algorithm that has been shown to be associated with in-hospital mortality. We also included individual indicators for specific clinical conditions relevant to CNS-active polypharmacy (eg, anxiety, substance use disorder, pain, epilepsy, depression, and dementia) as well as additional chronic diseases that are targeted for MTM eligibility (eg, osteoporosis, diabetes, heart failure, hyperlipidemia, chronic kidney disease, HIV or AIDS, asthmas, and chronic obstructive pulmonary disease).²³ We identified the clinical conditions based on Medicare Chronic Conditions Data Warehouse indicators in the 24 months prior to MTM enrollment,²⁴ except for dementia, which was identified using an algorithm from a prior study.²⁵ Health care utilization measures were measured based on the year before MTM enrollment and included CMR participation, any inpatient stay, any emergency department visit, number of outpatient visits, Medicare costs in 2020-2021 (depending on index date), number of prescription drugs filled, total number of prescription fills, out-of-pocket medication costs in 2020-2021 (depending on index date), number of unique potentially inappropriate medications filled per Beers Criteria,¹² and total number of prescription fills for potentially inappropriate medications.

MTM SERVICES

We identified whether an MTM enrollee participated in a CMR and the number of TMRs that were provided during the 2021 calendar year based on the 2021 MTM data file. Based on available data on the first CMR, we also reported on type of CMR provider (community pharmacist, MTM vendor pharmacist, plan/pharmacy benefit manager pharmacist, other pharmacist including pharmacy intern, or nurse); delivery method (face-to-face vs telephonic); and recipient (patient, caregiver, or other). These detailed data were not reported in the 2021 MTM data file for subsequent CMRs (but as part of preliminary checks on the data, we saw that it was rare for an MTM enrollee to receive more than 1 CMR in the calendar year).

STATISTICAL ANALYSES

Characteristics were summarized using descriptive statistics (count, proportion, mean, SD, median, 25th and 75th percentiles). Enrollee sociodemographic and clinical characteristics, as well as use of MTM services, were compared between the cohort with CNS-active polypharmacy and the cohort without using standardized mean differences (SMDs), with SMDs greater than 10% indicating a significant difference. We relied on SMDs because of the large sample size, but for additional information, also compute and report P values from Mantel-Haenszel χ² tests for categorical variables and Student’s t-test and the Wilcoxon rank-sum test for continuous variables. Analyses were conducted in SAS 9.4 (SAS Institute Inc.).

Results

PREVALENCE OF CNS-ACTIVE POLYPHARMACY AND HOW THESE MTM ENROLLEES DIFFER FROM THOSE WITHOUT CNS-ACTIVE POLYPHARMACY

Out of 38,733 MTM enrollees meeting all study inclusion criteria in 2021, 4,144 (10.7%) had CNS-active polypharmacy and 34,589 (89.3%) did not (Figure 1). Compared with MTM enrollees without CNS-active polypharmacy, the CNS-active polypharmacy cohort was slightly younger (72.9 vs 75.0, SMD = 28.1%) and had greater representation of male (71.5% vs 55.0%, SMD = 34.7%) and White enrollees (87.0% vs 81.9%, SMD = 16.2% for overall race and ethnicity category) (Table 1). The CNS-active polypharmacy cohort was also more likely to be dually enrolled in Medicaid (42.0% vs 23.9%, SMD = 41.1%) and have greater comorbidity burden (Charlson Comorbidity Score of 6.0 vs 5.0, SMD = 13.2%). They were also more likely to have a higher prevalence of conditions related to the CNS-active medications like anxiety (65.6% vs 29.3%, SMD = 78.0%), substance use disorder (17.9% vs 4.8%, SMD = 42.0%), insomnia (46.8% vs 31.8%, SMD = 30.9%), pain (92.0% vs 77.5%, SMD = 41.3%), epilepsy (9.9% vs 2.5%, SMD = 31.3%), depression (71.9% vs 34.1%, SMD = 81.7%), and dementia (17.7% vs 9.4%, SMD = 24.6%; Table 1) and have a higher prevalence of MTM eligibility–related conditions such as osteoporosis (69.5% vs 52.0%, SMD = 36.6%), asthma (20.8% vs 16.0%, SMD = 12.4%), and chronic obstructive pulmonary disease (63.8% vs 51.4%, SMD = 25.2%) (Supplementary Table 2 ^{(150KB, pdf)} ). The CNS-active polypharmacy cohort had more prior-year health care utilization, including being more likely to have an inpatient stay (37.5% vs 29.0%, SMD = 18.1%) or emergency department visit (53.7% vs 43.0%, SMD = 21.6%), as well as number of outpatient visits (7.0 vs 5.0, SMD = 20.8%), cost to Medicare ($29,157.30 vs $18,379.70, SMD = 25.8%), number of unique prescription drugs (21.0 vs 15.0, SMD = 91.9%), number of prescription fills (93.0 vs 53.0, SMD = 87.1%), and number of unique potentially inappropriate medications (1.0 vs 0.0, SMD = 61.5%) and fills (3.0 vs 0.0, SMD = 63.5%) (Supplementary Table 2 ^{(150KB, pdf)} ).

FIGURE 1.

Cohort Flowchart

CNS = central nervous system; MTM = medication therapy management.

TABLE 1.

Characteristics of MTM Enrollees With and Without CNS-Active Polypharmacy

Characteristic	CNS-active polypharmacy (N = 4,144)	No CNS-active polypharmacy (N = 34,589)	SMD (%)	P value
Age at date of MTM enrollment, median (Q1, Q3), years	72.9 (69.0, 78.1)	75.0 (70.7, 80.6)	28.1	<0.001
Sex, n (%)			34.7	<0.001
Female	1,181 (28.5)	15,553 (45.0)
Male	2,963 (71.5)	19,036 (55.0)
Race and ethnicity, n (%)			16.2	<0.001
Unknown	62 (1.5)	853 (2.5)
White	3,607 (87.0)	28,316 (81.9)
Black	260 (6.3)	2,712 (7.8)
Other	42 (1.0)	595 (1.7)
Asian	64 (1.5)	1,074 (3.1)
Hispanic	89 (2.1)	853 (2.5)
North American Native	20 (0.5)	186 (0.5)
Dual enrollment/LIS status, n (%)			41.1	<0.001
None	2,245 (54.2)	25,400 (73.4)
LIS only	159 (3.8)	937 (2.7)
Dual enrolled in Medicaid	1,740 (42.0)	8,252 (23.9)
Geographic region, n (%)			5.3	0.03
Northeast	986 (23.8)	8,163 (23.6)
Midwest	>730	6,823 (19.7)
N/A	—a	25 (0.1)
South	1,584 (38.2)	12,544 (36.3)
West	826 (19.9)	7,034 (20.3)
Rural residence, n (%)	1,186 (28.6)	9,119 (26.4)	5.1	0.002
Charlson Comorbidity Score, median (Q1, Q3)	6.0 (3.0, 8.0)	5.0 (3.0, 8.0)	13.2	<0.001
Clinical conditions
Anxiety	2,717 (65.6)	10,128 (29.3)	78.0	<0.001
Substance use disorder	741 (17.9)	1,674 (4.8)	42.0	<0.001
Insomnia	1,938 (46.8)	11,010 (31.8)	30.9	<0.001
Pain	3,814 (92.0)	26,810 (77.5)	41.3	<0.001
Epilepsy	412 (9.9)	858 (2.5)	31.3	<0.001
Depression	2,979 (71.9)	11,811 (34.1)	81.7	<0.001
Dementia	735 (17.7)	3,243 (9.4)	24.6	<0.001
Faurot Frailty Index, median (Q1, Q3)	0.1 (0.0)	0.1 (0.0)	12.8	<0.001

^a Cell sizes less than 11 cannot be displayed per data use agreement.

CNS = central nervous system; LIS = low-income subsidy; MTM = medication therapy management; Q1 = quartile 1; Q3 = quartile 3; SMD = standardized mean difference.

UTILIZATION OF MTM SERVICES

Of the MTM enrollees with CNS-active polypharmacy, 1,454 (35.1%) participated in a CMR. Of the MTM enrollees without CNS-active polypharmacy, 13,462 (38.9%) participated in a CMR. The distribution of CMR type differed across MTM enrollees with CNS-active polypharmacy vs without (SMD = 35.5%) (Figure 2). In both cohorts, nearly all CMRs (95.3% and 97.2%, respectively) were delivered telephonically, but a greater proportion of CMRs delivered to MTM enrollees with CNS-active polypharmacy were provided by a community pharmacist as compared with those without CNS-active polypharmacy (33.1% vs 19.8%, respectively). Meanwhile, a lower proportion of CMRs delivered to MTM enrollees with CNS-active polypharmacy were provided by an MTM vendor as compared with those without CNS-active polypharmacy (33.6% vs 46.6%, respectively). Additionally, the distribution of CMR participant type differed across MTM enrollees with CNS-active polypharmacy vs without (SMD = 17.8%) (Table 2). Specifically, a higher proportion of caregivers participated in CMRs on behalf of MTM enrollees with CNS-active polypharmacy (20%) than caregivers of MTM enrollees without CNS-active polypharmacy (14%).

FIGURE 2.

CMR Program Variations Among CMR Participants With vs Without CNS-Active Polypharmacy

“Other” includes other pharmacist types, supervised pharmacy interns, and clinical staff (doctors and nursing providers).

CMR = comprehensive medication review; CNS = central nervous system; MTM = medication therapy management; PBM = pharmacy benefit manager; SMD = standardized mean difference.

TABLE 2.

MTM Utilization for MTM Enrollees With and Without CNS-Active Polypharmacy

	CNS-active polypharmacy		No CNS-active polypharmacy		SMD; P value (CNS-active polypharmacy vs no CNS-active polypharmacy)
	CMR participant (N = 1,454)	CMR nonparticipant (N = 2,672)	CMR participant (N = 13,462)	CMR nonparticipant (N = 20,938)
MTM characteristics
Number of TMRs during the calendar year
Mean (SD)	75.0 (72.7)	44.6 (47.0)	66.3 (67.9)	40.7 (47.3)	8.0%; P value <0.001
Median (Q1, Q3)	44.0 (30.0, 82.0)	38.0 (18.0, 44.0)	38.0 (22.0, 62.0)	30.0 (13.0, 44.0)	8.0%; P value <0.001
CMR characteristics
Number of CMRs during the calendar year, mean (SD) [median (Q1, Q3)]	1.0 (0.1) [1.0 (1.0, 1.0)]	n/a	1.0 (0.1) [1.0 (1.0, 1.0)]	n/a	6.4%; P value <0.001
First CMR participant, n (%)					17.8%; P value <0.001
Patient	1,096 (75.4)	n/a	11,116 (82.6)	n/a
Caregiver	284 (19.5)	n/a	1,899 (14.0)	n/a
Othera	74 (5.1)	n/a	457 (3.4)	n/a

Eighteen (0.4%) of those with CNS-polypharmacy and 181 without CNS-polypharmacy (0.5%) are not reported on in the document because they had neither CMR nor TMR.

^a Includes beneficiary’s prescriber and other authorized individuals.

CMR = comprehensive medication review; CNS = central nervous system; MTM = medication therapy management; n/a = not applicable; PBM = pharmacy benefit manager; Q1 = quartile 1; Q3 = quartile 3; SMD = standardized mean difference; TMR = targeted medication review.

Nearly all MTM enrollees received at least 1 TMR (38,526, or 99.5%), and this was similar for both cohorts (99.4% in those with CNS-active polypharmacy and 99.5% in those without CNS-active polypharmacy). However, the CNS-active polypharmacy cohort on average received a greater number of TMRs during the year as compared with the cohort without CNS-active polypharmacy (a median of 44 vs 38 among CMR participants; a median of 38 vs 30 among CMR nonparticipants) (Table 2).

Discussion

In 2021, 10.7% of MTM enrollees had CNS-active polypharmacy that put them at increased risk for adverse drug events, impaired cognition,¹⁴ and falls.¹² This 10.7% rate is lower than a 13.9% rate reported for older adults with dementia,²⁶ but nearly double the average 5.9% that has been publicly reported by CMS across all Medicare for-service beneficiaries nationwide (not limited to MTM enrollees).¹⁵ Although there are differences in how the latter 5.9% is calculated (eg, adjustment for partial enrollment)¹⁵ as compared with the 10.7% determined in this study, we do not expect these differences to account for a near doubling in risk, suggesting that MTM enrollees are at higher risk for CNS-active polypharmacy as compared with the general Medicare fee-for-service beneficiary population. Given that MTM eligibility criteria include having multiple chronic conditions and polypharmacy, it is logical that MTM enrollees would be at higher risk for CNS-active polypharmacy than the general fee-for-service beneficiary population. MTM enrollees are therefore an important target population for Part D plan sponsors to consider in their efforts to reduce concomitant exposure to 3 or more CNS-active medications, which is currently monitored as a Display measure in the Medicare Star Ratings program.¹⁵ This study is the first to report on CNS-active polypharmacy among MTM enrollees with the goal of helping CMS, Part D plan sponsors, and MTM providers better understand and reduce CNS-active polypharmacy.

We find that within the MTM enrollee population, those with CNS-active polypharmacy (vs without) are more likely to be male, dually enrolled in Medicaid, and with greater comorbidity burden including conditions such as anxiety, substance use disorder, insomnia, pain, epilepsy, depression, dementia, osteoporosis, asthma, and chronic obstructive pulmonary disease. Those with CNS-active polypharmacy (vs without) are also more likely to have had prior-year hospitalization and emergency department use as well as increased outpatient visits and costs to Medicare. They also have greater use of prescription drugs, including potentially inappropriate medications in older adults as defined by the Beers criteria.¹² The greater comorbidity burden and prior-year health care and medication utilization suggest that they are a higher-risk population who may need additional support beyond typical interventions to help reduce their CNS-active polypharmacy. Furthermore, MTM enrollees dually enrolled in Medicaid are significantly less likely to participate in CMRs,^27,28 so additional efforts are likely needed to outreach and engage with these individuals. A prior survey of MTM enrollees dually enrolled in Medicaid at a single insurance plan identified not having enough money to pay bills (49%) and lacking support to perform daily activities (47%) as some of their most prevalent needs.²⁹ Deprescribing CNS-active medications may be particularly difficult if they are addressing conditions such as depression, anxiety, or pain and the patient is already lacking support to perform daily activities. As an example, when deprescribing, suggesting pharmacological or nonpharmacological alternatives that do not cost the patient more can help address both needs, and individualized plans are needed to address each patient’s situation.

Our study also finds that only 35% of MTM enrollees with CNS-active polypharmacy participated in a CMR in 2021. This is a dual opportunity for improvement for Part D plan sponsors because higher CMR completion rates are currently incentivized as a Star Rating quality measure and lower CNS-active polypharmacy rates are currently incentivized as a Display quality measure.^30,31 Both Star Rating and Display quality measures can incentivize Part D plan behavior because they can influence enrollment. Furthermore, Star Rating measures are tied to bonus payments, but only for Medicare Advantage Part D plans. CMRs could offer a platform for MTM pharmacists to help reduce CNS-active polypharmacy. Whether CMRs, as currently administered by Part D plans, have an impact on reducing CNS-active polypharmacy is currently unknown. Prior studies have suggested that CMRs can reduce the use of potentially inappropriate medications among MTM enrollees.^32-34 However, effect sizes on average are modest (19% of CMR participants discontinued a potentially inappropriate medication vs 16% of CMR nonparticipants)³² and likely vary by MTM program.^33,34 Outside of Medicare’s MTM program, a 2011 study involving medication reviews focusing on CNS-active medications and performed by community pharmacists found that less than a quarter of pharmacist recommendations were implemented by prescribers, hinting at the need for better coordination of care across the pharmacists and prescribers.³⁵ More recently, a study at an integrated delivery system found that their intervention to reduce CNS-active polypharmacy, which involved deprescribing protocols, physician education, alerts in the electronic health record system, and partnerships involving designated pharmacist/physician champions to answer questions for prescribers, led to a reduction in CNS-active polypharmacy (4.6% in 2018 to 2.8% in 2020) as well as a reduction in the number of users of a single CNS-active medication (6,085 in 2018 to 3,431 in 2020).³⁶ To reduce CNS-active polypharmacy, which often involves patients with difficult needs, CMRs may need to involve greater collaboration, clearer communication and protocols, and prescriber-facing education.

In our study, the number of TMRs received was greater for those with CNS-active polypharmacy (median of 38-44 in those with CNS-active polypharmacy vs 30-38 in those without). Two prior research studies in Medicare MTM enrollees have suggested that TMRs can lead to positive medication changes and help reduce emergency department visits and hospitalizations.^37,38 However, these studies were limited to a single payer or type of MTM program, and nationwide impacts are unknown. Part of the difficulty of a nationwide evaluation of the effectiveness of TMRs is that TMRs encompass a broad swath of interventions, some of which may not relate to the risk of an adverse drug event and instead focus on improving medication adherence. For example, a TMR could involve an automated search using prescription claims data that identifies an inadequate supply of a medication (signaling medication nonadherence), triggering an automatic text or voicemail to the patient or prescriber. Other TMRs could involve an automated search identifying a medication with a dose that is too high with increased risks for older adults, so a fax or e-mail is automatically sent to the prescriber without any communication with the patient. Yet these are the data that are reported to CMS by Part D MTM programs to be able to evaluate TMRs. To assist in future nationwide evaluations of TMRs, CMS should consider requesting that Part D plan sponsors report on different types of TMRs separately so that those addressing medication safety problems like CNS-active polypharmacy can be evaluated.

LIMITATIONS

There are several limitations that must be acknowledged. First, this study included community-dwelling Medicare fee-for-service beneficiaries enrolled in the MTM program in 2021, so results should not be generalized beyond this population, such as to Medicare Advantage beneficiaries. It should also be noted that CMS allows each Part D plan sponsor to set their own MTM eligibility targeting criteria as long as they meet CMS thresholds, so MTM enrollees can vary plan to plan. Second, we did not include skeletal muscle relaxants in our list of CNS-active medications because this drug class was not added to the quality measure until after they were added to the Beers Criteria in 2023,^12,19 so these results may underestimate the prevalence of CNS-active polypharmacy. Third, given that this was a secondary analysis of prescription fill data, it is unknown whether enrollees were actually taking at least 3 CNS-active medications concomitantly. To mitigate against overestimating the prevalence of CNS-active polypharmacy, we aligned with the quality measure’s definition based on not just 1 day of overlapping supply but at least 30 days of overlapping supply of at least 3 CNS-active medications.¹⁹ However, strengths of this study included (1) an in-depth characterization of the MTM enrollees with CNS-active polypharmacy in terms of their sociodemographic, clinical, and health care utilization, as well as use of CMRs and TMRs, and (2) a nationally representative cohort of Medicare fee-for-service MTM enrollees.

Conclusions

We found that more than 1 in 10 MTM enrollees experience CNS-active polypharmacy, which is higher than the general Medicare fee-for-service beneficiary population. MTM enrollees with CNS-active polypharmacy are more likely to be male, dually enrolled in Medicaid, and with greater comorbidity burden and prior-year use of health care and medications, suggesting that interventions for this population may need to account for additional clinical and socioeconomic needs. Despite greater risk, just over one-third of MTM enrollees with CNS-active polypharmacy participate in a CMR, suggesting opportunity for more targeted outreach and intervention by MTM programs, Part D plan sponsors, and CMS.

Disclosures

Dr Hung reports research funding from AstraZeneca and Abbott, consulting for Genentech, and honoraria and conference support from Academy of Managed Care Pharmacy. PQA is the measure steward of the Polypharmacy: Use of Multiple CNS-Active Medications in Older Adults (POLY-CNS) performance measure used in this research. Drs Castora-Binkley and Valdez are employees of PQA. All other authors report no conflicts.

This work was supported by the Health Care Systems Research Network (HCSRN)-Older Americans Independence Centers (OAICs) AGING Initiative (R33AG057806). Investigators were supported by VA HSR&D funding (Career Development Award IK2 HX003359 to Dr Hung, Research Career Scientist RCS 10-391 to Dr Maciejewski), Durham Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT) (CIN 13-410) at the Durham VA Health Care System (Drs Hung, Pavon, Hastings, and Maciejewski), the US Deprescribing Research Network (R24AG064025), and NIA (1R01-AG088214-01 to Dr Pavon, K23AG076889 to Dr Sloan). Dr Sloan is a Health and Aging Policy Fellow and American Political Science Association Fellow and is supported by the John A. Hartford Foundation.

The funders had no role in the design, analysis, or preparation of the paper. The contents do not represent the views of the US Department of Veterans Affairs or the United States Government.