Abstract
This pharmacoepidemiology study uses Medicare data to estimate US prescription fills for antidepressants, anxiolytics, antipsychotics, opioids, and antiepileptics among community-dwelling older adults with dementia in 2014-2015, and identifies the most commonly prescribed medications.
A 2015 report highlighted the paucity of knowledge about prescribing of psychotropics to adults with dementia in community settings.1 Prior estimates are more than 10 years old and exclude benzodiazepines and opioids.2,3 Given the risk of harm when prescribing such central nervous system (CNS)–active medications to older adults with dementia, more data are needed to inform research and policy.4 We estimated CNS-active medication prescriptions among community-dwelling older adults with dementia, identifying the most commonly prescribed medications.
Methods
We identified all fee-for-service Medicare beneficiaries aged 65 years or older with a primary or secondary diagnosis of dementia (eTable 1 in the Supplement) on a claim for a face-to-face clinical encounter between October 1, 2014, and September 30, 2015. Analysis was limited to those with Medicare Part D prescription drug coverage and 100 days or fewer in a nursing home during the observation period.
We estimated overall and class-specific CNS-active prescription fills for 5 categories: antidepressants, anxiolytics/sedatives-hypnotics (“anxiolytics”), antipsychotics, opioids, and antiepileptics (eTable 2 in the Supplement).4 Within each class we computed prevalence of prescription fills overall and by demographic strata (Table 1). Log-binomial regression was used to estimate relative prescribing risk, adjusting for demographic characteristics. We identified the top medications prescribed and person-level volume of fills. One fill defined use; a sensitivity analysis was also performed requiring 2 or more fills during the observation period.
Table 1. Prevalence of CNS-Active Medication Prescription Fills Among Community-Dwelling Older Adults With Dementia With Fee-for-Service and Part D Medicare Coverage, Overall and by Demographic Characteristics (N = 737 839).
| Characteristics | Overall, % | Any CNS-active medicationa | Antidepressants | Opioids | Anxiolytics/sedatives-hypnotics | Antiepileptics | Antipsychotics | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| % | ARR (95% CI) | % | ARR (95% CI) | % | ARR (95% CI) | % | ARR (95% CI) | % | ARR (95% CI) | % | ARR (95% CI) | ||
| All | 73.5 | 49.8 | 29.8 | 26.8 | 21.9 | 21.6 | |||||||
| Sex | |||||||||||||
| Female | 66.3 | 75.3 | 1 [Reference] | 52.7 | 1 [Reference] | 30.9 | 1 [Reference] | 28.7 | 1 [Reference] | 21.9 | 1 [Reference] | 22.1 | 1 [Reference] |
| Male | 33.7 | 70.0 | 0.92 (0.92-0.92)b | 44.1 | 0.81 (0.81-0.82)b | 27.7 | 0.88 (0.87-0.89)b | 23.3 | 0.80 (0.79-0.80)b | 22.1 | 0.97 (0.96-0.98)b | 20.7 | 0.94 (0.93-0.94)b |
| Age, y | |||||||||||||
| 65-74 | 19.4 | 80.6 | 1.08 (1.08-1.08)b | 57.8 | 1.15 (1.15-1.16)b | 36.1 | 1.17 (1.16-1.18)b | 33.6 | 1.26 (1.25-1.27)b | 32.3 | 1.41 (1.39-1.42)b | 26.2 | 1.22 (1.20-1.23)b |
| 75-84 | 42.2 | 74.5 | 1 [Reference] | 51.0 | 1 [Reference] | 30.5 | 1 [Reference] | 26.8 | 1 [Reference] | 22.5 | 1 [Reference] | 21.3 | 1 [Reference] |
| ≥85 | 38.4 | 68.7 | 0.91 (0.91-0.92)b | 44.5 | 0.85 (0.84-0.85)b | 25.9 | 0.84 (0.84-0.85)b | 23.5 | 0.86 (0.85-0.86)b | 16.1 | 0.71 (0.71-0.72)b | 19.7 | 0.92 (0.91-0.93)b |
| Race/ethnicityc | |||||||||||||
| Non-Hispanic White | 80.5 | 74.6 | 1 [Reference] | 52.4 | 1 [Reference] | 30.3 | 1 [Reference] | 27.7 | 1 [Reference] | 21.7 | 1 [Reference] | 21.7 | 1 [Reference] |
| Non-Hispanic Black | 9.2 | 66.7 | 0.86 (0.85-0.86)b | 33.6 | 0.61 (0.60-0.62)b | 30.0 | 0.90 (0.89-0.91)b | 18.6 | 0.59 (0.58-0.60)b | 23.0 | 0.89 (0.88-0.91)b | 20.7 | 0.83 (0.82-0.84)b |
| Hispanic | 6.5 | 75.2 | 0.96 (0.95-0.96)b | 47.7 | 0.86 (0.85-0.87)b | 28.8 | 0.85 (0.84-0.86)b | 31.4 | 0.97 (0.96-0.98)b | 24.4 | 0.92 (0.91-0.94)b | 24.1 | 0.93 (0.91-0.95)b |
| Other | 3.8 | 63.1 | 0.82 (0.81-0.83)b | 36.8 | 0.68 (0.67-0.69)b | 22.0 | 0.67 (0.66-0.69)b | 20.2 | 0.65 (0.64-0.67)b | 19.8 | 0.79 (0.77-0.80)b | 17.8 | 0.71 (0.69-0.73)b |
| Low-income subsidy eligibled | |||||||||||||
| No | 70.3 | 72.2 | 1 [Reference] | 50.0 | 1 [Reference] | 28.2 | 1 [Reference] | 25.2 | 1 [Reference] | 19.8 | 1 [Reference] | 19.9 | 1 [Reference] |
| Yes | 29.7 | 76.5 | 1.08 (1.08-1.09)b | 49.4 | 1.05 (1.05-1.06)b | 33.8 | 1.23 (1.22-1.24)b | 30.8 | 1.27 (1.26-1.28)b | 27.0 | 1.36 (1.35-1.37)b | 25.6 | 1.33 (1.31-1.34)b |
| Ruralitye | |||||||||||||
| Urban | 86.6 | 73.3 | 1 [Reference] | 49.8 | 1 [Reference] | 29.1 | 1 [Reference] | 26.7 | 1 [Reference] | 21.8 | 1 [Reference] | 21.9 | 1 [Reference] |
| Rural | 13.4 | 74.5 | 1.00 (0.99-1.00) | 49.7 | 0.96 (0.95-0.97)b | 34.6 | 1.14 (1.13-1.15)b | 28.1 | 1.01 (0.99-1.02) | 22.8 | 0.99 (0.98-1.01) | 20.0 | 0.88 (0.87-0.90)b |
Abbreviations: ARR, adjusted relative risk; CNS, central nervous system.
Medications within each class are as classified by the American Hospital Formulary Service. In a sensitivity analysis requiring 2 or more fills, the prevalences were: any CNS-active medication, 64.4%; antidepressants, 45.0%; opioids, 17.1%; anxiolytics, 19.8%; antiepileptics, 19.0%; and antipsychotics, 18.1%.
P<.001. P value for test examining if use differs from the reference group, adjusting for the other characteristics presented in the table.
Race/ethnicity was identified using the Research Triangle Institute race code variable from the Medicare Master Beneficiary Summary File and was included in the analysis given known racial disparities in CNS-active prescribing.5
The low-income subsidy is a Part D premium assistance program determined by the Social Security Administration based on beneficiary income and assets. For this analysis, the variable was set as “yes” if a beneficiary was eligible for or enrolled in the Part D low-income subsidy for at least 1 month during the observation period.
Rurality was derived using beneficiary zip code and Rural-Urban Commuting Area Codes. Urban areas comprise urban core and suburban areas; rural areas comprise large-town, small-town, and isolated rural areas.
Analyses were conducted using SAS version 9.4 (SAS Institute Inc); tests were 2-sided with α = .05. This study was approved by the Michigan Medicine institutional review board; informed consent was waived.
Results
We identified 737 839 community-dwelling beneficiaries with dementia; the mean age was 82.2 years and 66.3% were female. A total of 73.5% were prescribed any CNS-active medication (Table 1). Prevalence of any prescription fill was highest among beneficiaries who were female (75.3%), aged 65 to 74 years (80.6%), non-Hispanic White (74.6%), and low-income (76.5%). These same groups had the highest adjusted risks. When 2 or more fills were required, the prevalence of any CNS-active medication use was 64.4%.
A total of 49.8% filled an antidepressant prescription and 29.8% an opioid, followed by anxiolytics (26.8%), antiepileptics (21.9%), and antipsychotics (21.6%). Associations between demographics and prescription fills (both prevalent and adjusted risk) were generally consistent in direction for individual drug classes: higher among female, younger (ie, 65-74 years), non-Hispanic White, and low-income older adults. Rurality had mixed associations with prescription fills, with higher prevalence of opioids (34.6% vs 29.1%; difference, 5.5%; 95% CI, 5.2%-5.9%) but slightly lower of antipsychotics (20.0% vs 21.9%; difference, −1.8%; 95% CI, −2.1% to −1.5%).
The opioids hydrocodone (13.5%) and tramadol (12.1%) were the top medications filled (Table 2). Per-person volumes for both were relatively low (medians of 2 prescriptions and 26 days for hydrocodone and 2 prescriptions and 30 days for tramadol). They were followed by a medication from each of the remaining classes: quetiapine (12.0% [antipsychotic]), sertraline (11.3% [antidepressant]), gabapentin (11.2% [antiepileptic]), and lorazepam (9.6% [anxiolytic]).
Table 2. Top 20 CNS-Active Medications Among Community-Dwelling Older Adults With Dementia With Fee-for-Service and Part D Medicare Coverage.
| Rank | Generic name | Medication class | Beneficiaries prescribed medication, % (N = 737 839) | Median (IQR) | |
|---|---|---|---|---|---|
| Fills per person, No. | Supply per person, d | ||||
| 1 | Hydrocodonea | Opioid | 13.5 | 2 (1-5) | 26 (5-120) |
| 2 | Tramadola | Opioid | 12.1 | 2 (1-4) | 30 (12-110) |
| 3 | Quetiapine | Antipsychotic | 12.0 | 6 (2-11) | 240 (90-360) |
| 4 | Sertraline | Antidepressant | 11.3 | 5 (3-11) | 290 (150-360) |
| 5 | Gabapentin | Antiepileptic | 11.2 | 5 (2-9) | 240 (90-359) |
| 6 | Lorazepam | Anxiolytic/sedative-hypnotic | 9.6 | 3 (1-7) | 60 (27-210) |
| 7 | Trazodone | Antidepressant | 9.4 | 4 (2-9) | 180 (61-333) |
| 8 | Mirtazapine | Antidepressant | 9.4 | 5 (2-11) | 240 (90-360) |
| 9 | Citalopram | Antidepressant | 9.1 | 5 (3-11) | 300 (150-360) |
| 10 | Escitalopram | Antidepressant | 8.5 | 5 (3-11) | 283 (143-360) |
| 11 | Alprazolam | Anxiolytic/sedative-hypnotic | 7.7 | 4 (1-8) | 110 (30-270) |
| 12 | Oxycodonea | Opioid | 5.7 | 2 (1-6) | 30 (6-150) |
| 13 | Risperidone | Antipsychotic | 5.5 | 5 (2-11) | 183 (61-350) |
| 14 | Valproate/divalproex | Antiepileptic | 4.3 | 6 (3-11) | 210 (90-360) |
| 15 | Duloxetine | Antidepressant | 4.0 | 6 (3-11) | 300 (140-360) |
| 16 | Clonazepam | Anxiolytic/sedative-hypnotic | 3.9 | 5 (2-10) | 187 (60-330) |
| 17 | Codeinea | Opioid | 3.7 | 1 (1-2) | 10 (4-30) |
| 18 | Levetiracetam | Antiepileptic | 3.3 | 5 (3-11) | 270 (120-360) |
| 19 | Zolpidem | Anxiolytic/sedative-hypnotic | 3.0 | 3 (1-6) | 90 (30-210) |
| 20 | Paroxetine | Antidepressant | 2.9 | 5 (3-11) | 300 (150-360) |
Abbreviations: CNS, central nervous system; IQR, interquartile range.
Includes combination products containing ranked opioids (eg, hydrocodone row includes fills for hydrocodone-acetaminophen).
Discussion
Prescribing of CNS-active medications to community-dwelling Medicare beneficiaries with dementia was frequent, raising concerns about the risk-benefit balance. Opioid prescribing to these patients was common but at relatively low volumes. In contrast, gabapentin and antidepressants were prescribed in larger quantities. There was significant variation in prescription fills by patient demographics.
The analysis reflects prescribing to fee-for-service beneficiaries from 2015 to 2016, which may not generalize to all older adults in 2020. Other limitations include no information available on prescriptions’ appropriateness, and that the data reflect prescription fills as a proxy for use. However, class-specific fills among this cohort with dementia far exceeded that by older adults in the general population in which, for example, antidepressant and antipsychotic use was found among 17.3% and 1.4% of older adults, respectively, in 2013.5 Compared with prior studies of community-dwelling persons with dementia,2,3 the higher overall prevalence of prescription fills is potentially related to the broader scope of CNS-active prescribing captured. Rates found in this study are similar to long-term care settings, in which such prescribing has received significant regulatory attention.6 None of these medications are approved in the US to treat dementia or its behavioral symptoms; all are associated with adverse events among older adults, including falls, sedation, and increased risk of death.4 Work is needed to understand factors driving prescribing given scant evidence of benefit for adults with dementia.
Section Editor: Jody W. Zylke, MD, Deputy Editor.
eTable 1. ICD-9 Codes Used to Identify Medicare Beneficiaries With Dementia
eTable 2. CNS-Active Medications by Class
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eTable 1. ICD-9 Codes Used to Identify Medicare Beneficiaries With Dementia
eTable 2. CNS-Active Medications by Class