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Secular Trends in Central Nervous System-Active Polypharmacy Among Serial Cross-Sections of US Adults, 2009–2020

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Abstract

Background

Data comprehensively examining trends in central nervous system (CNS)-active polypharmacy are limited. The objective of this cross-sectional study was to characterize the composition of and trends in CNS-active medication use in US adults.

Methods

We included all participants ≥ 18 years old in the National Health and Nutrition Examination Study (NHANES), 2009–2020. The primary outcome was the percent of adults with CNS-active polypharmacy. This was defined as ≥ 3 medications among antidepressants [tricyclic, selective and serotonin–norepinephrine reuptake inhibitors (SSRIs and SNRIs), opioids, antiepileptics, antipsychotics, benzodiazepines, and nonbenzodiazepine receptor agonists (“Z-drugs”)]. Secondary outcomes included prevalence of any CNS-active medication and specific medications and classes over time, and their indications. Percentages were weighted according to NHANES’s nationally representative sampling frame. log binomial regressions evaluated the relative risk (RR) for each outcome, comparing the last (2017–2020) versus the first (2010–2011) survey cycle.

Results

We included 34,189 adults (18.8% at least 65 years old) from five serial cross-sections (survey cycles). The prevalence of CNS-active polypharmacy was 2.1% in 2009–2010 and 2.6% in 2017–2020 [RR 1.18, 95% confidence interval (CI) 0.94–1.47]. The prevalence of CNS-active polypharmacy did not significantly change within any specific age group (e.g., age at least 65 years: RR 1.29, CI 0.74–2.24). The prevalence of any CNS-active medication was 21.0% in 2009 and 24.6% in 2017–2020 (RR] 1.12, 95% CI 1.02–1.25). A substantial increase occurred for antiepileptics (5.1–8.3%), specifically among participants aged 65 years and older (8.3–13.7%). This was largely driven by increasing gabapentin prevalence (1.4–3.6% overall; 3.3–7.9% age 65 years and older). Anticholinergic, SSRIs/SNRIs, antiepileptics, and benzodiazepines were elevated in most cycles for participants at least 65 years old compared with participants less than 65 years, and opioid use was increased in several cycles for older participants as well. Alprazolam was the most common benzodiazepine and third most common medication for anxiety/depression. Gabapentin was the most common CNS-active medication (3.6% of all participants in 2017–2020), followed by sertraline, citalopram, and acetaminophen-hydrocodone (each ~2%). The most common categories were antidepressants (13.7% in 2017–2020), followed by opioids (5.1% in 2017–2020).

Conclusions

CNS-active medications are increasingly common, particularly gabapentin, and use of any CNS-active medication increased by 12%. Numerous CNS-active classes also increased in older adults throughout the years. Increasing suboptimal medication use highlight the need for further investigation into causes for potentially inappropriate prescribing, particularly for older adults.

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Authors and Affiliations

  1. Department of Neurology, University of Michigan, Taubman 1st Floor, Reception C, 1500 E Medical Center Dr, SPC 5316, Ann Arbor, MI, 48109, USA

    Samuel W. Terman

  2. Division of Geriatric Medicine, Center for Aging and Health, School of Medicine, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA

    Joshua D. Niznik

  3. Division of Pharmaceutical Outcomes and Policy, Eshelman School of Pharmacy, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA

    Joshua D. Niznik

  4. Division of Geriatrics, University of California San Francisco, San Francisco, CA, USA

    Matthew E. Growdon

  5. Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA

    Lauren B. Gerlach

  6. Department of Neurology, The Ohio State University, Columbus, OH, USA

    James F. Burke

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  4. Lauren B. Gerlach
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Correspondence to Samuel W. Terman.

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Funding

Dr. Terman is supported by the American Academy of Neurology Susan S Spencer Clinical Research Training Scholarship and the Michigan Institute for Clinical and Health Research J Award UL1TR002240. Dr. Niznick is supported by the National Institute of Aging K08 AG071794. Dr. Growdon is supported by National Institute of Aging R03AG078804 and Agency for Healthcare Research and Quality K12HS026383. Dr. Gerlach is supported by the National Institute of Aging K23 AG066864. Drs. Terman, Niznick, Growdon, and Gerlach are members of the US Deprescribing Research Network, which is funded by the National Institute on Aging R24AG064025. Dr. Burke reports no relevant funding.

Conflicts of Interest

No authors have any relevant competing or conflicts of interest.

Availability of Data and Material

All datasets are freely available for download at https://wwwn.cdc.gov/nchs/nhanes/Default.aspx.

Ethics Approval

This study was deemed exempt by the University of Michigan Institutional Review Board (HUM00175050), given use of publicly available de-identified datasets.

Consent to Participate

Consenting participants for this study was not required, as we used already-existing publicly available de-identified datasets that were deemed exempt as above.

Consent for Publication

This article does not contain any identifying media or materials that would require patient consent for publication.

Code Availability

Statistical code may be obtained upon request.

Author Contributions

SWT: conceptualization, funding and data acquisition, analysis and methodology, and writing the original manuscript draft. JDN: conceptualization, review, and editing. MEG: conceptualization, review, and editing. LBG: conceptualization, review, and editing. JFB: conceptualization, review, and editing, supervision. We confirm International Committee of Medical Journal Editors authorship criteria for all authors including: (1) substantial contribution to the work, (2) drafting or reviewing the manuscript critically, (3) final manuscript approval, and (4) agreement to be accountable. All authors have read and approved the final submitted manuscript and agree to be accountable for the work.

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Terman, S.W., Niznik, J.D., Growdon, M.E. et al. Secular Trends in Central Nervous System-Active Polypharmacy Among Serial Cross-Sections of US Adults, 2009–2020. Drugs Aging 40, 941–951 (2023). https://doi.org/10.1007/s40266-023-01066-w

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