Drug Burden Index in older adults: theoretical and practical issues

Figures & data

Figure 1 Summary of aspects of the DBI.

Notes: +, positive association; +/−, inconsistent association.
Abbreviations: RCT, randomized controlled trial; GP, general practitioner.

Table 1 Example of mathematical calculation of the Drug Burden Index (using clinical scenario)

Medications in clinical scenario	Daily dose (D)	Minimum recommended daily dose (δ)	Individual DBI
Irbesartan 300 mg, daily	300 mg	75 mg (no anticholinergic or sedative effects)	0
Darifenacin 15 mg, daily	15 mg	7.5 mg (anticholinergic effects)	0.67
Temazepam 7.5 mg, at night	7.5 mg	7.5 mg (sedative effects)	0.50
Acetaminophen 300 mg, 2 tablets tds	1,800 mg	300 mg (no anticholinergic or sedative effects)	0
Codeine 15 mg, 2 tablets tds	90 mg	120 mg (sedative effects)	0.43
Total DBI calculation
$DBI={\displaystyle \sum \frac{D}{D+\delta }}$			1.60

Notes: This is an example of a medication regimen for an older adult in the USA; minimum daily dose as recommended by the US Food and Drug Administration.

Abbreviations: tds, three times a day; DBI, Drug Burden Index.

Table 2 Evidence supporting the association of the Drug Burden Index with outcomes: cross-sectional and longitudinal studies categorized by participant setting

Study setting, population age	Country (n)	Prevalence % DBI >0 or mean (± SD) DBI score	DBI association with outcomes	Resource used to identify minimum effective dose (δ) of medications
Cross-sectional, community-dwelling older adults
70–79 years	USA (3,075)	0.18±0.35	DBI was associated with poorer physical function and cognition^Citation12	FDA
≥70 years^Citation91,*	Australia (1,705)	0.18±0.35	Higher DBI was associated with poorer physical performance and functional status^Citation24	TGA
≥70 years^Citation91,*	Australia (1,662)	Robust 20.1% Pre frail 29.7% Frail 45.5%	Higher DBI may contribute to frailty^Citation27	TGA
≥70 years^Citation91,*	Australia (987)	27.8%	DBI was not associated with limitations on objective cognitive measures or with cognitive impairment^Citation32	TGA
≥75 years	Finland (700)	36.7%	DBI was associated with functional impairment^Citation25	Pharmaca Fennica
≥75 years	Finland (339)	37.5%	Exposure to DBI medications was associated with a greater use of hospital days^Citation83	Pharmaca Fennica
Admitted to geriatric medicine units, >60 years	UK (362)	Median (IQR) 0.48 (0.00–1.00)	Higher DBI scores on admission were independently associated with length of hospital stay and lower scores in functional measures^Citation84	BNF
Cross-sectional, residential aged care or hospitalized older adults
≥70 years	Australia (602)	69.9%	DBI was only associated with impairment in balance and not with physical function^Citation26 DBI was significantly and independently associated with falls in older people^Citation29 High exposure to DBI medications showed no significant association between increased DBI and mortality^Citation30	TGA sourced from MIMS^Citation85
≥70 years	Australia (115)	0.24±0.40	DBI was associated with impairments in physical functioning^Citation23	TGA
≥65 years	The Netherlands (71)	Median (range) for ACh component 0.00 (0.00–1.75)	ACh-DBI was significantly associated with 3-month and one-year mortality^Citation18	BNF
≥65 years	Australia (226)	78.8%	A DBI >0 was associated with poorer self-reported quality of life outcomes^Citation86	N/A
≥65 years^Citation50,**	USA (112)	N/A	High DBI scores were associated with poor clinical outcomes and longer lengths of hospital stay^Citation50	Physicians’ Desk Reference^Citation22 and product information for individual drugs
Longitudinal, community-dwelling
70–79 years	USA (2,172)	34% At 5 years, 29%	Increased exposure to high DBI medications was associated independently with lower physical function over 5 years^Citation87	FDA
Outpatient clinics, ≥60 years (ACh component of DBI used)	Canada (102)	0.1±0.2 At one year, 0.6±0.2	An increase in the ACh-DBI correlated with poorer delayed memory performance^Citation88	CPS
Data extracted from pharmaceutical claims data of older people, ≥65 years	New Zealand (533,129)	31.8%	Anticholinergic exposure as measured by the ACh-DBI was prominent in the population, even amongst users of acetylcholinesterase inhibitors^Citation89	Medsafe
Data extracted from pharmaceutical claims data of older people, ≥65 years	New Zealand (537,387)	43.2%	Polypharmacy (≥5 medications) was highly associated with DBI exposure. DBI exposure was associated with falls-related hospitalization and greater numbers of GP visits. DBI >0 was associated with higher mortality risk^Citation90	Medsafe
Linked data extracted from prescription, special reimbursement, and hospital discharge registers, ≥65 years	Finland (16,603) with AD (16,603) without AD	51.4% 33.3%	A dose-response relationship existed between DBI medications and hospitalization and mortality in people with and without AD^Citation31	Pharmaca Fennica

Notes:

* Study conducted as part of Concord Health and Aging in Men Project

** this study used a modified DBI calculation for investigating study aims.

Abbreviations: FDA, Food and Drug Administration; TGA, Therapeutic Goods Administration of Australia; GP, general practitioner; MIMS, Monthly Index of Medical Specialties; ACh, anticholinergic; DBI, Drug Burden Index; N/A, not available; AD, Alzheimer’s disease; BNF, British National Formulary of the British Medical Association and the Royal Pharmaceutical Society; Pharmaca Fennica, source of Finnish registered medication product information; CPS, Compendium of Pharmaceuticals and Specialities from the Canadian Pharmacists Association; Medsafe, source of New Zealand product safety data sheets; IQR, interquartile range; SD, standard deviation.

Table 3 Studies of the Drug Burden Index in clinical practice

Study setting, population age	Country (n)	Intervention or audit	DBI score at baseline and post-intervention or audit	DBI association with outcomes	Resource used to identify minimum effective dose (δ) of medications
Residential aged care home patients, ≥65 years	Australia (500)	RMMR^Citation33	Median (IQR) Pre 0.50 (0–1.0) Post 0.33 (0–0.67)	RMMR intervention resulted in a statistically significant decrease in median DBI score^Citation35	FDA
Community-dwelling older people, ≥65 years	Australia (372)	HMR^Citation33	Median (IQR) Pre 0.50 (0–0.89) Post 0.22 (0–0.66)	Statistically significant decrease in the total DBI scores for all patients receiving an HMR service^Citation34	FDA
Self-care retirement village older adults, ≥70 years	Australia (115)	Intervention targeting GP prescribing practices	Prevalence % DBI >0, pre, post; Intervention group 33%, 32% Control group 53%, 19%	Intervention did not achieve anticipated outcomes. DBI decreased in both control and intervention groups^Citation37	TGA
Hospitalized patients, ≥65 years	Australia (329)	Retrospective audit of medical records	Mean (95% CI) On admission 0.41 (0.34–0.47) On discharge 0.36 (0.30–0.41)	DBI was associated with an increased risk of hospital admission for delirium^Citation92	TGA sourced from the MIMS^Citation85
Hospitalized patients, ≥65 years	USA (229)	Retrospective audit of medical records	Mean ± SD On admission 1.00±0.92 On readmission 1.55±1.26	DBI scores were higher in patients readmitted to hospital^Citation93	FDA

Abbreviations: DBI, Drug Burden Index; IQR, interquartile range; CI, confidence interval; SD, standard deviation; FDA, US Food and Drug Administration; TGA, Therapeutic Goods Administration of Australia; MIMS, Monthly Index of Medical Specialties; RMMR, Residential Medication Management Review; HMR, Home Medicine Review; GP, general practitioner.

Table 4 Comparison of developing and calculating anticholinergic scales (by publication year) with the Drug Burden Index*

	DBI^Citation12 (2007)	ADS^Citation58 (2006)	ABC^Citation59 (2006)**	CrAS^Citation60 (2008)	ARS^Citation61 (2008)	ACB^Citation64 (2008)	AAS^Citation62 (2010)***	ACL^Citation63 (2011)****
Basis of scale concept
Pharmacological first principles	✓				✓
Serum radioreceptor assays or SAA		✓	✓		✓	✓	✓	✓
Extensive literature reviews (including systematic reviews)			✓		✓	✓
Interdisciplinary clinician rating scales or expert opinion			✓	✓	✓	✓	✓	✓
Scoring system or calculation equations used
Categoric or numeric scale used		✓	✓	✓	✓	✓	✓	✓
Pharmacological equation used	✓
Summation or accumulation of effect	✓	✓	✓	✓	✓	✓	✓
Dose consideration	✓	✓
Medication identification resource
Country-specific product information/label or package insert	✓	✓
Others (eg, literature appraisals)				✓	✓	✓	✓	✓
Number of anticholinergic medications considered	Variable^ 128	117	27	60	49	88	99	49

^ Notes: Number of medications included in the DBI calculation includes sedative and anticholinergic medications and varies according to each country’s formulary at the time of the study; the number reported here is the number of anticholinergic and sedative medications that a cohort of 2,172 older adults in the USA was exposed to;⁸⁷

* human studies only

** based on previous work by Han et al⁹⁴

*** calculation based on Chew et al⁹⁵

**** calculation based on Chew et al⁹⁵ and Ancelin et al.⁵⁹

Abbreviations: SAA, serum anticholinergic activity; ADS, Anticholinergic Drug Scale; ABC, Anticholinergic Burden Classification; CrAS, Clinician-rated Anticholinergic Score; ARS, Anticholinergic Risk Scale; AAS, Anticholinergic Activity Scale; ACL, Anticholinergic Loading Scale; ACB, Anticholinergic Cognitive Burden Scale; DBI, Drug Burden Index.

Table 5 Comparison of developing sedative scales (by publication year) with the Drug Burden Index*

	DBI (2007)^Citation12	Sedative load (2003)^Citation65,Citation66	Sloane et al (2008)^Citation67,**	CNS drug (2009)^Citation68^–^Citation70
Basis of scale concept
Pharmacological first principles	✓		✓	✓
Extensive literature reviews (including systematic reviews)		✓
Interdisciplinary clinician rating scales or expert opinion		✓	✓
Scoring system or calculation equations used
Categoric or numeric scales used		✓	✓	✓
Pharmacological equation used	✓	✓	✓	✓
Summation or accumulation of effect	✓	✓	✓	✓
Dose consideration	✓		✓	✓
Medication identification resource
Anatomical Therapeutic Classification System		✓	✓
Iowa Drug Information System Codes				✓
Country-specific product information/label or package insert	✓	✓	✓
Number of sedative medications considered	Variable^ 128^Citation87	340^Citation65	106	53^Citation70

Notes:

^ Number of medications included in the DBI calculation includes sedative and anticholinergic medications and varies according to each country’s formulary at the time of the study; the number reported here is the number of anticholinergic and sedative medications that a cohort of 2,172 older adults in the USA was exposed to

* human studies only

** based on calculations from sedative load.

Abbreviations: DBI, Drug Burden Index; CNS, central nervous system.

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