Abstract
Background
Anticholinergic drugs are often involved in explicit criteria for inappropriate prescribing in older adults. Several scales were developed for screening of anticholinergic drugs and estimation of the anticholinergic burden. However, variation exists in scale development, in the selection of anticholinergic drugs, and the evaluation of their anticholinergic load. This study aims to systematically review existing anticholinergic risk scales, and to develop a uniform list of anticholinergic drugs differentiating for anticholinergic potency.
Methods
We performed a systematic search in MEDLINE. Studies were included if provided (1) a finite list of anticholinergic drugs; (2) a grading score of anticholinergic potency and, (3) a validation in a clinical or experimental setting. We listed anticholinergic drugs for which there was agreement in the different scales. In case of discrepancies between scores we used a reputed reference source (Martindale: The Complete Drug Reference®) to take a final decision about the anticholinergic activity of the drug.
Results
We included seven risk scales, and evaluated 225 different drugs. Hundred drugs were listed as having clinically relevant anticholinergic properties (47 high potency and 53 low potency), to be included in screening software for anticholinergic burden.
Conclusion
Considerable variation exists among anticholinergic risk scales, in terms of selection of specific drugs, as well as of grading of anticholinergic potency. Our selection of 100 drugs with clinically relevant anticholinergic properties needs to be supplemented with validated information on dosing and route of administration for a full estimation of the anticholinergic burden in poly-medicated older adults.
Similar content being viewed by others
References
Tune LE (2001) Anticholinergic effects of medication in elderly patients. J Clin Psychiatry 62(suppl 21):11–14
Hilmer SN, McLachlan A, Le Couteur DG (2007) Clinical pharmacology in the geriatric patient. Fundam Clin Pharmacol 21:217–320
de Leon J (2011) Paying attention to pharmacokinetic and pharmacodynamic mechanisms to progress in the area of anticholinergic use in geriatric patients. Curr Drug Metab 12(7):635–646
Shi S, Klotz U (2011) Age-related changes in pharmacokinetics. Curr Drug Metab 12(7):601–610
Remillard AJ (1996) A pharmacoepidemiological evaluation of anticholinergic prescribing patterns in the elderly. Pharmacoepidemiol Drug Saf 5:155–164
Ness J, Hoth A, Barnett MJ, Shorr RI, Kaboli PJ (2006) Anticholinergic medications in community-dwelling older veterans: prevalence of anticholinergic symptoms, symptom burden, and adverse drug events. Am J Geriatr Pharmacother 4(1):42–51
Kumpula E-K, Bell JS, Soini H, Pitkälä KH (2011) Anticholinergic drug use and mortality among residents of long-term care facilities: a prospective cohort study. J Clin Pharmacol 51(2):256–263
Gerretsen P, Pollock BG (2011) Rediscovering adverse anticholinergic effects. J Clin Psychiatry 72(6):869–870
Wilson NM, Hilmer SN, March LM, Cameron ID, Lord SR, Seibel MJ et al (2011) Associations between drug burden index and falls in older people in residential aged care. J Am Geriatr Soc 59:875–880
Fox C, Richardson K, Maidment ID, Savva GM, Matthews FE, Smithard D et al (2011) Anticholinergic medication use and cognitive impairment in the older population: The Medical Research Council Cognitive Function and Ageing Study. J Am Geriatr Soc 59:1477–1483
Carnahan RM, Lund BC, Perry PJ, Pollock BG, Culp KR (2006) The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity. J Clin Pharmacol 46:1481–1486
Ancelin ML, Artero S, Portet F, Dupuy AM, Touchon J, Ritchie K (2006) Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ 332:455–459
Chew ML, Mulsant BH, Pollock BG, Lehman ME, Greenspan A, Mahmoud RA et al (2008) Anticholinergic activity of 107 medications commonly used by older adults. J Am Geriatr Soc 56(7):1333–1341
Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE (2008) The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med 168(5):508–513
Han L, Agostini JV, Allore HG (2008) Cumulative Anticholinergic exposure is associated with poor memory and executive funtion in older men. J Am Geriatr Soc 56:2203–2210
Ehrt U, Broich K, Larsen JP, Ballard C, Aarsland D (2010) Use of drugs with anticholinergic effect and impact on cognition in Parkinson’s disease: a cohort study. J Neurol Neurosurg Psychiatry 81:160–165
Sittironnarit G, Ames D, Bush AI, Faux N, Flicker L, Foster J, Hilmer S et al (2011) Effects of anticholinergic drugs on cognitive function in older Australians: results from the AIBL Study. Dement Geriatr Cogn Disord 31:173–178
Sweetman SC (ed) (2011) Martindale: The complete drug reference. [online] Pharmaceutical Press, London <http://www.medicinescomplete.com/> (Accessed on 11–2011).
Campbell N, Boustani M, Limbil T, Ott C, Fox C, Maidment I et al (2009) The cognitive impact of anticholinergics: a clinical review. Clin Interv Aging 4:225–233
Kersten H, Molden E, Tolo IK, Skovlund E, Engedal K, Wyller TB (2013) Cognitive effects of reducing anticholinergic drug burden in a frail elderly population: a randomized controlled trial. J Gerontol A BiolSci Med Sci 68(3):271–278
Acknowledgments
We thank Thierry Christiaens and Veronika Wirtz for assistance in developing the methodology for this project.
This study was funded by a grant from the Flemish Interuniversity Council, through the University Development Cooperation (VLIR-UOS), Belgium. The funding agency was in no way implicated in the study design, data collection, analysis and interpretation, nor was there any involvement in the decision to submit the paper for publication.
Conflict of interest
None to declare
Author information
Authors and Affiliations
Corresponding author
Annex
Annex
N | Drug name | ATC 5th level | Carnahan 2006 USA | Ancelin 2006 France | Chew 2008 USA | Rudolph 2008 USA | Han 2008 USA | Ehrt 2010 Norway | Sittironnarit 2011 Australia |
---|---|---|---|---|---|---|---|---|---|
• Sublist 1. Discrepancies in drugs that received low grades, not confirmed in Martindale® (improbable anticholinergic action) | |||||||||
1 | Alverine | A03AX08 | 2 | ||||||
2 | Amoxicillin | J01CA04 | 0 | 1 | 0 | ||||
3 | Ampicillin | J01CA01 | 1 | ||||||
4 | Azathioprine | L04AX01 | 1 | ||||||
5 | Benazepril | C09AA07 | 0 | 1 | |||||
6 | Betaxolol | C07AB05 | 1 | ||||||
7 | Bisacodyl | A06AB02 | 0 | 0 | 1 | ||||
8 | Bupropion | N06AX12 | 0 | 0 | 1 | ||||
9 | Captopril | C09AA01 | 1 | 0 | 0 | ||||
10 | Carbidopa | N/A | 0 | 0 | 1 | 1 | 1 | ||
11 | Cefalexin | J01DB01 | 0 | 1 | 0 | ||||
12 | Cefamandole | J01DC03 | 1 | ||||||
13 | Cefoxitin | J01DC01 | 1 | ||||||
14 | Celecoxib | M01AH01 | 0 | 1 | 1 | ||||
15 | Cephalotin | J01DB03 | 1 | ||||||
16 | Clindamycin | J01FF01 | 1 | ||||||
17 | Cortisone | H02AB10 | 1 | ||||||
18 | Cycloserine | J04AB01 | 1 | ||||||
19 | Cyclosporine | L04AD01 | 1 | ||||||
20 | Chlorthalidone | C03BA04 | 1 | 0 | |||||
21 | Dexamethasone | H02AB02 | 1 | ||||||
22 | Dextromethorphan | R05DA09 | 1 | ||||||
23 | Diltiazem | C08DB01 | 1 | 0 | 0 | ||||
24 | Diphenoxylate | A07DA01 | 0 | 1 | 0 | ||||
25 | Dipyridamole | B01AC07 | 1 | 0 | 0 | ||||
26 | Duloxetine | N06AX21 | 0 | 1 | 0 | ||||
27 | Escitalopram | N06AB10 | 0 | 1 | 1 | ||||
28 | Estazolam | N05CD04 | 1 | ||||||
29 | Famotidine | A02BA03 | 1 | 0 | 0 | ||||
30 | Flunitrazepam | N05CD03 | 1 | ||||||
31 | Flurazepam | N05CD01 | 1 | ||||||
32 | Fluticasone-salmeterol | R03AK06 | 1 | ||||||
33 | Gentamicin | J01GB03 | 1 | ||||||
34 | Guaifenesin | R05CA03 | 0 | 1 | |||||
35 | Hydralazine | C02DB02 | 1 | 0 | |||||
36 | Hydrocortisone | H02AB09 | 1 | ||||||
37 | Isosorbidedinitrate | C01DA08 | 1 | 0 | 0 | ||||
38 | Isosorbidemononitrate | C01DA14 | 1 | 0 | 0 | ||||
39 | Ketotifenophthalmic | S01GX08 | 1 | ||||||
40 | Lansoprazole | A02BC03 | 0 | 1 | 1 | 0 | |||
41 | Levofloxacin | J01MA12 | 0 | 1 | |||||
42 | Lorazepam | N05BA06 | 1 | 0 | |||||
43 | Lumiracoxib | M01AH06 | 1 | ||||||
44 | Metformin | A10BA02 | 0 | 1 | 1 | ||||
45 | Methotrexate | L04AX03 | 0 | 1 | |||||
46 | Methylprednisolone | H02AB04 | 1 | ||||||
47 | Midazolam | N05CD08 | 1 | ||||||
48 | Naratriptan | N02CC02 | 1 | ||||||
49 | Nizatidine | A02BA04 | 1 | 0 | |||||
50 | Oxazepam | N05BA04 | 1 | 0 | 0 | 1 | |||
51 | Pancuronium | M03AC01 | 1 | ||||||
52 | Phenobarbital | N03AA02 | 0 | 1 | 1 | ||||
53 | Phenytoin | N03AB02 | 0 | 1 | |||||
54 | Piperacillin | J01CA12 | 1 | ||||||
55 | Pramipexol | N04BC05 | 0 | 1 | 0 | ||||
56 | Prednisolone | H02AB06 | 1 | 0 | |||||
57 | Pseudoephedrine | R01BA02 | 0 | 2 | |||||
58 | Selegiline | N04BD01 | 0 | 1 | 0 | ||||
59 | Sumatriptan | N02CC01 | 1 | ||||||
60 | Topiramate | N03AX11 | 0 | 1 | |||||
61 | Trandolapril | C09AA10 | 0 | 1 | |||||
62 | Triamcinolone | H02AB08 | 1 | ||||||
63 | Triamterene | C03DB02 | 1 | 0 | |||||
64 | Valproatesodium | N03AG01 | 1 | ||||||
65 | Valproicacid | N03AG01 | 1 | 0 | 0 | ||||
66 | Vancomycin | J01XA01 | 1 | ||||||
67 | Ziprasidone | N05AE04 | 0 | 1 | |||||
68 | Zolmitriptan | N02CC03 | 1 | ||||||
• Sublist 2. Drugs that received an explicit 0 in 3 out of 4 scales | |||||||||
1 | Acetylsalicylicacid | N02BA01 | 0 | 0 | 0 | 0 | |||
2 | Allopurinol | M04AA01 | 0 | 0 | 0 | ||||
3 | Amlodipine | C08CA01 | 0 | 0 | 0 | 0 | |||
4 | Atenolol | C07AB03 | 0 | 0 | 0 | 0 | |||
5 | Atorvastatin | C10AA05 | 0 | 0 | 0 | 0 | |||
6 | Carbamazepine | N03AF01 | 0 | 0 | 0 | ||||
7 | Clopidogrel | B01AC04 | 0 | 0 | 0 | ||||
8 | Donepezil | N06DA02 | 0 | 0 | 0 | ||||
9 | Enalapril | C09AA02 | 0 | 0 | 0 | 0 | |||
10 | Galantamine | N06DA04 | 0 | 0 | 0 | 0 | |||
11 | Gemfibrozil | C10AB04 | 0 | 0 | |||||
12 | Glipizide | A10BB07 | 0 | 0 | 0 | 0 | |||
13 | Haloperidol | N05AD01 | 0 | 0 | 0 | ||||
14 | Hydrochlorothiazide | C03AA03 | 0 | 0 | 0 | 0 | |||
15 | Ibuprofen | M01AE01 | 0 | 0 | 0 | 0 | |||
16 | Insulin | A10A | 0 | 0 | 0 | ||||
17 | Ketoprofen | M01AE03 | 0 | 0 | 0 | ||||
18 | Levodopa | N04BA01 | 0 | 0 | 0 | 0 | |||
19 | Lisinopril | C09AA03 | 0 | 0 | 0 | 0 | |||
20 | Losartan | C09CA01 | 0 | 0 | 0 | ||||
21 | Metoprolol | C07AB02 | 0 | 0 | 0 | 0 | |||
22 | Nifedipine | C08CA05 | 0 | 0 | 0 | ||||
23 | Nitroglycerin | C01DA02 | 0 | 0 | 0 | 0 | |||
24 | Omeprazole | A02BC01 | 0 | 0 | 0 | ||||
25 | Pantoprazole | A02BC02 | 0 | 0 | 0 | ||||
26 | Paracetamol | N02BE01 | 0 | 0 | 0 | 0 | |||
27 | Pioglitazone | A10BG03 | 0 | 0 | 0 | ||||
28 | Piroxicam | M01AC01 | 0 | 0 | 0 | ||||
29 | Propranolol | C07AA05 | 0 | 0 | 0 | ||||
30 | Rabeprazol | A02BC04 | 0 | 0 | 0 | ||||
31 | Ropinirole | N04BC04 | 0 | 0 | 0 | ||||
32 | Rosiglitazone | A10BG02 | 0 | 0 | 0 | ||||
33 | Senna | A06AB06 | 0 | 0 | 0 | ||||
34 | Sertralin | N06AB06 | 0 | 0 | 0 | ||||
35 | Simvastatin | C10AA01 | 0 | 0 | 0 | 0 | |||
36 | Spironolactone | C03DA01 | 0 | 0 | 0 | ||||
37 | Terbutaline | R03AC03 | 0 | 0 | 0 | ||||
38 | Timolol | C07AA06 | 0 | 0 | 0 | ||||
39 | Tamoxifen | L02BA01 | 0 | 0 | 0 | ||||
40 | Trimethoprim | J01EA01 | 0 | 0 | 0 | ||||
41 | Venlafaxine | N06AX16 | 0 | 0 | 0 | ||||
42 | Verapamil | C08DA01 | 0 | 0 | 0 | ||||
43 | Warfarin | B01AA03 | 0 | 0 | 0 | ||||
44 | Zolpidem | N05CF02 | 0 | 0 | 0 | ||||
45 | Zopiclone | N05CF01 | 0 | 0 | 0 |
Rights and permissions
About this article
Cite this article
Durán, C.E., Azermai, M. & Vander Stichele, R.H. Systematic review of anticholinergic risk scales in older adults. Eur J Clin Pharmacol 69, 1485–1496 (2013). https://doi.org/10.1007/s00228-013-1499-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-013-1499-3