Potentially Inadequate Medications in the Elderly: PRISCUS 2.0

First Update of the PRISCUS List

Background: The term potentially inadequate medication (PIM) is used to describe substances that may be unsuitable for use in the elderly and should be avoided. The PRISCUS list, published in 2010, was the first catalog of PIM designed for the German drug market to become adopted in practice. While 24% of German patients aged ≥ 65 years were prescribed at least one PIM per year in 2009, the proportion in 2019 was only 14.5%.

Methods: In a three-round Delphi process, experts from clinical practice and research evaluated whether selected substances are PIM for the elderly. The participants were provided with dedicated literature including systematic reviews carried out for the particular purposes of this project.

Results: Fifty-nine persons took part in the Delphi process and, in addition, contributed comments and therapeutic alternatives. Altogether, 187 substances were classed as PIM. One hundred thirty-three of the substances now listed were not in the original PRISCUS list: these include some oral antidiabetics, all of the selective COX-2 inhibitors, and moderately long acting benzodiazepines such as oxazepam. For some other substances, e.g., proton pump inhibitors (PPI), the advisability of treatment for more than 8 weeks was considered as potentially inappropriate, as was the use of ibuprofen in doses >1200 mg/day and for more than 1 week without PPI. Risperidone for more than 6 weeks is also PIM.

Conclusion: The new, greatly extended PRISCUS list must now be validated in epidemiological and prospective studies and its practicability in routine daily use must be verified.

Pharmacotherapy in the elderly has recently been addressed in national guidelines (1, 2). Along with attention to numerous factors such as patient preferences, compliance, and interactions, drug safety in old age can also be enhanced by avoidance of potentially inadequate medications (PIM). Many medications cause more—and sometimes different—side effects in the elderly than in younger patients, so the benefit–risk ratio may change. The substances primarily concerned are those that bring about dizziness or a rapid decrease in blood pressure, impair cognition, or increase the danger of falls (3, 4).

The PRISCUS list (Latin priscus: old, venerable) for the German drug market was published in 2010 (5) and has since found its way into textbooks and prescription software. Numerous studies have shown the association between the intake of PIM on the PRISCUS list and adverse drug events (ADE), in particular an elevated risk of hospital admission (6, 7, 8).

One challenge in evaluating the safety and tolerability of drugs in old age is the frequent lack of data from clinical research (9). For this reason, PIM lists are compiled by experts, usually in a Delphi process (5).

Nevertheless, it is advisable to substantiate an expert survey with the best available evidence. For an update of the PRISCUS list, additional systematic reviews should therefore be performed and existing reviews should be processed and presented to experts as the basis for maximally evidence-based decisions. The PRISCUS list is also in urgent need of updating because of the changes in the drugs market since 2010.

Method

In order to facilitate preparation of a list of substances and substance classes for evaluation, the literature was searched for international PIM lists published since 2010 and a systematic literature review was conducted (eBox 1a). To narrow down the substances for assessment, prescription data from the statutory health insurance funds in Germany and Austria were analyzed, as a joint PRISCUS 2.0 list was to be compiled for use in both countries.

eBox 1

Method

Moreover, substances were prioritized for analysis in systematic reviews on the basis of prescription frequency. We were also able to take advantage of existing reviews from the PRIMA-eDS study (an EU project; for details see www.prima-eds.eu) (9, 10, 11, 12, 13). Additionally, an exploratory survey was carried out to establish whether, for the remaining substances, information from other sources was sufficient for assessment by the participants (pre-Delphi; eBox 1b). The processing of the reviews’ findings was oriented on the standards for clinical practice guidelines (14, 15, 16). A detailed description can be found in eBox 1. Furthermore, the experts had access to a collection of literature with complete texts and abstracts from publications cited in Micromedex (17), for example, and the other publications used (eBox 1c).

The substances were evaluated on a consensus basis over a three-round Delphi process (18, 19). For this purpose, persons with expertise in geriatric pharmacotherapy were identified (professional bodies, the Drug Commission of the German Medical Association, participants in the compilation of the original PRISCUS list [5] and the Austrian PIM list [e1]) and invited to take part. The participants evaluated the substances on a five-point Likert scale, from from 1 = potentially inappropriate (= PIM) to 5 (definitely not a PIM) (eBox 2a). The rating method is explained in eBox 2b.

eBox 2

Delphi process

In addition to their ratings on the Likert scale, the participants were asked, if possible, to give the following information:

• Dose or time limit(s) from which the substance is a PIM
• More appropriate alternatives
• Monitoring of the effects if the substance is used
• Contraindicating comedication and comorbidities
• Any other comments

The participants also had the opportunity to suggest other substances for evaluation.

The results of the first Delphi round were provided to the participants as feedback (eBox 2c). Substances that were not rated unambiguously in the first round and those for which discrepancies emerged between expert evaluation and systematic reviews had to be evaluated anew in the second round. Based on the participants’ comments, some substances were evaluated in different doses and durations of use. In addition to the two Delphi rounds originally scheduled, a third round focused on one topic was added, because of inconsistencies between the evaluations and the participants’ comments with regard to the non-steroidal anti-inflammatory drugs (NSAID).

The results were available for (professional) public comment on the project website for 4 weeks in March 2021. Finally, all comments were summarized and incorporated into the complete version of PRISCUS 2.0.

Results

We identified 24 articles that listed PIM in the elderly (5, e1, e2, e3, e4, e5, e6, e7, e8, e9, e10, e11, e12, e13, e14, e15, e16, e17, e18, e19, e20, e21, e22, e23) and eight relevant systematic reviews on ADE in older patients (20, 21, 22, 23, 24, 25, 26, 27). Evaluation of the international PIM lists, the prescription data of the German National Association of Statutory Health Insurance Fund (GKV), and the substances available for use in Austria resulted in identification of a total of 250 substances and substance classes to be considered for addition to the update of the PRISCUS list. No further substances were revealed by scrutiny of the identified systematic reviews.

Thirteen systematic reviews were carried out to provide evidence backing up the suggested additions for the update of the PRISCUS list. An overview of these reviews and their roles in the project can be found in eTable 1. Altogether, 21 GRADE summary of findings (SOF) and evidence profile tables for the results of the new and identified reviews were compiled. An example of the selected presentation can be found in Table 1.

Table 1

GRADE summary of findings: PPI compared with no treatment in elderly patients

eTable 1

Overview of new and identified systematic reviews and GRADE tables

Of 101 persons contacted with regard to the Delphi process, 70 signed a declaration that they would participate. Fifty-five persons took part in the first round, 52 in the second round, and eight in the third round. Overall 59 persons took part in at least one Delphi round, representing a broad spectrum of medical specialties (including general medicine, geriatrics, clinical pharmacy, psychiatry, internal medicine, palliative medicine, clinical pharmacology, and cardiology). The distribution of the participants across the three rounds of the Delphi process is visualized in the eFigure.

eFigure

Delphi process

The three-round Delphi process began in March 2020. Of the 250 substances/substance classes evaluated in the first round, 158 were rated as PIM and 23 as non-PIM. On the basis of the expert comments, 13 substances were differentiated in terms of time/dose limits, two according to indication, one substance was added to the list, and two substances were reconsidered in their own right rather than as part of their class. Thus a total of 87 substances were put forward for assessment in the second Delphi round, 29 of which were classified as PIM and 13 as non-PIM. There was still no unambiguous rating for 45 substances. In a third Delphi round, none of the four substances evaluated were unambiguously classified as PIM or non-PIM. Over the course of the Delphi process, therefore, 187 substances were rated as PIM, 36 as non-PIM, and the classification of 49 substances was ambiguous, i.e., they may be PIM (eTable 4). The Delphi process is portrayed in the eFigure.

eTable 3

Substances classified as non-PIM

eTable 4

Substances that were classified neither as PIM nor as non-PIM

In addition to the median, mean, and 95% confidence interval, the detailed version of PRISCUS 2.0 contains the following details on each substance:

• Possible alternatives
• Information about monitoring
• Comedication/comorbidities to be avoided
• Reason for classification as PIM
• Discussion points

Substances that are no longer marketed in Germany or are not eligible for prescription are listed separately. This version is available on the project website (www.priscus2-0.de). PRISCUS 2.0 contains 177 substances/substance classes (Table 2, eTable 2).

Table 2

PRISCUS 2.0, short version

eTable 2

Substances classified as PIM (supplement to Table 2): number of ratings, mean, and confidence interval

Six substances in the original PRISCUS list were not suggested for inclusion in PRISCUS 2.0, either because they were no longer marketed (e.g., zaleplon) or because, going by the GKV prescription data, their prescription to patients aged 65 years or over had decreased to a very low level (e.g., triprolidine). Nitrofurantoin, in contrast to the original list, was no longer classified as a definite PIM. A total of 133 substances were newly classified as PIM; nine of these, however, are currently not on the market (e.g., rilmenidine) or not eligible for prescription (e.g., reboxetine).

Discussion

PRISCUS 2.0, with 177 substances listed, is more than twice as long as the original PRISCUS list. In several cases (e.g., neuroleptics and NSAID), the individual substances are listed separately rather than the substance class as a whole, in order to take account of possible differences among the substances. For some indications, such as diabetes mellitus, there was previously only one single substance listed; now numerous others have been added, not only for diabetes but also in the categories of beta-blockers, muscle relaxants, and drugs for use against Parkinson’s disease.

The need to update lists of PIM regularly because recommendations for the use of certain substances change over time can be illustrated by the example of the direct oral anticoagulants (DOAC). We conducted a systematic review specifically to clarify the safety of DOAC in the elderly. Although DOAC were not evaluated at all for the first PRISCUS list, they were classified as PIM in the EU(7) list published in 2015 (e2). In the PRISCUS 2.0 process, however, they were rated as non-PIM, with the exception of dabigatran, which was categorized as a possible PIM. In the current version of the Beers list, dabigatran and rivaroxaban are mentioned as substances that should be used with caution in the elderly (e3).

In comparison with the LUTS-FORTA list (e18), it is striking that the alpha-blockers used in urology are rated in PRISCUS 2.0 as unclear (e.g., terazosin) or as non-PIM (tamsulosin), whereas LUTS-FORTA classifies them as “use with caution” (C) or “avoid” (D). A systematic review of the safety of alpha-blockers in the elderly carried out specifically for PRISCUS 2.0 did not lead to any of them being classified as PIM (28). While oral antidiabetics such as glibenclamide, glimepiride, and acarbose were categorized as PIM, the FORTA list differentiates them: glibenclamide is classified as D, glimepiride and acarbose as C. This difference is reflected somewhat in the much lower mean rating for glibenclamide than for the other substances.

Taken together, these examples clearly illustrate the discrepancies among different lists of PIM. On the one hand, this is due to the changes in available evidence over time and the different publication times of the individual lists. On the other hand, it must be remembered that the classifications of the substances considered depend on the ratings assigned by the experts involved in the process. Differences in classification of individual substances between PIM lists may be attributable to the compositions of the groups of experts recruited.

When compiling PIM lists, other lists are often used as data sources (29). In this respect, our systematic research and the development of an adapted GRADE procedure (16) represent a considerable step forward in methodology. FORTA classifies DPP-4 inhibitors as A (absolutely suitable), whereas the systematic review conducted for PRISCUS 2.0 revealed evidence of a possible elevation in mortality risk and a slightly increased risk of hypoglycemia compared with the standard treatment; however, DPP-4 were definitely superior to the sulfonylureas (30). Nevertheless, overall this class of substances was not categorized as PIM.

Since the publication of the PRISCUS list in 2010, lists of PIM have been compiled in many other countries (29). A number of studies have shown that intake of PIM is associated with adverse effects (6, 7, 8). Although there is not yet any evidence to show that discontinuation of PIM leads to reduction of morbidity and mortality (31), some analyses show a decline in the prescription of PIM in Germany (32).

Limitations

Restricting the list of substances suggested for PRISCUS 2.0 to those found in the GKV prescription data means that substances which can be obtained without prescription or are not eligible for prescription were not considered sufficiently. One example is the antihistamine triprolidine.

It remains the case that elderly persons are often excluded from clinical trials, leading to paucity of data (33). For reasons of time and resources, we were able to conduct systematic reviews only for certain substances, so that data on the remainder were limited to the findings of non-systematic research. In contrast to the original intention, some of the systematic reviews were completed only in time for the second round of the Delphi process.

The third Delphi round, focusing on NSAID, featured fewer participants than the previous rounds. It is possible that the results of the third round would have been different if a higher number of experts had taken part. In view of the participants’ comments on which the third Delphi round was based, however, this is unlikely.

PIM lists specify substances that may not be suitable for use in the elderly. Prescription of a PIM may still be necessary in an individual patient, however, so the presence of a substance on a PIM list is not equivalent to a universally valid negative rating or prohibition. Individual assessment of each patient’s clinical situation and the resulting choice of appropriate medication is and will remain a central task for the treating physicians. Whether a given drug is suitable or otherwise for the person concerned can be decided only in the knowledge of the particular patient’s clinical situation, of which PRISCUS 2.0 takes no account. Although on the one hand this represents a crucial limitation, it means that PRISCUS 2.0 can also be used by persons with restricted access (or none at all) to clinical data, e.g., pharmacists, community carers, and relatives, to identify drugs that may not be appropriate. At various points in the medication process, therefore, it is possible to analyze—and potentially optimize—the patient’s pharmaceutical treatment in consultation and cooperation with the physicians involved. Furthermore, the PRISCUS list is useful for pharmacoepidemiological analyses in situations where clinical data are sparse (32, 34).

Funding

The study was supported by the German Federal Ministry for Education and Research (project no. BMBF 01KX1812) and by the Association of Austrian Social Insurance Funds (Dachverband der österreichischen Sozialversicherungsträger; project no. FA636A0504).

Acknowledgments

For their participation in the Delphi process, we thank the following: Eva Blozik, Birgit Böhmdorfer, Juliane Bolbrinker, Harald Dormann, Peter Dovjak, Corinna Drebenstedt, Günther Egidi, Gottfried Endel, Heinz Endres, Alexander Friedl, Thomas Frühwald, Gerald Ohrenberger, Markus Gosch, Athe Grafinger, Gerhard Gründer, Thomas Günnewig, Walter E. Haefeli, Ekkehard Haen, Sebastian Harder, Steffen Härterich, Siegfried Hartmann, Hans Jürgen Heppner, Walter Hewer, Christine Hofer-Dückelmann, Ulrich Jaehde, Petra Kaufmann-Kolle, Rainer Kiefmann, Michael Klock, Karin Kraft, Reinhold Kreutz, Renke Maas, Eva Mann, Werner-J. Mayet, Reli Mechtler, Guido Michels, Veselin Mitrovic, Klaus Mörike, Ursula Müller-Werdan, Beate Mussawy, Wilhelm-Bernhard Niebling, Roman Pfister, Susanne Rabady, Ina Richling, Thomas Riemer, Christoph Ritter, Martin Scherer, Guido Schmiemann, Jochen Schuler, Oliver Senn, Michael Smeikal, Isabel Waltering, Dietmar Weixler, Andreas Wiedemann, Hans Wille, Stefan Wilm, Rainer Wirth, Ursula Wolf, Joachim Zeeh, Michael Zieschang.

Für supporting our project in other ways, we thank: Tobias Dreischulte, Birol Knecht, Katja Niepraschk-von Dollen, Helmut Schröder, Carsten Telschow, Anette Zawinell.

Conflict of interest statement

The authors declare that no conflict of interest exists.

Manuscript received on 12 September 2022, revised version accepted on 9 November 2022.

Translated from the original German by David Roseveare.

Corresponding author
Prof. Dr. med. Petra A. Thürmann
Lehrstuhl für Klinische Pharmakologie
Department für Humanmedizin
Fakultät für Gesundheit, Universität Witten/Herdecke
Alfred-Herrhausen-Str. 50
58455 Witten, Germany

Cite this as:
Mann NK, Mathes T, Sönnichsen A, Pieper D, Klager E, Moussa M, Thürmann PA: Potentially inadequate medications in the elderly: PRISCUS 2.0—first update of the PRISCUS list. Dtsch Arztebl Int 2023; 120: 3–10. DOI: 10.3238/arztebl.m2022.0377

►Supplemenary material

eReferences, eTables, eFigure, eBoxes:
www.aerzteblatt-international.de/m2022.0377

References

1. Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin: Multimorbidität. S3-Leitlinie. DEGAM-Leitlinie Nr. 20. 2017. https://www.degam.de/files/Inhalte/Leitlinien-Inhalte/Dokumente/DEGAM-S3-Leitlinien/053-047_Multimorbiditaet/053-047l_%20Multimorbiditaet_redakt_24-1-18.pdf (last accessed on 30 November 2022).

2. Pharmakotherapie LHH: Hausärztliche Leitlinie Multimedikation, Version 2.00. 2021.

3. Shi S, Morike K, Klotz U: The clinical implications of ageing for rational drug therapy. Eur J Clin Pharmacol 2008; 64: 183–99

4. Davies EA, O‘Mahony MS: Adverse drug reactions in special populations—the elderly. Br J Clin Pharmacol 2015; 80: 796–807

5. Holt S, Schmiedl S, Thurmann PA: Potentially inappropriate medications in the elderly: the PRISCUS list. Dtsch Arztebl Int 2010; 107: 543–51

6. Endres HG, Kaufmann-Kolle P, Steeb V, Bauer E, Bottner C, Thurmann P: Association between Potentially Inappropriate Medication (PIM) use and risk of hospitalization in older adults: an observational study based on routine data comparing PIM use with use of PIM alternatives. PloS One 2016; 11: e0146811

7. Henschel F, Redaelli M, Siegel M, Stock S: Correlation of incident potentially inappropriate medication prescriptions and hospitalization: an analysis based on the PRISCUS list. Drugs Real World Outcomes 2015; 2: 249–59

8. Bauer TK, Lindenbaum K, Stroka MA, Engel S, Linder R, Verheyen F: Fall risk increasing drugs and injuries of the frail elderly—evidence from administrative data. Pharmacoepidemiol Drug Saf 2012; 21: 1321–7

9. Martinez YV, Renom-Guiteras A, Reeves D, et al.: A set of systematic reviews to help reduce inappropriate prescribing to older people: study protocol. BMC Geriatr 2017; 17: 231

10. Schott G, Martinez YV, Ediriweera de Silva RE, et al.: Effectiveness and safety of dipeptidyl peptidase 4 inhibitors in the management of type 2 diabetes in older adults: a systematic review and development of recommendations to reduce inappropriate prescribing. BMC Geriatr 2017; 17: 226

11. Schlender L, Martinez YV, Adeniji C, et al.: Efficacy and safety of metformin in the management of type 2 diabetes mellitus in older adults: a systematic review for the development of recommendations to reduce potentially inappropriate prescribing. BMC Geriatr 2017; 17: 227

12. Vogele A, Johansson T, Renom-Guiteras A, et al.: Effectiveness and safety of beta blockers in the management of hypertension in older adults: a systematic review to help reduce inappropriate prescribing. BMC Geriatr 2017; 17: 224

13. Sommerauer C, Schlender L, Krause M, et al.: Effectiveness and safety of vitamin K antagonists and new anticoagulants in the prevention of thromboembolism in atrial fibrillation in older adults—a systematic review of reviews and the development of recommendations to reduce inappropriate prescribing. BMC Geriatr 2017; 17: 223

14. Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF): AWMF-Regelwerk Leitlinien 2020.

15. Langer G, Meerpohl JJ, Perleth M, Gartlehner G, Kaminski-Hartenthaler A, Schunemann H: [GRADE guidelines: 1. Introduction—GRADE evidence profiles and summary of findings tables]. Z Evid Fortbild Qual Gesundhewes 2012; 106: 357–68

16. Mathes T, Mann N-K, Thürmann P, Sönnichsen A, Pieper D: Assessing the quality of evidence on safety: specifications for application and suggestions for adaptions of the GRADE-criteria in the context of preparing a list of potentially inappropriate medications for older adults. BMC Med Res Methodol 2022; 22: 234

17. IBM: Micromedex. www.ibm.com/watson-health/about/micromedex (last accessed on 30 November 2022).

18. Boulkedid R, Abdoul H, Loustau M, Sibony O, Alberti C: Using and reporting the Delphi method for selecting healthcare quality indicators: a systematic review. PloS One 2011; 6: e20476

19. Diamond IR, Grant RC, Feldman BM, et al.: Defining consensus: a systematic review recommends methodologic criteria for reporting of Delphi studies. J Clin Epidemiol 2014; 67: 401–9

20. Farooqi V, van den Berg ME, Cameron ID, Crotty M: Anabolic steroids for rehabilitation after hip fracture in older people. Cochrane Database Syst Rev 2014; 2014: CD008887

21. Schneider-Thoma J, Efthimiou O, Bighelli I, et al.: Second-generation antipsychotic drugs and short-term somatic serious adverse events: a systematic review and meta-analysis. Lancet Psychiatry 2019; 6: 753–65

22. Ahmed H, Davies F, Francis N, Farewell D, Butler C, Paranjothy S: Long-term antibiotics for prevention of recurrent urinary tract infection in older adults: systematic review and meta-analysis of randomised trials. BMJ Open 2017; 7: e015233

23. Bloch F, Thibaud M, Dugué B, Brèque C, Rigaud AS, Kemoun G: Laxatives as a risk factor for iatrogenic falls in elderly subjects: myth or reality? Drugs Aging 2010; 27: 895–901

24. Cho H, Myung J, Suh HS, Kang HY: Antihistamine use and the risk of injurious falls or fracture in elderly patients: a systematic review and meta-analysis. Osteoporos Int 2018; 29: 2163–70

25. Lee PE, Gill SS, Freedman M, Bronskill SE, Hillmer MP, Rochon PA: Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review. BMJ 2004; 329: 75

26. Schneider-Thoma J, Efthimiou O, Huhn M, et al.: Second-generation antipsychotic drugs and short-term mortality: a systematic review and meta-analysis of placebo-controlled randomised controlled trials. Lancet Psychiatry 2018; 5: 653–63

27. Tham A, Jonsson U, Andersson G, Söderlund A, Allard P, Bertilsson G: Efficacy and tolerability of antidepressants in people aged 65 years or older with major depressive disorder—a systematic review and a meta-analysis. J Affect Disord 2016; 205: 1–12

28. Mansbart F, Kienberger G, Sönnichsen A, Mann E: Efficacy and safety of adrenergic alpha-1 receptor antagonists in older adults: a systematic review and meta-analysis for the development of recommendations to reduce potentially inappropriate prescribing. PREPRINT (Version 1). Research Square 2022. www.europepmc.org/article/PPR/PPR440769 (last accessed on 30 November 2022)

29. Motter FR, Fritzen JS, Hilmer SN, Paniz ÉV, Paniz VMV: Potentially inappropriate medication in the elderly: a systematic review of validated explicit criteria. Eur J Clin Pharmacol 2018; 74: 679–700

30. Doni K, Bühn S, Weise A, et al.: Safety of dipeptidyl peptidase-4 inhibitors in older adults with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Ther Adv Drug Saf 2022; 13: 20420986211072383

31. Rudolf H, Thiem U, Aust K, et al.: Reduction of potentially inappropriate medication in the elderly—results of a cluster-randomized, controlled trial in German primary care practices (RIME). Dtsch Arztebl Int 2021; 118: 875–82

32. Selke Krulichová I, Selke GW, Thürmann PA: Trends and patterns in EU(7)-PIM prescribing to elderly patients in Germany. Eur J Clin Pharmacol 2021 77: 1553–61

33. Florisson S, Aagesen EK, Bertelsen AS, Nielsen LP, Rosholm JU: Are older adults insufficiently included in clinical trials?—an umbrella review. Basic Clin Pharmacol Toxicol 2021; 128: 213–23

34. Scherag A, Andrikyan W, Dreischulte T, et al.: POLAR – „POLypharmazie, Arzneimittelwechselwirkungen und Risiken“ – wie können Daten aus der stationären Krankenversorgung zur Beurteilung beitragen?. Präv Gesundheitsf (2022). doi.org/10.1007/s11553-022-00976-8.

e1. Mann E, Bohmdorfer B, Fruhwald T, et al.: Potentially inappropriate medication in geriatric patients: the Austrian consensus panel list. Wien Klin Wochenschr 2012; 124: 160–9

e2. Renom-Guiteras A, Meyer G, Thurmann PA: The EU(7)-PIM list: a list of potentially inappropriate medications for older people consented by experts from seven European countries. Eur J Clin Pharmacol 2015; 71: 861–75

e3. By the 2019 American Geriatrics Society Beers Criteria Update Expert Panel: American Geriatrics Society 2019 Updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019; 67: 674–94

e4. By the American Geriatrics Society 2015 Beers Criteria Update Expert Panel: American Geriatrics Society 2015 Updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2015; 63: 2227–46

e5. American Geriatrics Society 2012 Beers Criteria Update Expert Panel: American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2012; 60: 616–31

e6. Chang CB, Yang SY, Lai HY, et al.: Using published criteria to develop a list of potentially inappropriate medications for elderly patients in Taiwan. Pharmacoepidemiol Drug Saf 2012; 21: 1269–79

e7. Chang CB, Lai HY, Hwang SJ, et al.: The updated PIM-Taiwan criteria: a list of potentially inappropriate medications in older people. Ther Adv Chronic Dis 2019; 10: 2040622319879602

e8. Clyne B, Bradley MC, Hughes CM, et al.: Addressing potentially inappropriate prescribing in older patients: development and pilot study of an intervention in primary care (the OPTI-SCRIPT study). BMC Health Serv Res 2013; 13: 307

e9. Fimea FMA: Meds75 Database of Medications for Older Persons. 2020. www.fimea.fi/web/en/databases_and_registeries/medicines_information/database_of_medication_for_older_persons (last accessed on 19 December 2022).

e10. Khodyakov D, Ochoa A, Olivieri-Mui BL, et al.: Screening tool of older person‘s prescriptions/screening tools to alert doctors to right treatment medication criteria modified for U.S. nursing home setting. J Am Geriatr Soc 2017; 65: 586–91

e11. Kim DS, Heo SI, Lee SH: Development of a list of potentially inappropriate drugs for the korean elderly using the Delphi method. Healthc Inform Res 2010; 16: 231–52

e12. Kim SO, Jang S, Kim CM, Kim YR, Sohn HS: Consensus validated list of potentially inappropriate medication for the elderly and their prevalence in South Korea. Int J Gerontol 2015; 9: 136–41

e13. Kojima T, Mizukami K, Tomita N, et al.: Screening tool for older persons‘ appropriate prescriptions for Japanese: report of the Japan Geriatrics Society Working Group on „Guidelines for medical treatment and its safety in the elderly“. Geriatr Gerontol Int 2016; 16: 983–1001

e14. Kuhn-Thiel AM, Weiss C, Wehling M: Consensus validation of the FORTA (Fit fOR The Aged) list: a clinical tool for increasing the appropriateness of pharmacotherapy in the elderly. Drugs Aging 2014; 31: 131–40

e15. Maio V, Del Canale S, Abouzaid S: Using explicit criteria to evaluate the quality of prescribing in elderly Italian outpatients: a cohort study. J Clin Pharm Ther 2010; 35: 219–29

e16. Mazhar F, Akram S, Malhi SM, Haider N: A prevalence study of potentially inappropriate medications use in hospitalized Pakistani elderly. Aging Clin Exp Res 2018; 30: 53–60

e17. Nyborg G, Straand J, Klovning A, Brekke M: The Norwegian General Practice—Nursing Home criteria (NORGEP-NH) for potentially inappropriate medication use: a web-based Delphi study. Scand J Prim Health Care 2015; 33: 134–41

e18. Oelke M, Becher K, Castro-Diaz D, et al.: Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014). Age Ageing 2015; 44: 745–55

e19. O‘Mahony D, O‘Sullivan D, Byrne S, O‘Connor MN, Ryan C, Gallagher P: STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing 2015; 44: 213–8

e20. Pazan F, Weiss C, Wehling M: The FORTA (Fit fOR The Aged) List 2015: update of a validated clinical tool for improved pharmacotherapy in the elderly. Drugs Aging 2016; 33: 447–9

e21. Pazan F, Weiss C, Wehling M: The EURO-FORTA (Fit fOR The Aged) List: International consensus validation of a clinical tool for improved drug treatment in older people. Drugs Aging 2018; 35: 61–71

e22. Pazan F, Weiss C, Wehling M: The FORTA (Fit fOR The Aged) List 2018: third version of a validated clinical tool for improved drug treatment in older people. Drugs Aging 2019; 36: 481–4

e23. Tommelein E, Petrovic M, Somers A, Mehuys E, van der Cammen T, Boussery K: Older patients‘ prescriptions screening in the community pharmacy: development of the Ghent Older People‘s Prescriptions community Pharmacy Screening (GheOP(3)S) tool. J Public Health (Oxf) 2016; 38: e158–70

e24. Miyamoto M, Haruma K, Kuwabara M, Nagano M, Okamoto T, Tanaka M: Long-term gastroesophageal reflux disease therapy improves reflux symptoms in elderly patients: five-year prospective study in community medicine. J Gastroenterol Hepatol 2007; 22: 639–44

e25. Maggio M, Corsonello A, Ceda GP, et al.: Proton pump inhibitors and risk of 1-year mortality and rehospitalization in older patients discharged from acute care hospitals. JAMA Intern Med 2013; 173: 518–23

e26. Shah S, Lewis A, Leopold D, Dunstan F, Woodhouse K: Gastric acid suppression does not promote clostridial diarrhoea in the elderly. QJM 2000; 93: 175–81

e27. Yearsley KA, Gilby LJ, Ramadas AV, Kubiak EM, Fone DL, Allison MC: Proton pump inhibitor therapy is a risk factor for Clostridium difficile associated diarrhoea. Aliment Pharmacol Ther 2006; 24: 613–19

e28. Yang YX, Lewis JD, Epstein S, Metz DC: Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 2006; 296: 2947–53

e29. Haenisch B, von Holt K, Wiese B, et al.: Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci 2015; 265: 419–28

e30. Herghelegiu AM, Prada GI, Nacu R: Prolonged use of proton pump inhibitors and cognitive function in older adults. Farmacia 2016; 64: 262–7.

e31. Gomm W, von Holt K, Thomé F, et al.: Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis. JAMA Neurol 2016; 73: 410–6

e32. Gray SL, Walker RL, Dublin S, et al.: Proton pump inhibitor use and dementia risk: prospective population-based study. J Am Geriatr Soc 2018; 66: 247–53

e33. Goldstein FC, Steenland K, Zhao L, Wharton W, Levey AI, Hajjar I: Proton pump inhibitors and risk of mild cognitive impairment and dementia. Am Geriatr Soc 2017; 65: 1969–74

e34. Antoniou T, Macdonald EM, Hollands S, et al.: Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ 2015; 3: E166–E71

e35. Kiesel EK, Hopf YM, Drey M: An anticholinergic burden score for German prescribers: score development. BMC Geriatr 2018; 18: 239