European Geriatric Medicine (2021) 12:431–434

https://doi.org/10.1007/s41999-021-00493-5

EDITORIAL

Mastering the complexity: drug therapy optimization in geriatric

Published online: 8 April 2021

The management of pharmacological therapy in older into personalized prescribing remains a hypothetical con-
patients is challenging in clinical practice. Older subjects struct in geriatric care. In anticipation of the inclusion of
experience age-related changes that influence pharmacoki- frail and complex older patients in pre- and post-marketing
netics and pharmacodynamics of drugs, they also usually studies, a better understanding of the key pharmacokinetic
have multiple diseases, i.e., multimorbidity, and are often alterations of common medications in “real-life” patients,
cared for, and hence, prescribed by a number of physicians together with the implementation of effective strategies
over a long period of time. Therefore, it is not surprising tackling inappropriate prescribing, is likely to improve clini-
that polypharmacy, literally the use of multiple drugs, is cal outcomes and reduce healthcare utilization in the older
extremely common in older patients and is increasing over population.
time, at least in developed countries [1, 2]. In the paper on definition, epidemiology and conse-
Appropriate geriatric pharmacotherapy, global assess- quences of polypharmacy, Pazan et al. show that there is no
ment of patients’ clinical and functional parameters, and universally accepted definition of polypharmacy [4]. While
integration of skills from different healthcare professionals many different definitions have been used, the majority only
are needed to address the medical complexity of older adults. consider the number of drugs. The most common one is
In this special issue, the most relevant aspects of pharma- based on treatment with five or more drugs. This concept is
cotherapy in older people have been addressed. not very useful as a relevant problem with the use of multi-
In the paper discussing drug metabolism and elimination ple drugs is the frequent presence of inappropriate drugs. On
in older people in the perspective of personalized prescrip- this premise, it has been proposed to focus on problematic
tion, Mangoni and Jarmuzewska review the current evidence or unnecessary rather than appropriate polypharmacy [5,
regarding the main age-associated changes in drug metabo- 6]. The heterogeneity of definitions might also be responsi-
lism and elimination and elaborate on their possible inclu- ble for the controversial relationship of polypharmacy with
sion in current and future personalized prescribing tools for negative clinical outcomes in different studies. Neverthe-
older patients [3]. The integration of pharmacokinetic data less, the association of polypharmacy with geriatric condi-
tions, such as frailty, falls, physical function and cognitive
impairment as well as with hospitalization, mortality has
* A. Cherubini been documented in multiple studies. WHO declared that
[email protected] polypharmacy is a relevant target to address to increase
1 patient safety [7].
Geriatria, Accettazione Geriatrica e Centro di ricerca
per l’invecchiamento, IRCCS INRCA​, Ancona, Italy Cherubini et al. address the causes and consequences of
2 underprescription of medications in older adults. They show
Centre de Pharmacovigilance, de Pharmacoépidémiologie et
D’information sur les Médicaments, Centre de Biologie et de that despite the fact that polypharmacy is widespread, there
Recherche en Santé, Service de Pharmacologie, Toxicologie are multiple studies illustrating that many older subjects are
et Pharmacovigilance, CHU de Limoges, Limoges, France not treated with drugs appropriate for their disease, a condi-
3
Université de Limoges, INSERM 1248, Faculté de Médecine, tion known as underprescription [8]. Among the medicines
Limoges, France most commonly underprescribed, there are cardiovascular
4
Université de Limoges, Unité Vie-Santé, Faculté de drugs, e.g., ace inhibitors and statins, anticoagulants and
Médecine, Limoges, France anti-osteoporosis drugs. The consequences of underpre-
5
Department of Internal Medicine and Paediatrics, Section scription are relevant for patients and healthcare systems,
of Geriatrics, Ghent University, Ghent, Belgium

13
Vol.:(0123456789)
432 European Geriatric Medicine (2021) 12:431–434

in terms of higher risks of cardiovascular events, disability, the drugs, compared to the comprehensive geriatric assess-
hospitalization and death. While some studies showed that ment which demonstrates a better identification of patients at
interventions based on the implementation of explicit crite- risk of ADR occurrence and also takes more into account the
ria for underprescription, comprehensive geriatric assess- care objectives and the patients’ needs. The authors advocate
ment by geriatricians, as well as the involvement of a clinical a multidimensional and holistic approach combining phar-
pharmacist can reduce underprescription, the improvement maceutical interventions with a global evaluation of health
of clinical outcomes has not yet been convincingly dem- needs and priorities to reduce the burden of ADRs in older
onstrated. Furthermore, there is still need for high-quality adults.
research with a more in-depth analysis of the causes of In the next paper of this special issue, Rochon et al. focus
underprescription that in some cases might be correct, e.g., on prescribing cascades as a phenomenon closely associated
when patients are allergic or intolerant to the drug or the lag with polypharmacy [12]. The use of multiple drugs is often
time needed for a specific drug to be beneficial is longer than associated with the occurrence of side effects, which might
the estimated life expectancy of a patient. be misinterpreted as new symptoms or clinical events and
Capiau et al. elaborate on a guidance for appropriate use lead to the prescription of new drugs to treat them. Research
of psychotropic drugs, as the most prescribed drug class in in this field is still relatively new, and therefore, the preva-
older people [9]. They emphasize that the appropriate use lence and clinical relevance of prescribing cascades have not
of these drugs in older people can be optimized in terms yet been systematically established. Moreover, the presence
of various aspects, such as indications, contraindications, of differences related to sex and gender in the occurrence
dosing, adverse drug reactions, interactions and duration of and consequences of this condition are currently unknown.
therapy. Different strategies and practical recommendations To provide a better knowledge of prescribing cascades
should be considered to increase the appropriate use of these focusing specifically on sex and gender, is the aim of the
medications in older people. The importance of a multifac- iKascade project, an international research project whose
eted approach including non-pharmacological interventions, rationale and design are presented here. The project involves
comprehensive medication reviews, shared decision-making an international team of experts led by Paula Rochon, a geri-
and close interprofessional communication and collabora- atrician and expert in gender medicine from Canada.
tion is highlighted. In the paper on fall risk-inducing drugs, van der Velde
In the paper on potentially inappropriate medication et al. point out that falls are a geriatric syndrome that often
use among older people with dementia, Renom Guiteras have a dramatic impact on health and the level of autonomy
discusses several aspects that are considered when patient of older subjects [13]. Falls represent an important cause of
tailoring decisions are made on the pharmacotherapy appro- fractures, head trauma and mortality in older subjects and,
priateness among older people with dementia [10]. The even when they do not determine immediate negative con-
aspects that may deserve special consideration include the sequences, they can induce a fear of falling, leading to social
prescription of psychotropic medications, for being com- isolation, immobility and, paradoxically, an increased risk of
monly inappropriately prescribed; the presence of advanced falling. Falls are typically multifactorial and several drugs,
stage of dementia, comorbidities or multimorbidity and/or named fall risk increasing drugs (FRID), can contribute to
frailty, as they can determine the prognosis and goals of increase the probability of experiencing a fall. The Euro-
care; the values and wishes of the person with dementia, pean Geriatric Medicine Society working groups produced
as they may prioritize different goals of care; and medica- an explicit tool to identify FRID (STOPFALL) together with
tion adherence, as it may be poorer compared with persons guidance to support an evidence-based approach in depre-
without dementia. These individualized decisions require a scribing these drugs [14] Among FRID, there are also anti-
comprehensive evaluation of the patient. The need for stud- depressants, which can contribute to increase the risk of fall-
ies including representative study participants and further ing with different mechanisms, including sedation, delirium,
evidence-based guidelines are necessary to support these hyponatraemia, orthostatic hypotension, cardiac side effects
decisions. and impaired mobility. On the other hand, depression has
Zazzara et al. address the important topic of adverse drug several negative consequences in older adults and increases
reactions (ADRs). ADRs are frequent in older adults and are the risk of falling. Therefore, a careful evaluation of the indi-
often related to commonly used medications [11]. Certain vidual risk benefit ratio should be made when deciding the
risk factors for the occurrence of ADRs are uncontrolla- prescription or continuation of antidepressant therapy, par-
ble, but others can be dealt with better by considering the ticularly in older people who are at increased risk of falling.
older patients in their complexity. The authors show that When appropriate, deprescribing should be pursued accord-
approaches such as medication review, software identifying ing to the available evidence and specific expertise.
potentially inappropriate prescriptions, are sometimes disap- In the paper written by Laroche et al., the fundamentals
pointing in ADR prevention because they are too focused on of drug-related problems (DRPs) in older adults are put

13
European Geriatric Medicine (2021) 12:431–434 433

in perspective according to a logical process, conciliating polymedicated patients with regard to health-related out-
medical and pharmaceutical approaches to better identify comes and that better-designed studies are warranted in the
the causes and consequences of DRPs [15]. This process future to provide further insights into the effect of hospitals
analysis is carried out at the physician, pharmacist, nurses pharmacists interventions.
and patient level, to understand the phenomenon of DRPs, Finally, in the paper on the use of opioids in the geriatric
to prevent the consequences leading to negative benefit/risk patient at the end of life, Janssens et al. describe pharmaco-
ratio of drugs, and to identify corrective actions to improve logical treatment at the end of life, comparing use and dos-
medication use among older people. This overview shows age of opioids in the acute geriatric ward and palliative care
that medication errors are not the most frequent cause of unit, pointing out that achieving adequate symptom control
DRPs. Surprisingly, substance use disorders are rarely is related to the use of opioids [19].
studied in older adults and need to be investigated further In this special issue, the most relevant aspects of geriatric
because the use of psychoactive substances among older pharmacotherapy are presented and critically discussed. The
people is frequent. Finally, to prevent DRPs in older adults, optimal management of drugs in older patients is a corner-
improved communication between healthcare professionals, stone of the practice of geriatric medicine and one of the
patients and their carers would ensure greater safety and most important contributions to the evolution of health care
effectiveness of treatments. in the direction of adapting contemporary clinical practice
Beuscart et al. explain that medication reconciliation to the specific needs of older patients. However, while the
(MedRec) and review (MedRev) are complementary in pre- tasks are clear, i.e., tailoring drug therapy according to the
venting medication-related problems in older adults [16]. personal preferences and characteristics, increase patient
These strategies are successful because they integrate the safety by reducing adverse drug reactions, achieve the most
skills of different health care professionals who have to deal favorable risk benefit ratio for each patient, periodically
with the medical complexities of older patients. However, reviewing pharmacological therapy including deprescrib-
these procedures are time-consuming and require a perfect ing, as appropriate, the implementation in practise is often
coordination of all the different healthcare professionals. difficult, particularly when health care professionals are not
Information technology (IT) can be considered as an assis- geriatricians or clinical pharmacists.
tance for MedRec or MedRev, by means of an automatic A research priority is, therefore, to develop and validate
data analysis. The authors insist on the paradigm shift that interventions that can be applied by healthcare profession-
healthcare professionals in geriatrics must do: from a dis- als who are not highly skilled in geriatric pharmacotherapy.
ease-centered approach to patient-centered care, communi- The recently published results of the SENATOR trial, a large
cation and shared decision-making. randomized clinical trial which failed to achieve a reduction
Spinewine et al. describe strategies and interventions to of adverse drug reactions by means of a highly sophisticated
optimize medication use in nursing homes. The authors car- software aimed at optimizing pharmacotherapy in hospital-
ried out a two-level analysis of the health care system [17]. ized older patients, confirm the persistence of this important
For the personnel and residents, medication review, mul- unmet need [20].
tidisciplinary work and patient-centered care are the main
approaches proven to be effective in nursing homes. How-
ever, there is a large heterogeneity in the outcomes across
the studies. It would be preferable to use core outcome sets Compliance with ethical standards
focused on nursing home residents or multimorbid older
adults. At the system-level, legislations and underperform- Conflict of interest The Authors declare no conflict of interest.
ing care networks are the main barriers holding up optimal Ethics approval Ethical approval is not required for this manuscript.
implementation of procedures, with a crucial need for fund-
ing, especially in Europe. Informed consent Informed consent is not required for this manuscript.
In the paper on effectiveness of hospital pharmacists in
improving drug therapy and relevant health outcomes, Del-
gado et al. review the current evidence regarding the effects References
of interventions by hospital pharmacists, individually or
in collaboration with a multidisciplinary team, in terms 1. Qato DM, Wilder J, Schumm LP, Gillet V, Alexander GC (2016)
of healthcare outcomes, effective utilization of resources Changes in prescription and over-the-counter medication and
and lower costs in older patients with multimorbidity and dietary supplement use among older adults in the United States,
2005 vs 2011. JAMA Intern Med 176(4):473–482. https://d​ oi.o​ rg/​
polypharmacy [18]. They conclude that so far there is no 10.​1001/​jamai​ntern​med.​2015.​8581
hard evidence that demonstrates the effectiveness of hos- 2. Zhang N, Sundquist J, Sundquist K, Ji J (2020) An increasing
pital pharmacists’ interventions in older multimorbid and trend in the prevalence of polypharmacy in Sweden: a nationwide

13
434 European Geriatric Medicine (2021) 12:431–434

register-based study. Front Pharmacol 11:326. https://​doi.​org/​10.​ Landi F, Morrissey Y, Mair A, Gutiérrez-Valencia M, Emmelot-
3389/​fphar.​2020.​00326 Vonk MH, Mora MÁC, Denkinger M, Crome P, Jackson SHD,
3. Mangoni AA, Jarmuzewska EA (2021) Incorporating pharma- Correa-Pérez A, Knol W, Soulis G, Gudmundsson A, Ziere G,
cokinetic data into personalised prescribing for older people: Wehling M, O’Mahony D, Cherubini A, van der Velde N (2020)
challenges and opportunities. Eur Geriatr Med. https://​doi.​org/​ STOPPFall (screening tool of older persons prescriptions in older
10.​1007/​s41999-​020-​00437-5 (Epub ahead of print) adults with high fall risk): a Delphi study by the EuGMS task and
4. Pazan F, Wehling M (2021) Polypharmacy in older adults: a nar- finish group on fall-risk-increasing drugs. Age Ageing 22:afaa249.
rative review of definitions, epidemiology and consequences. Eur https://​doi.​org/​10.​1093/​ageing/​afaa2​49.
Geriatr Med. https://d​ oi.o​ rg/1​ 0.1​ 007/s​ 41999-0​ 21-0​ 0479-3 (Epub 15. Laroche ML, Thi Hong Van Ngo, Sirois C, Daveluy A, Guillaumin
ahead of print) M, Valnet-Rabier MB, Grau M, Roux B, Merle L (2021) Mapping
5. Scottish Government Polypharmacy Model of Care Group. Poly- of drug-related problems among older adults conciliating medical
pharmacy Guidance, Realistic Prescribing 3rd Edition, 2018. and pharmaceutical approaches. Eur Geriat Med (in press).
Scottish Government https://​www.​thera​peuti​cs.​scot.​nhs.​uk/​wp-​ 16. Beuscart JB, Pelayo S, Robert L, Thevelin S, Marien S, Dalleur O
conte​nt/​uploa​ds/​2018/​04/​Polyp​harma​cy-​Guida​nce-​2018.​pdf Last (2021) Medication review and reconciliation in older adults. Eur
accessed on March 1st, 2021 Geriatr Med. https://​doi.​org/​10.​1007/​s41999-​021-​00449-9.
6. Gutiérrez-Valencia M, Martínez-Velilla N, Vilches-Moraga A 17. Spinewine A, Evrard P, Hughes C (2021) Interventions to opti-
(2019) Polypharmacy in older people: time to take action. Eur mize medication use in nursing homes. A narrative review. Eur
Geriatr Med 10(1):1–3 Geriat Med (in press).
7. Medication Safety in Polypharmacy. Geneva: World Health 18. Delgado-Silveira E, Vélez-Díaz-Pallarés M, Muñoz-García M,
Organization 2019 (WHO/UHC/SDS/2019.11). https://​apps.​who.​ Correa-Pérez A, Álvarez-Díaz AM, Cruz-Jentoft AJ (2021)
int/​iris/​bitst​ream/​handle/​10665/​325454/​WHO-​UHC-​SDS-​2019.​ Effects of hospital pharmacist interventions on health outcomes
11-​eng.​pdf?​ua=1 last accessed March 1st, 2021 in older polymedicated inpatients: a scoping review. Eur Geriat
8. Lombardi F, Paoletti L, Carrieri B, Dell’Aquila G, Fedecostante Med (in press).
M, Di Muzio M, Corsonello A, Lattanzio F, Cherubini A (2021) 19. Jannens W, Van Den Noortgate NJ, Piers RD (2021) Pharmaco-
Underprescription of medications in older adults: causes, conse- logical treatment in the dying geriatric patient: describing use and
quences and solutions-a narrative review. Eur Geriatr Med. https://​ dosage of opioids in the acute geriatric wards and palliative care
doi.​org/​10.​1007/​s41999-​021-​00471-x. (Epub ahead of print) units of 3 hospitals. Eur Geriat Med (in press).
9. Capiau A, Foubert K, Somers A, Petrovic M (2021) Guidance for 20. O’Mahony D, Gudmundsson A, Soiza RL, Petrovic M, Jose Cruz-
appropriate use of psychotropic drugs in older people. Eur Geriatr Jentoft A, Cherubini A, Fordham R, Byrne S, Dahly D, Gallagher
Med. https://​doi.​org/​10.​1007/​s41999-​020-​00439-3 (Epub ahead P, Lavan A, Curtin D, Dalton K, Cullinan S, Flanagan E, Shiely F,
of print). Samuelsson O, Sverrisdottir A, Subbarayan S, Vandaele L, Meire-
10. Renom Guiteras A (2021) Potentially inappropriate medication son E, Montero-Errasquin B, Rexach-Cano A, Correa Perez A,
among people with dementia: towards individualized decision- Lozano-Montoya I, Vélez-Díaz-Pallarés M, Cerenzia A, Corradi
making. Eur Geriat Med (in press). S, Soledad Cotorruelo Ferreiro M, Dimitri F, Marinelli P, Martelli
11. Zazzara MB, Palmer K, Vetrano D, Carfi A, Onder G (2021) G, Fong Soe Khioe R, Eustace J (2020) Prevention of adverse
Adverse drug reactions in older adults: a narrative review of the drug reactions in hospitalized older patients with multi-morbidity
literature. Eur Geriat Med (in press) and polypharmacy: the SENATOR* randomized controlled clini-
12. Shelley A, Sternberg SA, Petrovic M, Onder G, Cherubini A, cal trial. Age Ageing 49(4):605–614. https://​doi.​org/​10.​1093/​age-
O’Mahony D, Gurwitz J, Pegreffi F, Mason R, Akerman J, McCa- ing/​afaa0​72
rthy L, Lawson A, Li J, Wu W, Rochon P (2021) Identifying key
prescribing cascades in older people (iKascade): a transnational Publisher’s Note Springer Nature remains neutral with regard to
initiative on drug safety through a sex and gender lens—rationale jurisdictional claims in published maps and institutional affiliations.
and design. Eur Geriat Med (in press).
13. van Poelgeest EP, Pronk A, Rhebergen D, van der Velde N (2021)
Depression, antidepressants and fall risk: therapeutic dilemmas.
A clinical review. Eur Geriat Med (in press)
14. Seppala LJ, Petrovic M, Ryg J, Bahat G, Topinkova E,
Szczerbińska K, van der Cammen TJM, Hartikainen S, Ilhan B,

13