Polypharmacy is a rapidly growing problem. It mainly affects geriatric patients. Multimorbidity is the most important cause. The dangers are adverse drug reactions, which not infrequently lead to emergency hospitalizations, drug interactions, undermedication and overmedication, as well as treatments that may not have been carried out despite a clear indication. The approach of geriatric assessment in addition to careful diagnosis of multimorbidity as well as explicit definition of the treatment goal (if necessary also with relatives) and keeping an ongoing medication history with desired and undesired effects serve to provide clarity and actively prevent medication-associated problems.
In Switzerland, more than 3000 active ingredients in a total of over 12,400 pharmaceutical preparations are approved by Swissmedic. This number makes it impossible for a prescriber to know all the products. At the same time, treatment intensity and the number of physicians per patient are increasing. This constellation, together with the aging of the population, creates many new and potentially dangerous situations.
How is polypharmacy defined and how big is the problem?
Polypharmacy usually refers to the simultaneous use of five or more drugs or medications. Taking one or more medications that are not indicated. The definition is not evidence-based, but expresses the consensus opinion of various authors researching in this field [1].
We know that the phenomenon of polypharmacy is common, with 57% of ≥65-year-old U.S. women taking at least five medications simultaneously, and 12% taking at least 10 medications. The number of “over-the-counter” medications taken in the United States among 74-year-olds is at least one in 90% and at least two to four in 59% [2].
51% of a cohort of 72-year-old Europeans were taking at least six medications simultaneously. The same study mentions that, in addition, 50-60% of elderly patients take at least one medication without indication, 30% take at least one ineffective medication, and 16% take two medications for the same indication. In contrast, 64% have a clear treatment indication for which they do not receive any medication [2]. Considering the potential consequences of incorrect medication, these numbers are worrisome.
The most important risk factors for polypharmacy
Multimorbidity is the main risk factor for polymedication. In Scotland, 65-84 year olds were found to have an average of 2.6 diseases – only about one-third of those studied at this age were not multimorbid. Approximately 20% had five or more relevant diseases. Among those aged ≥85 years, the corresponding figures were as high as 3.26%, 18.5%, and 30%. The disease combinations were found to be sufficiently known from everyday clinical practice: Patients with COPD additionally suffered from coronary heart disease, diabetes mellitus, heart failure, stroke, atrial fibrillation, painful conditions, depression and anxiety disorders [3]. A high number of polymorbid patients were also found among inpatients in internal medicine at the University Hospital Zurich [4].
Thus, age is the most important risk factor for polypharmacy. The number of physician consultations and the number of physicians involved in a treatment are further risk factors.
Unconditional implementation of treatment guidelines can lead to dangerous polypharmacy. Guidelines (e.g. for hypertension treatment, heart failure, atrial fibrillation, hyperlipidemia, etc.) are usually very differentiated. Therefore, the practitioner has to account for exactly which group the patient currently being treated really belongs to. Patient age, weight, possibly gender, kidney and liver function, polymorbidity, and concomitant medications play the greatest role [5].
For geriatric patients, always clarify the intention to treat based on the goal of treatment. The older the patient, the less significant becomes the treatment of asymptomatic risk factors such as hyperlipidemia, hypertension (less low thresholds), and diabetes mellitus (higher HbA1c tolerance). This is important to avoid problems such as orthostasis (in the case of BP treatment) or hypoglycemia (in the case of diabetes treatment). For this, the treatment of symptoms such as pain, constipation, tremor, dizziness, etc. becomes more important. Symptomatic adverse drug reactions are to be avoided.
The main risks and consequences of polypharmacy
In general, it can be said that as the number of medications a patient takes increases, so does the risk of adverse drug reactions (ADRs). An American study over 32 years showed that the rate of hospital-onset serious and fatal UAW was 2.29%. The UAW of the same severity that resulted in hospitalization had a rate of 4.83% [6].
In 1999, an adverse drug reaction was found in 6.4% of patients at the Ospedale San Giovanni in Bellinzona. 96% of these ADRs were predictable, 73% were serious, and 57% of medications were unnecessary or incorrectly prescribed. In two-thirds, the UAW had led to hospitalizations [7]. The numbers prove that we are dealing with common and often preventable problems.
In order to reduce polypharmacy and its negative consequences, in 1992 Hanlon et al. the later extended “medication appropriateness index” was published. Table 1 contains the extended MAI index with 14 key questions [1]. The MAI questions simultaneously define the main risks of polypharmacy.
Dangerous drugs
Various lists of potentially dangerous drugs exist for patients aged 65 years or older: Beers list (USA 1997), PRISCUS list (D 2010) [8], FORTA list (D 2013) [9]. These all have the disadvantage that they quickly become obsolete, are never comprehensive, or are not available at all. are complete and do not take into account regional differences in available medications. Their use in clinical practice also fails due to the availability of the information at the time of prescription. No one is able to have these lists, totaling over 100 medications, present in their memory. However, one can make an effort not to include the listed drugs in one’s personal “prescription repertoire.”
In Ireland, Gallagher et al. published the STOPP and START criteria for patients over 65 years of age [10]. The former describe 65 clinically significant criteria for potentially inappropriate prescribing while the START criteria include 22 evidence-based prescribing indications for common conditions. Mentioned lists resp. these criteria could be used as the basis for an IT-based prescribing tool.
We know from a wide variety of studies that special caution and accuracy are indicated for the drugs listed in Table 2.
Dangerous situations
In addition to adverse drug reactions, dosage and prescription errors, interactions are particularly dangerous. The possibilities for interaction increase disproportionately as the number of drugs administered simultaneously increases. Five substances lead to ten pair formations, eight already to 28 and ten pharmaceuticals can even form 45 mutually influencing pairs. The general formula for this is I = (n2-n) : 2.
Influencing the effect of a vitamin K antagonist (e.g., phenprocoumon) by adding other pharmaceuticals can lead to underanticoagulation (risk of thromboembolism) or overanticoagulation (risk of bleeding).
For major interactions with vitamin K antagonists and direct oral anticoagulants (DOAKs), see Table 3.
Amiodarone, unlike dronedarone, is not problematic with DOAK. It should be noted that the anticoagulant effect of DOAKs cannot be measured in routine daily practice – in contrast to the INR value (Quick) for VKAs. For further interaction data, we refer to the clear compilation in Hafner 2010 [11].
What can be done in dealing with polypharmacy?
Clarifying the patient’s situation as precisely as possible creates a good starting point: determining functional impairments with the help of a geriatric assessment is helpful. Next, clarity about comorbidities must be obtained. Therapy goals should be set together with the patient or family members. From this follows which morbidities, if any, are not (or no longer) treated – this taking into account the risks with and without therapy. After that, the therapies can be selected and coordinated, e.g. by means of MAI questions. This is followed by the interaction test. In the end, the feasibility and implementability of the ordinance must be reviewed once again. Only then is prescribed with associated instructions to patient and environment (caregivers).
Possibly, certain medications can be replaced by other prescriptions (behavioral, physical, nursing measures).
Geriatrician A. E. Stuck recently published a possible algorithm for prescriptions in aged patients in Swiss Medical Forum [12]. It seems important to us that firstly the problem is realized at all and secondly that each prescriber chooses a standardized procedure that minimizes polypharmacy and – if it is necessary – keeps its risks as small as possible.
Important points for practice
- Capture the patient with their main and co-morbidities and fragility with the main geriatric problems using assessment.
- Formulate treatment goals; symptomatic vs. evidence-based therapies; critique existing therapies for risk reduction.
- Apply MAI questions (best implementable using informatics/electronic ordinance).
- Record interactions, contraindications (STOPP questions, best implementable by informatics/electronic prescription).
- Potential missing medications (START questions, best implementable via informatics/electronic prescribing).
- therapy at the patient feasible at all?
- Formulate prescription with intake recommendation and possible assistance (relatives, Spitex, etc.).
- Record prescriptions continuously with effect, adverse effects or lack of effect.
Literature:
- Haefeli WE: Polypharmacy. Switzerland Med Forum 2011; 11(47): 847-852.
- Hajjar E, et al: Polypharmacy in Elderly Patients. Am J Geriatr Pharamcother 2007; 5: 345-351.
- Barnett K, et al: Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet 2012; 380: 37-43.
- Schneider F, et al: Prevalence of multimorbidity in medical inpatients. Swiss Med Wkly 2012; 142: w13533.
- Mancia G, et al: ESH/ESC Guidelines for the management of arterial hypertension. European Heart Journal 2013; 34: 2159-2219.
- Lazarou J: Incidence of Adverse Drug Reactions in Hospitalised Patients. Jama 1998; 279: 1200-1205.
- Lepori V: Adverse internal medicine drug reactions at hospital admission. Schweiz Med Wochenschr 1999; 129: 915-922.
- Holt S: Potentially inappropriate medication for the elderly: The PRISCUS list. Deutsches Ärzteblatt 2010; 107(31-32): 543-551.
- Kuhn-Thiel A: 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: 131-140.
- Gallagher P: STOPP (Screening Tool of Older Person’s Prescriptions) and START (Screening Tool to Alert physicians to Right Treatment). Consensus validation. International Journal of Clinical Pharmacology and Therapeutics 2008; 46: 72-83.
- Hafner V: Drug interactions. Internist 2010; 51: 359-370.
- Stuck AE, et al: Need for reform: a higher dose of geriatrics is needed. Swiss Medical Forum 2015; 15(1-2): 15-17.
HAUSARZT PRAXIS 2015; 10(6): 32-36
