Polypharmacy (Part I): a bigger problem than we think?

Polypharmacy is often associated with negative outcomes. According to a recent study, hospitalisation rates due to side effects have more than doubled.

Prevalence of hospitalisations and deaths due to ADRs is higher than previously reported

New data from 2022 confirms that adverse drug reactions (ADRs) are a significant contributor to unnecessary hospital admissions: an analysis of all hospitalisations (for at least 24 hours) in a month from a UK maximum care hospital found that almost one in five hospitalised patients (18.4%) experienced adverse drug reactions.5 ADRs were the main or contributory cause of 16.5% of admissions, with an estimated cost of $2.45 billion per year. This rate is more than double that of a 2004 study in the same region (6.5%).6 On average, patients with adverse drug reactions took significantly more medication and had more comorbidities.

The most frequently involved drugs currently include diuretics, inhaled corticosteroids (ICS), anticoagulants, proton pump inhibitors (PPI), platelet aggregation inhibitors, chemotherapeutic agents, antihypertensives, opiates and antidepressants/antipsychotics. 39.4% of side effects were categorised as (potentially) preventable. The mortality rate due to an adverse drug reaction was 0.34%.

Often overprescribed for respiratory diseases: Antibiotics and ICS

A recent survey of GPs and pulmonologists from six countries also showed a discrepancy between "best practice" and reality. Inhaled corticosteroids (ICS) were over-prescribed in primary care and GPs were less confident than pulmonologists in stopping them.7 This signal has been documented by several new studies. In one study that looked for both over- and under-therapy, over-prescription of ICS in outpatients with stable COPD was the most common deviation from guideline-compliant therapy overall (17.8%).8 It has been shown that ICS withdrawal is not associated with COPD exacerbations or COPD-related hospitalisations when done correctly.9

Although the overuse of antibiotics is discussed more frequently, it is usually in the context of the development of resistance and less in relation to the resulting damage and side effects. However, these are also significant, as a study published in the Journal of Internal Medicine emphasises.10,11 Antibiotics are prescribed unnecessarily in 50% of acute upper respiratory tract infections (aURIs), which according to current data corresponds to 34 million avoidable antibiotic prescriptions per year in the USA alone.

An analysis of 51 million patient encounters for aURIs over 15 years found that some of the riskiest antibiotics were rarely indicated and frequently used, resulting in severe side effects, sometimes requiring hospitalisation, in one in 300 patients.

The study authors emphasise that the likelihood of adverse events is likely to be much higher, as their analysis was only able to capture cases that were severe enough to result in follow-up visits to GP surgeries or clinics where the adverse event was coded as such. Previous estimates based on patient-reported adverse events of all severities give much higher NNH (Number Needed to Harm) values, between 8 and 10.

Conclusion: How can we protect older people in particular?

We can conclude with a proposal from Dr. Mosshammer's article mentioned at the beginning1: "Guideline-orientated treatments can lead to polypharmacy, i.e. the simultaneous long-term use of several medications". In concrete terms, prescribing cascades can also lead to polypharmacy if side effects are treated as symptoms.

Polypharmacy affects older people in particular. Due to ageing processes, this population is unfortunately affected by a higher rate of side effects anyway.2

You can access part II of this analysis here.

Sources
  1. [In English] Mosshammer, D. Polypharmacy—an Upward Trend with Unpredictable Effects (23.09.2016). Deutsches Ärzteblatt https://www.aerzteblatt.de/int/archive/article?id=182230.
  2. [In German] Priscus 2.0. https://www.priscus2-0.de/
  3. Thiem, U. et al. Reduction of potentially inappropriate medication in the elderly: design of a cluster-randomised controlled trial in German primary care practices (RIME). Ther Adv Drug Saf 12, 2042098620918459 (2020).
  4. Endres, H. G. et al. 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 11, e0146811 (2016).
  5. Osanlou, R., Walker, L., Hughes, D. A., Burnside, G. & Pirmohamed, M. Adverse drug reactions, multimorbidity and polypharmacy: a prospective analysis of 1 month of medical admissions. BMJ Open 12, e055551 (2022).
  6. Pirmohamed, M. et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 329, 15–19 (2004).
  7. Kocks, J. et al. Investigating the rationale for COPD maintenance therapy prescription across Europe, findings from a multi-country study. NPJ Prim Care Respir Med 33, 18 (2023).
  8. Rajnoveanu, R.-M. et al. Pulmonologists Adherence to the Chronic Obstructive Pulmonary Disease GOLD Guidelines: A Goal to Improve. Medicina 56, 422 (2020).
  9. Patel, S., Dickinson, S., Morris, K., Ashdown, H. F. & Chalmers, J. D. A descriptive cohort study of withdrawal from inhaled corticosteroids in COPD patients. NPJ Prim Care Respir Med 32, 25 (2022).
  10. Carmichael, H., Asch, S. M. & Bendavid, E. Clostridium difficile and other adverse events from overprescribed antibiotics for acute upper respiratory infection. Journal of Internal Medicine 293, 470–480 (2023).
  11. Study finds excess harm from commonly overprescribed antibiotics for patients resulting in widespread side effects. ScienceDaily https://www.sciencedaily.com/releases/2023/03/230330172137.htm.