gms | German Medical Science

Background: Although their potential adverse effects may outweigh therapeutic benefits, drugs with anticholinergic effects are frequently prescribed to elderly patients. Important adverse effects include confusion (and delirium), dry mouth, constipation, blurred vision and respiratory infections due to decreased secretions, as well as reduced cognitive performance and functionality [1]. It is especially problematic that general practitioners may attribute these symptoms to age- or disease-related deterioration. To facilitate appropriate prescribing, lists of potentially inappropriate medications (PIM) have been published in recent years. Of the 83 substances included in the PRISCUS (Germany-specific PIM) list, 23 substances (28%) have a strong anticholinergic effect [2]. However, international studies have identified numerous weakly to moderately anticholinergic medications that may cause considerable harm via cumulative ‘anticholinergic burden’ (ADB) when an individual’s medication regimen includes multiple drugs [3], [4], [5]. The main objective of this research was to examine the health consequences of anticholinergic drug prescriptions in elderly patients with multimorbidity and receiving polypharmacy. The focus thereby is on self-reported quality of life and functional status.

Materials and Methods: To calculate the cumulative anticholinergic drug burden, we combined information from international studies identified using a comprehensive literature search. The resulting weighted list (0-3 points/medication) consisted of 608 drugs, including those on the PRISCUS list. We analyzed patients in the PRIMUM-database, which contains 505 randomly selected, cognitively intact patients (Mini Mental Status Exam >26) that are above 60 years of age, and have at least 3 chronic diseases and 5 medications. Data on quality of life (EQ-5D), functionality (VES-13), falls and cognition (verbal fluency, semantic test) were collected at baseline, and after 6 and 9 months. To determine whether ADB was associated with impairments in quality of life and functionality, we used mixed linear regression modeling, adjusting for data structure (e.g. clustering) and potential confounders.

Results: 498 patients (mean age: 72) provided 1422 relevant observations. A mean of 8.8 medications (0.5 with anticholinergic activity) was prescribed per patient, resulting in a cumulative ADB of 0.8 points. We observed a total of 54 ADB-relevant substances in the PRIMUM population. The highest burden was caused by amitriptyline, doxepin, prednisolone, trospium and tramadol. While amitriptilyne and doxepin are included in PRISCUS, prednisolone was only captured by the preliminary PRISCUS list and trospium and tramadol are actually described as possible therapeutic alternatives to PIMs. The majority (56%) of the ADB was caused by substances that are not in PRISCUS. ADB correlated significantly with reduced quality of life (p<0.01), as well as an increase in vulnerability (p=0.01) and the number of falls (p=0.05). We observed no significant correlation with verbal fluency. Per ADB-score point, quality of life decreased by 2.9%, functionality decreased by 8.9%, and falls increased by 22.7%. Relevant ADB substances that are not included as PIMs on the PRISCUS list had a stronger impact per score point on quality of life, functionality and falls than those that were not.

Conclusion: Our results support previous findings suggesting that drug treatments with anticholinergic effects may impair the health of elderly multimorbid patients receiving polypharmacy. Furthermore, our findings suggest that the negative health consequences of drugs with weak and moderate anticholinergic activity may be underestimated. The observed effects are small and should be investigated using validated instruments. It should be noted that some frequently prescribed substances with anticholinergic effects are not included on the PRISCUS list, and may even be recommended as treatment alternatives to listed PIMs.