Background Polypharmacy is common among older people and found to be associated with a high risk of mortality. However, little is known about how specific medications impact older adults with polypharmacy. Thus, this study aimed to investigate associations between high-risk medications and all-cause and cause-specific mortality among older adults with polypharmacy.

Methods Data came from Wave 6 (2012/2013) of the English Longitudinal Study of Ageing, a nationally representative sample of people aged 50 and older. 1705 participants with polypharmacy, defined as taking five or more long-term medications a day for conditions or symptoms, were included. First, using agglomerative hierarchical clustering method participants were grouped according to the use of 14 high-risk medication categories. Five clusters of high-risk medications were identified. Next, the relationship between the five high-risk medications clusters and all-cause and cause-specific mortality (followed up to March 2018) was examined. All-cause mortality was assessed by Cox proportional hazards model and competing-risks regression was employed for cause-specific mortality.

Results Five high-risk medication clusters were identified: 1) RAAS inhibitors 2) mental drugs 3) CNS drugs 4) RAAS inhibitors and antithrombotics and 5) antithrombotics. The mental drugs cluster showed higher risks of all-cause (HR=1.55, 95%CI=1.05, 2.28) and CVD (SHR=2.11, 95%CI=1.10, 4.05) mortality than CNS drugs cluster over six years, while others showed no differences in mortality. The mental drugs cluster showed the highest prevalence of antidepressants (64.1%), benzodiazepines (10.4%), antipsychotics (2.4%), antimanics (0.7%), opioids (33.2%) and muscle relaxants (21.5%) amongst the five medication patterns. The findings suggest that older adults with polypharmacy who take mental drugs (primarily antidepressants), opioids and muscle relaxants are prone to increase the risk of all-cause and CVD mortality, compared with those who did not take these types of medications.

*Abbreviation: RAAS: renin-angiotensin-aldosterone system, CNS: central nervous system, CVD: cardiovascular disease.

Conclusion The use of mental drugs, opioids, and muscle relaxants was found to add on mortality risk to community-dwelling older people with polypharmacy in England. This study supports the view that addictive pain management medications should be included in structured medication reviews, but also suggests that the prescription of mental medications and muscle relaxants in older adults with polypharmacy may need more attention. The reinforcement of structured medication reviews would contribute to the early intervention in medication use and may help reduce the mortality risk of people with polypharmacy.