Etherton-Beer C, Page A, Naganathan V, Potter K, Comans T, Hilmer SN, McLachlan AJ, Lindley RI, Mangin D. Deprescribing to optimise health outcomes for frail older people: a double-blind placebo-controlled randomised controlled trial-outcomes of the Opti-med study. Age Ageing. 2023 May 1;52(5):afad081. doi: 10.1093/ageing/afad081. PMID: 37247404; PMCID: PMC10226731.
The Opti-med study, conducted between 2014 and 2018, was a double-blind, randomized, placebo-controlled trial conducted across Sydney and Perth. The study’s primary objective was to investigate the effects of deprescribing multiple medications in the target population of older individuals residing in residential aged care facilities (RACFs). The study aimed to assess the impact of deprescribing on survival, quality of life, and clinical outcomes within this population while focusing on reducing medication burden and optimizing medication use.
The authors conducted the study with three groups: blinded control, blinded intervention, and open intervention. The intervention in this study involved a structured process of medication review, which aimed to identify potential targets for deprescribing among the participants by thoroughly reviewing their regular oral medications and PRN (as needed) medicines. This process followed established criteria and guidelines. The researchers obtained assent from the participants’ general practitioners (GPs). In the blinded groups, the medications targeted for deprescribing were encapsulated to maintain blinding and avoid placebo/nocebo effects. The blind intervention group underwent medication withdrawal based on the developed plans, while the blind control group continued their usual medication use with placebo encapsulation to maintain blinding. The study also included an open intervention group where deprescribing was conducted without blinding. Throughout the implementation phase, monitoring for adverse events occurred, and any necessary adjustments were made in consultation with the GPs.
The study enrolled 303 participants aged 65 and older residing in the RACFs, with the majority (76%) being female, with a mean age of 85.0±7.5 years. On average, participants in the blind intervention group had 2.7 medications deprescribed by 12 months, compared to 2.3 deprescribed medications in the open intervention group and 0.2 in the control group. This reduction in medication use did not seem to negatively impact their clinical outcomes. Notably, deprescribing regular medicines was not associated with a significant increase in the number of ‘when required’ medicines administered. Furthermore, there were no significant differences in mortality between the three groups: compared with the blinded control group, the hazard ratio for mortality (HR) in the blinded intervention group was 0.93, 95% CI 0.50, 1.73, P = 0.83), and the HR in the open intervention group was 1.47 (95% CI 0.83, 2.61, P = 0.19). However, the study faced challenges in recruiting participants, reaching only about one-third of the intended number. This limited the statistical power to measure outcomes such as mortality and hospitalization. The authors suggested that factors like the complexity of the interventions and potential medication changes may have raised concerns among potential participants. Additionally, the study design, which involved coordination and agreement from multiple stakeholders, including residential aged care facilities, individual residents, general practitioners, and pharmacies, could have presented logistical challenges and affected participation rates.
Primary author Christopher Etherton-Beer reflects on the potential implications or recommendations for future research based on their findings, especially regarding the undetermined impact of deprescribing on survival:
“We hoped to power the study for mortality (as it is a “hard” clinical endpoint). Although this wasn’t possible, we feel that the results of our study (including both blinded and open arms) are reassuring with respect to the safety of deprescribing. In terms of further research we have published cross sectional and process evaluation data from Opti-Med here and here. We are currently working on the pre-specified economic analysis of Opti-Med and hope to have this in press shortly. More broadly our ongoing work is focusing on a range of implementation studies. We feel that the blinded data are really valuable and that there is a need for further, high quality, randomised data evaluating deprescribing interventions in a range of clinical contexts.”
Authored by Caroline Eskandar