Have We Forgotten About Therapeutic Failure in Older Adults?

Background: Three types of adverse drug events have been identified in studies of medication-related harms among older adults: adverse drug reactions, adverse drug withdrawal events, and therapeutic failures (TFs).

Methods: In this narrative review of medical literature through June 2024, we summarize relevant articles and discuss evidence-based approaches and opportunities for future research to address TFs, as they are lesser recognized adverse drug events.

Results: Despite more than three decades elapsing since TF was first described in 1991, we identified only 16 studies in our review that evaluated TF in older adults. The median rate of TFs among these 16 studies was 7.4%, and most TFs were considered preventable. Common reasons for TF in this population included medication nonadherence and underprescribing of necessary medications. These studies share several limitations, including weak observational study designs and relatively small samples that may not generalize to all populations of older adults. Finally, only five studies utilized an implicit tool (the Therapeutic Failure Questionnaire) that has been shown to have good interrater reliability.

Conclusions: We acknowledge that clinicians should, and often do, attend first to deprescribing and reducing polypharmacy in managing adverse drug reactions among older adults. We must not forget, however, about TFs as an important and predominantly preventable source of harm among our older adult patients. TFs increase the length of hospital stays, promote disease persistence, reduce quality of life, and increase social costs of disease. We believe TFs remain a prevalent and important problem in older adults. More data are needed from up-to-date robust observational studies to further understand the impact of TFs on economic and humanistic outcomes in older adults.