Abstract/Project Summary – PROJECT 2 Depression and anxiety are under-recognized and undertreated in older adults with cancer. More than a million older adults will be diagnosed with cancer this year. Each of these individuals are at greater risk for depression/anxiety than the general older population. The perioperative period is a particularly vulnerable time, as the patient is concurrently confronted with a life-changing diagnosis as well as functional and physical changes that accompany a major surgery. Most older adults with both cancer and depression/anxiety do not receive appropriate mental health treatment, and if they do, it is typically pharmacologic treatment only, further exacerbating already rampant polypharmacy. In this proposal, we will optimize and test a tailored pharmacological and behavioral intervention bundle for older patients undergoing surgery for cancer, with clinically significant depressive and anxiety symptoms. We will institute a perioperative mental healthcare intervention bundle including: (1) applying a proven behavioral intervention, behavioral activation (BA), with strategies based on patient preferences and needs; and (2) medication optimization and deprescribing (MOD), targeting to optimize dosages of anti-depressant medications, and stopping harmful or ineffective medications. Aim 1 (Adaptation): Informed by a collaborative planning approach, we will adapt, develop and implement an optimal perioperative mental health intervention bundle for older adults undergoing planned cancer surgery. Through stakeholder input, we will develop and iteratively adapt a behavioral and medication optimization intervention bundle for implementation in this population. Following initial protocol development, through treatment development trials, we will iteratively optimize the intervention through interactive feedback from patients over the age of 65 undergoing major surgery for cancer, and other stakeholders, noting barriers and facilitators to program completion. Aim 2 (Testing): Using a hybrid Type 1 randomized controlled trial design, we will compare the effectiveness of the intervention bundle with usual care in reducing symptoms of depression and anxiety in older patients with cancer undergoing oncologic surgery. For this aim, 100 patients with symptoms of depression and anxiety will be randomly assigned to the pharmacological and behavioral intervention bundle or usual care. Pre-operative depression and anxiety are associated with a host of adverse outcomes after surgery, including medical complications, falls, delirium, and mortality. Thus, medication optimization and deprescribing, in an intervention bundle with behavioral activation treatment of depression and anxiety in older adults with cancer, is expected to improve not only symptoms of depression and anxiety but also other important post-operative outcomes.