Comorbid depression is highly prevalent in Veterans with chronic pain and contributes to greater pain severity, functional impairment, and suicide risk relative to those with chronic pain alone. Despite the well- known association between chronic pain and depression, current treatments fall short of producing meaningful improvements in function and quality of life in this population. In this application, we propose to address this problem by a novel intervention that combines repetitive Transcranial Magnetic Stimulation (rTMS) and Acceptance and Commitment Therapy (ACT). ACT is an evidence-based psychosocial intervention that improves function in Veterans with chronic pain. However, similar to the broader literature, comorbid depression significantly limits the efficacy of ACT, which may be directly related to dysfunctional brain circuits that maintain depression. rTMS is a non-invasive brain stimulation intervention that is FDA-cleared for the treatment of depression. The most commonly targeted stimulation area is the left dorsolateral prefrontal cortex (DLFPC), a prefrontal brain region involved in cognitive control and emotion regulation. rTMS over the left DLPFC has also been used to reduce pain intensity in patients with chronic pain, as the DLPFC is implicated in the affective processing of painful stimuli. Importantly, while rTMS has been shown to reduce depression severity and pain intensity, it does not directly address function. Thus, the proposed research will integrate rTMS and ACT with the goal of maximizing functional improvement in Veterans with chronic pain and depression. The purpose of this application is to examine the feasibility of a future randomized efficacy trial. A total of 24 Veterans with chronic pain and depression will be randomized into DLPFC-rTMS + ACT or sham-rTMS + ACT conditions. Multiple metrics of feasibility will be assessed, including general interest in the study, willingness to participate, enrollment, retention, drop-out, number of adverse events, and participant blindness to condition, as well as ratings of credibility, expectation, and treatment satisfaction. We will also estimate the preliminary impact of DLPFC-rTMS + ACT and sham-rTMS + ACT on function as measured by reductions in pain interference (primary clinical outcome). The intent of preliminary analyses is to obtain an additional indicator for a future large-scale trial, not to verify group differences. Further, we will include two cognitive control tasks, the Emotion Distractor and Attention-to-Breath tasks, with concurrent EEG recording as a potential objective indicator of treatment response. The study team has previously demonstrated the association between depression severity and DLPFC activity on these tasks. In the proposed study, we will explore the associations between treatment-related change in DLPFC activity and treatment outcomes. Veterans with chronic pain and depression do not have access to effective treatments. To address this need, we seek to examine the feasibility of a novel approach by integrating a somatic and a psychosocial intervention. Our scientific premise is that rTMS over the left DLPFC will remediate hypofunction of prefrontal brain circuits that is necessary to maximize the impact of ACT on function in Veterans with chronic pain and depression. Findings from the proposed research have the potential of substantially increasing the physical and psychosocial functioning of Veterans with chronic pain and depression.

Veterans with comorbid chronic pain and depression are highly prevalent, have poor functional status and low quality of life, are at increased risk of suicide and lack access to effective treatments. To address this problem, the proposed research will examine the feasibility of a novel approach that integrates repetitive Transcranial Magnetic Stimulation and Acceptance and Commitment Therapy with the overall goal of maximizing functional improvement in Veterans with chronic pain and depression. This is an important first-step in preparation for a future randomized efficacy trial. We will also include two cognitive control tasks with concurrent electroencephalography to explore as a potential objective indicator of treatment response. This application addresses a critical need within the Veterans Health Administration and is closely aligned with the focus area of developing suicide prevention treatments that influence participation in life roles.