Sequential Trial of Adding Buprenorphine, Cognitive Behavioral Treatment, and Transcranial Magnetic Stimulation to Improve Outcomes of Long-Term Opioid Therapy for Chronic Pain (ACTION)

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ABSTRACT A significant proportion of patients on Long Term Opioid Therapy (LTOT) have suboptimal pain relief and/or poor functioning despite significant risks. Because LTOT tapering can cause disabling withdrawal symptoms, the decision to taper or transition from LTOT can be daunting and create a clinical dilemma. Novel and effective treatment approaches that improve pain and quality of life (QOL) for individuals on LTOT while reducing risk are needed, but it is essential to ensure these initiatives are patient-centered. Offering treatment trials that can be “added to” current LTOT management without having to prospectively commit to an opioid taper or experience opioid withdrawal could significantly enhance the rates of safe, patient-centered, and effective LTOT risk reduction while improving pain and QOL. The proposed study addresses this critical need by sequentially evaluating trials of three evidence-based treatments for chronic pain that can be “added to” LTOT without having to experience opioid withdrawal or commit to a taper. In this study, individuals on LTOT will first trial a 7-day initiation of low-dose transdermal buprenorphine to determine safety and tolerability, and then will enter a blinded randomized discontinuation trial to evaluate efficacy of transdermal buprenorphine on pain severity among those on LTOT. Those who respond positively to the buprenorphine trial and want to transition to buprenorphine (and off LTOT) will be transitioned and followed as a prospective cohort. Those who do not respond to buprenorphine will undergo a second randomization evaluating the effectiveness of a Brief Cognitive Behavioral Intervention (CBI) for Pain combined with a 3-day “accelerated” course of Brain Stimulation (repetitive Transcranial Stimulation; rTMS) on pain severity. The proposed study aims to improve engagement of individuals on LTOT to make informed treatment decisions about LTOT; provide much needed safety and tolerability data on low-dose buprenorphine induction strategies; and evaluate the effectiveness of a novel combined non-pharmacological treatment that can address pain, opioid risk, and depression among those who do not respond to buprenorphine transition. Key innovations include the use of low-commitment, patient-centered ”trials” of treatment without mandating withdrawal and the evaluation of shorter “accelerated” protocols of brain stimulation that can enhance CBI that make this novel intervention scalable, generalizable and sustainable. This application is directly responsive to the FOA (RFA-DA-23-041), which underscores the importance of engaging individuals with lived experience to inform multilevel interventions aimed at improving quality of life and reducing harm for those on LTOT. It is also consistent with the research priorities of the HEAL initiative to optimize care for individuals with chronic pain and those at risk for opioid-related harms. The findings from this study will provide novel and critically needed empirical evidence to inform clinical practice and advance the science in this area.