Objective: Despite the heightened urgency of the current prescription opioid crisis, few psychotherapies have been evaluated for chronic pain patients receiving long-term opioid analgesics. Current psychological pain treatments focus primarily on ameliorating negative affective processes, yet basic science suggests that risk for opioid misuse is linked with a dearth of positive affect. Interventions that modulate positive psychological processes may produce therapeutic benefits among patients with opioid-treated chronic pain. The aim of this study was to conduct a theory-driven mechanistic analysis of proximal outcome data from a Stage 2 randomized controlled trial of Mindfulness-Oriented Recovery Enhancement (MORE), an integrative intervention designed to promote positive psychological health. Method: Patients with opioid-treated chronic pain (N = 95; age = 56.8 ± 11.7; 66% female) were randomized to 8 weeks of therapist-led MORE or support group (SG) interventions. A latent positive psychological health variable comprised of positive affect, meaning in life, and self-transcendence measures was examined as a mediator of the effect of MORE on changes in pain severity at posttreatment and opioid misuse risk by 3-month follow-up. Results: Participants in MORE reported significantly greater reductions in pain severity by posttreatment (p = .03) and opioid misuse risk by 3-month follow-up (p = .03) and significantly greater increases in positive psychological health (p < .001) than SG participants. Increases in positive psychological health mediated the effect of MORE on pain severity by posttreatment (p = .048), which in turn predicted decreases in opioid misuse risk by follow-up (p = .02). Conclusions: Targeting positive psychological mechanisms via MORE and other psychological interventions may reduce opioid misuse risk among chronic pain patients receiving long-term opioid therapy.

Trial Registry: ClinicalTrials.gov ; registration ID number: NCT02590029 URL: https://clinicaltrials.gov/ct2/show/NCT02590029.

Mindfulness-based interventions have been heralded as promising means of alleviating chronic stress. While meta-analyses indicate that mindfulness-based interventions significantly reduce global measures of stress, how mindfulness-based interventions modulate the specific mechanisms underpinning chronic stress as operationalized by the National Institute of Mental Health research domain criteria (RDoC) of sustained threat has not yet been detailed in the literature. To address this knowledge gap, this article aims to (1) review evidence that mindfulness-based interventions ameliorate each of the 10 elements of behavioral dysregulation characterizing sustained threat via an array of mindful counter-regulatory strategies; (2) review evidence that mindfulness-based interventions modify biological domains implicated in sustained threat, such as the hypothalamic–pituitary–adrenal axis, as well as brain circuits involved in attentional function, limbic reactivity, habit behavior, and the default mode network; and (3) integrate these findings into a novel conceptual framework of mindful self-regulation in the face of stress—the Mindfulness-to-Meaning Theory. Taken together, the extant body of scientific evidence suggests that the practice of mindfulness enhances a range biobehavioral factors implicated in adaptive stress coping and induces self-referential plasticity, leading to the ability to find meaning in adversity. These mechanistic findings can inform the treatment development process to optimize the next generation of mindfulness-based interventions for greater therapeutic efficacy.

IMPORTANCE Successful treatment of opioid misuse among people with chronic pain has proven elusive. Guidelines recommend nonopioid therapies, but the efficacy of mindfulness-based interventions for opioid misuse is uncertain.OBJECTIVE To evaluate the efficacy of Mindfulness-Oriented Recovery Enhancement (MORE) for the reduction of opioid misuse and chronic pain. DESIGN, SETTING, AND PARTICIPANTSThis interviewer-blinded randomized clinical trial enrolled patients from primary care clinics in Utah between January 4, 2016, and January 16, 2020. The study included 250 adults with chronic pain receiving long-term opioid therapy who were misusing opioid medications. INTERVENTIONS Treatment with MORE (comprising training in mindfulness, reappraisal, and savoring positive experiences) or supportive group psychotherapy (control condition) across 8 weekly 2-hour group sessions.MAIN OUTCOMES AND MEASURES Primary outcomes were (1) opioid misuse assessed by the Drug Misuse Index (self-report, interview, and urine screen) and ( 2) pain severity and pain-related functional interference, assessed by subscale scores on the Brief Pain Inventory through 9 months of follow-up. Secondary outcomes were opioid dose, emotional distress, and ecological momentary assessments of opioid craving. The minimum intervention dose was defined as 4 or more completed sessions of MORE or supportive group psychotherapy. RESULTS Among 250 participants (159 women [63.6%]; mean [SD] age, 51.8 [11.9] years), 129 were randomized to the MORE group and 121 to the supportive psychotherapy group. Overall, 17 participants (6.8%) were Hispanic or Latino, 218 (87.2%) were White, and 15 (6.0%) were of other races and/or ethnicities (2 American Indian, 3 Asian, 1 Black, 2 Pacific Islander, and 7 did not specify). Atbaseline,themeandurationofpainwas14.7years(range,1-60years),andthemean(SD)morphineequivalent opioid dose was 101.0 (266.3) mg (IQR, 16.0-90.0 mg). A total of 203 participants (81.2%) received the minimum intervention dose (mean [SD], 5.7 [2.2] sessions); at 9 months, 92 of 250 participants (36.8%) discontinued the study. The overall odds ratio for reduction in opioid misuse through the 9-month follow-up period in the MORE group compared with the supportive psychotherapygroupwas2.06(95%CI,1.17-3.61;P = .01).At9months,36of80participants(45.0%) in the MORE group were no longer misusing opioids compared with 19 of 78 participants (24.4%) in the supportive psychotherapy group. Mixed models demonstrated that MORE was superior to supportive psychotherapy through 9 months of follow-up for pain severity (between-group effect: 0.49; 95% CI, 0.17-0.81; P = .003) and pain-related functional interference (between-group effect: 1.07; 95% CI, 0.64-1.50; P < .001). Participants in the MORE group reduced their opioid dose to a greater extent than those in the supportive psychotherapy group. The MORE group also had lower emotional distress and opioid craving. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, among adult participants in a primary care setting, t...

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