Funded Projects

Due to the opioid misuse epidemic across the nation, more infants are being exposed to narcotics during fetal life and developing neonatal opioid withdrawal syndrome (NOWS) in the neonatal period. Critical gaps remain in our knowledge with respect to best practices for identifying and managing infants with NOWS and no large-scale studies have been published on treatments undertaken and later outcomes of infants with NOWS. To address these gaps in knowledge, the Advancing Clinical Trials in Neonatal Opioid Withdrawal Syndrome (ACT NOW) study will evaluate treatment options and improve clinical care of infants with NAS/NOWS. This collaborative effort will conduct two trials: 1) Eating, Sleeping, Consoling for Neonatal Withdrawal (ESC-NOW): a Function-Based Assessment and Management Approach (ESC Study); and 2) Pragmatic, Randomized, Blinded Trial to Shorten Pharmacologic Treatment of Newborns With Neonatal Opioid Withdrawal Syndrome (NOWS) (Weaning Study).

Opioid overdose deaths disproportionately affect Black individuals in the United States. While the use of complementary and integrative pain treatments is effective and widely recommended, Black pain patients (especially those who also have depression) face barriers to the use of these approaches. This project will refine, test, and prepare to implement a novel approach to overcoming these treatment barriers. The research will partner with and empower Black patients to find safe, effective pain treatments that best match their values, preferences, and lifestyles.

As prescription opioid drug abuse and overdose-related deaths continue to skyrocket in the United States, the need for new and more effective non-addictive pain drugs to treat chronic pain remains critical. This research is conducting studies in animal models of a small molecule that has high potential to treat chronic pain conditions associated with neuropathy and/or inflammation. The goal of this project is to conduct dosing and other studies leading up to an animal model study of the potential drug in a toxicology study for 28 days. Results may lead to Investigative New Drug regulatory clearance to begin clinical studies to validate the potential drug’s efficacy and safety.

Mortality and morbidity related to suicidal behavior and opioid use disorder (OUD) have increased significantly over the past decade. These two public health crises are intertwined at multiple levels. Medications for OUD, especially buprenorphine, have been shown to decrease opioid use and reduce the multiple negative consequences of OUD, including fatal and nonfatal overdose, criminal justice involvement, infectious complications, and misuse of other substances. In addition, small randomized trials of buprenorphine treatment in treatment-resistant depression (with or without co-occurring OUD) suggest that buprenorphine reduces depressive symptoms and suicidal ideation. This large study will evaluate the effects of starting buprenorphine treatment on self-harm and suicide attempt among people with opioid use disorder, including those with and without co-occurring mental health conditions or other known risk factors for suicidal behavior. Comprehensive health records data from four large health systems serving a combined member/patient population of approximately 11 million will be examined for the overall effect of buprenorphine treatment on subsequent self-harm or suicide attempt, including differences in effects between patient subgroups and specificity of effects to buprenorphine vs other medications.

This study will evaluate the implementation of the Zero Suicide framework across six health systems serving over nine million people in collaboration with the Mental Health Research Network. The project will incorporate the voice of the patient and provider stakeholders as part of the implementation of the Zero Suicide framework in three health settings from the NIMH-funded parent award as well as the Southcentral Foundation which is an Alaska Native-owned, nonprofit health care organization serving nearly 65,000 American Indian/Alaskan Native people living in and around Anchorage, Alaska. The team will first systematically engage patients, providers, national consumer advocacy groups, and MHRN scientists in formulating research questions to address the prevention of opioid-related overdoses in people with Opioid Use Disorders (OUD) or people without diagnosed OUD who are using opioids for pain management. Next, the team will utilize semi-structured interviews to determine how people with OUD or people without diagnosed OUD who are using opioids for pain management are experiencing the implementation of the Zero Suicide framework in four diverse health systems. Experiences will be recorded using 80 semi-structured phone interviews in a diverse sample of patients who have survived an opioid-related overdose (50% intentional; 50% unintentional), as well as 20 Addiction Medicine, Primary Care, and/or Specialty Pain Medicine providers.

The parent U19, “Southwest Hub for American Indian Youth Suicide Prevention,” builds capacity among local tribal governments, investigators, interventionists, and service providers across three Southwestern states to: 1) identify at-risk youth and gather robust local data through surveillance; 2) provide regular monitoring and brief interventions to close gaps in continuity of care; and 3) convene regularly for shared learning, policy development, and dissemination of best practices. The parent U19 includes an innovative SMART trial study design. The purpose of this supplement is to gather data on opioid use. Our supplement aims are to: 1) expand suicide surveillance in the Southwest Hub to include opioid use as a potential precipitant, facilitator, and risk factor for subsequent suicidal behavior; 2) explore community beliefs about correlates of risk, protective factors, and behavior functions of opioid abuse in Native American youth; and 3) examine opioid use among SMART trial participants.

The project will address gaps in both risk identification and clinical management by utilizing comprehensive clinical data from a mature health information exchange containing more than 2.3 million patients across the spectrum of clinical care (hospitals, primary care, specialty care, community health centers, urgent care) to develop a statistically robust method to measure suicide risk associated with prescription opioid use. First, the team will couple data fusion techniques with machine learning-based approaches in identifying the clinical and demographic characteristics associated with elevated risk of suicidal behavior among prescription opioid users. Second, the team will develop clinical profiles of patients with higher risk of suicidal behavior associated with prescription opioids, and to incorporate these profiles in a clinical decision support platform that can be used for identification and intervention at the point of care. The clinical decision support tool developed under this proposal will provide a generalizable platform that could be extended to other more conventional opioid related outcomes such as OUD and overdose.

The project will apply natural language processing to a rich repository of suicide and other clinical electronic health record and vital statistics to detect opioid problem-related encounters in order to (1) explore the relation between suicide risk and opioid misuse and (2) test whether a Zero Suicide model?s intervention effect is moderated by opioid misuse and whether it can also help to reduce opioid-related harm. First, the team will extract opioid-related EHR data using a combination of diagnostic codes and natural language processing, validated by structured manual chart review using a standardized procedure. Next, they will analyze the interplay between suicide risk and opioid problems in encounters and patients within the repository. Third, they will assess the effect of Zero Suicide implementation on prospective fatal and non-fatal suicidal behavior in patients with an opioid problem and examine whether the implementation had an effect on the incidence of opioid-related outcomes, including intentional overdose.

Some medications for opioid use disorder (MOUD) can be provided in primary care (PC). Systems of team-based PC show promise for improving access and retention in OUD treatment. One such model, collaborative care (CC), includes a care manager, supervised by experts, who help provide evidence-based high-quality OUD care. While CC improves outcomes of depression, other mental health and substance use (MH/SU) disorders and pain, it is unknown how to optimally integrate CC for OUD with other MH/SU disorders. This pragmatic trial tests whether our model of CC for OUD and comorbid conditions increases engagement in MOUD treatment and improves depression symptoms in PC patients with OUD and depression. Innovative pragmatic elements include inclusion of all eligible patients in participating PC clinics, random recruitment and consent, and measurement of main outcomes using only secondary data. These pragmatic elements avoid studying only motivated patients and avoid activating patients randomized to usual care.

American Native (AN) communities experience high rates of trauma that compromise the mental health of parents and caregivers that in turn increases their children?s risk for suicide and substance use during adolescence and young adulthood. Without intervention, this intergenerational cycle may repeat. The goal of this study is to understand opioid use, suicide, and the social network characteristics of Fort Peck Assiniboine and Sioux parents and caregivers to determine how the social network of parents/adult caregivers are related to both risk for and protection from suicide and opioid use. This supplement will examine the effectiveness of a community health worker delivered, culturally tailored prevention intervention called Wa?Kan Ye?Zah on caregiver and child behavioral and mental health outcomes and assess the benefits of culturally enhancing the intervention for caregivers? well-being.

The goal of this proposal is to launch an innovative, multi-modal neuroimaging program that will investigate the longitudinal trajectory of the neurodevelopment of irritability across the preschool period. Differentiating clinically salient irritability from developmentally normative temperamental variation has proven to be a difficult task. This is made even more challenging during the preschool period, when irritability has hit its normative peak and measuring neurodevelopment is impeded by methodological constraints. This research will (1) identify specific biomarkers underlying preschool vulnerability for psychopathology by examining neural maturation in executive function as a predictor for clinical outcome; and (2) examine how the parenting environment moderates this vulnerability, with the overarching objective of identifying aberrant irritable trajectories as the foundation for future brain-based behavioral intervention. Primary analyses will (1) probe underlying executive function as a predictor of clinical outcome; and (2) examine parent-child neural synchrony as a predictor of executive function maturation.

This study will refine and test a collaborative care model for patients with opioid use disorder (OUD) and major depression, post-traumatic stress disorder, or an anxiety disorder in primary care. The primary aims of the study are: (1) prototype and test elements of the research team’s collaborative care models; (2) conduct a randomized study of three collaborative care conditions to determine which is most effective in improving outcomes for people with OUD and mental health conditions: Augmented Usual Care, Collaborative Care, or Collaborative Care + Social Worker; (3) measure clinician and organizational-level factors associated with implementation to increase success; (4) conduct a cost evaluation of each collaborative care model; and (5) work with smaller and rural practices to develop and test effective strategies to manage OUD. Successful completion of this study will provide evidence regarding the elements of integrated collaborative care required to maximize outcomes for individuals with OUD and psychiatric disorders.