Presenter

Matthew V. Rudorfer, M.D. 
Division of Services and Intervention Research 

Goal

The goal of this concept is to encourage the development of evidence-based treatments for adult ADHD that utilize nonstimulant medications, psychosocial interventions, and device-based approaches, in situations where stimulant monotherapy is insufficiently effective, difficult to tolerate, or undesirable.

Rationale

Until recently, ADHD was considered a disorder of childhood and treatments for ADHD were exclusively focused on young people. It is now recognized that while the most visible signs of childhood ADHD, such as motor hyperactivity, diminish by high school age, other symptoms (e.g., difficulty with sustained attention, tendency to lose things, challenges with organization) can follow people into adulthood, impairing relationships, higher education, and work functioning. It is estimated that 4% of adults live with ADHD, compared with 11% in those younger than 18. Many of those with adult ADHD must deal with stigma; co-occurring conditions, including substance use disorders, are common.

Since the development of the amphetamines in the 1930s, stimulants have been the mainstay of ADHD treatment across the lifespan. As with all medications, stimulants do not work equally well for everyone. These controlled drugs, subject of late to sporadic shortages and with a risk of abuse, dependence, misuse, and diversion as well as agitation, insomnia, and other possible adverse effects, may require alternative or complementary approaches. For example, there are now nonstimulant medications that are FDA-approved for treatment of ADHD across the lifespan, while other medications and a device (trigeminal nerve stimulation) are FDA-indicated for young people only but could benefit from study in adults. Other medications that have similar mechanisms of action as stimulants (i.e., action on dopaminergic systems) may also be candidates for treatment. Psychosocial approaches, including individual and group cognitive-behavioral therapy, may also help control symptoms of adult ADHD.

Given that adult ADHD was recognized in the Diagnostic and Statistical Manual of Mental Disorders for the first time only a decade ago, it is not surprising that optimal treatment strategies are yet to be codified, validated, and ranked. This concept encourages research on approaches for individuals with adult ADHD who respond only partially or not at all to stimulant medication, or for whom stimulants are best avoided due to co-existing substance use problems or intolerance to specific effects or adverse effects. Combination treatment approaches may also be of value in augmenting partial response to a stimulant, or as a replacement strategy. Device-based treatments would be welcome subjects of controlled trials, with appropriate FDA consultation. 

Additionally, research aimed at understanding the natural trajectory of ADHD, including the risk factors for continuation of the disorder into adulthood, would help advance the field.

Presenter

Vasudev R. Rao, M.B.B.S. [M.D.], M.S. 
Division of AIDS Research

Goal

The purpose of this concept is to identify modifiable targets and mechanisms to alleviate clinically relevant central nervous system (CNS) complications and to develop comprehensive validated treatment strategies to improve outcomes in people with HIV. The key goal of the concept is to improve quality of life, reduce symptom severity, and maximize functional capacity in individuals with HIV experiencing adverse CNS outcomes.

Rationale

A significant proportion of individuals living with HIV experience clinically relevant symptomatic CNS complications, which impact their quality of life and functional capacity. Despite extensive research efforts, existing clinical trials that have primarily focused on reducing inflammation and intensifying antiretroviral therapy (ART) have not achieved the anticipated improvements in CNS outcomes. Multifactorial pathogenesis of CNS complications results in significant outcome heterogeneity, making it challenging to identify broadly applicable treatment strategies. This highlights a critical gap and underscores the urgent need for identifying modifiable therapeutic targets and mechanisms in people with HIV experiencing adverse CNS complications. The identification of such targets and mechanisms is essential for the design of novel, effective treatment strategies. By leveraging clinical data-based decision trees, it is feasible to identify patient groups with modifiable targets (treatable traits) that can be precisely engaged through proven targeted interventions. This approach not only ensures a more personalized treatment strategy but also increases the likelihood of achieving meaningful clinical outcomes.

Furthermore, this concept encourages adopting milestone-based go/no-go approaches in treatment strategy design, coupled with iterative testing to validate target engagement and its correlation with observable changes in clinical outcomes ensuring that only promising interventions are advanced through the trial phases. This concept extends NIMH’s experimental therapeutics paradigm to foster development of personalized treatment strategies involving identifying and targeting specific, modifiable factors (treatable traits) contributing to CNS pathogenesis in people with HIV, ultimately improving the brain health outcomes in people with HIV. In conclusion, addressing the multifactorial nature of CNS complications in people with HIV requires a paradigm shift towards identifying patient groups with specific modifiable factors using clinical data-driven methodologies and structured milestone-based trial design. 

July 2, 2024
• Research Highlight

Mental health care after trauma is critical, especially for people in racial and ethnic minority groups who are at higher risk for developing post-traumatic stress disorder (PTSD). PTSD can be impairing, leading to stress or fear in everyday situations that harms a person’s health and well-being. Finding effective PTSD care is challenging in general, but systemic disparities and limited access make it even harder for people from racial and ethnic minority groups.

A new study funded by the National Institute of Mental Health marks a step toward reducing disparities in mental health care. It found that a collaborative care intervention delivered in real-world settings significantly reduced PTSD symptoms among patients from racial and ethnic minority backgrounds.

How did the researchers treat PTSD symptoms?

Collaborative care  is a team-based, patient-centered approach to treating mental disorders in acute and primary care settings. Health care providers work as a team and with the patient to provide comprehensive care tailored to the patient’s needs and preferences. In a “stepped” method, providers systematically and flexibly adjust the level of care based on the patient’s condition and response to treatment.

While previous studies  have shown that collaborative care can reduce PTSD symptoms, few studies have examined its ability to address the unique mental health needs and disparities experienced by racial and ethnic minority groups. This study, which had support from the NIH Common Fund’s Health Care Systems Research Collaboratory , is one of the first multisite studies to compare collaborative care among White and non-White trauma patients.

What did the researchers do in this study?

Douglas Zatzick, M.D. , senior investigator on the project, and Khadija Abu, B.A., lead author on the paper, collaborated with colleagues at the University of Washington School of Medicine’s Harborview Trauma Center. They analyzed data from a large clinical trial of stepped collaborative care conducted at 25 trauma centers across the United States.

People who were 18 years and older, seeking care for an injury, and experiencing a high level of distress based on a validated PTSD measure were eligible to participate. All participants self-reported their race and ethnicity. More than half (350 patients) identified as Hispanic or non-White (Asian, American Indian, Black, Native Hawaiian or Alaskan, Pacific Islander, or another race), including those endorsing more than one race. The other 285 patients identified as non-Hispanic White.

Patients were randomized to receive either enhanced usual care or stepped collaborative care.

• Enhanced usual care: Patients received care as usual at the trauma center, which included PTSD screenings, a baseline evaluation, and follow-up interviews. The enhanced aspect was that nurses were notified if a patient’s PTSD score was above a specified threshold.
• Stepped collaborative care: The intervention consisted of enhanced usual care plus additional follow-up, including proactive care management, cognitive behavioral therapy, and medication. Care was tailored to each patient’s specific postinjury needs and treatment preferences. Patients who showed ongoing PTSD symptoms received stepped-up care in the form of medication adjustments, additional therapy, or both.

Patients rated their PTSD symptoms at intake and 3, 6, and 12 months after their injury. They also completed measures of depression symptoms, alcohol use problems, and physical function at intake and at the three post-injury time points. For each racial and ethnic group, analyses compared scores between patients who received enhanced usual care versus the stepped collaborative care intervention.

What did the researchers find in the study?

Six months after their injury, Hispanic or non-White patients who received collaborative care reported significantly lower PTSD symptoms compared to those who received usual care (with no difference at 3- or 12-months post-injury). The researchers note that most post-injury care occurred within the first 6 months, possibly contributing to a lack of significant effects at 3 months and a drop off of effects at 12 months.

In contrast, no significant group difference was found for non-Hispanic White patients. Those who received usual care or collaborative care showed a similar change in PTSD symptoms at all time points, indicating that the intervention was no more effective than usual care for White patents in this study.

There was no change in self-reported depression symptoms, alcohol use problems, or physical function for either group, regardless of whether they received usual care or collaborative care. This suggests that the intervention specifically helps with PTSD but not with other common trauma-related symptoms.

What do the findings mean?

Findings from this large, randomized clinical trial support comprehensive care delivered by clinicians as effective for treating mental disorders, including PTSD. The study also suggests that this comprehensive form of care is beneficial for people from racial and ethnic minority backgrounds, who often face disparities in medical settings. Among the factors the researchers attribute to the intervention’s success for a diverse group of trauma survivors are its patient-centered focus, flexible nature tailored to individual needs, and emphasis on shared decision-making.

This study is already having a real-world impact by informing trauma care guidelines in the United States. The researchers’ longstanding work with this population has helped establish best practices for screening and treating mental health and substance use disorders among trauma survivors. Based on the results of this study, trauma centers are now implementing a screening and referral process for patients at high risk for mental disorders after injury as part of a new standard of care. The next step for the researchers is to test this new standard of care against the collaborative care intervention .

This study was limited by collapsing racial and ethnic groups into two categories, possibly masking differences in treatment responses. Replicating the study with larger samples would allow for more nuanced comparisons to see for which groups the intervention works best. Additionally, many patients in the study had experienced prior traumatic events and been hospitalized for PTSD, which may have led to different results compared to other collaborative care studies. Researchers should continue to explore collaborative care with diverse patient groups across different health care settings and with other mental disorders to refine the intervention and help make mental health care more equitable and effective.

Reference

Abu, K., Bedard-Gilligan, M., Moodliar, R., Bulger, E. M., Hernandez, A., Knutzen, T., Shoyer, J., Birk, N., Conde, C., Engstrom, A., Ryan, P., Wang, J., Russo, J., & Zatzick, D. F. (2024). Can stepped collaborative care interventions improve post-traumatic stress disorder symptoms for racial and ethnic minority injury survivors? Trauma Surgery & Acute Care Open, 9, Article e001232. https://doi.org/10.1136/tsaco-2023-001232 

Grants

MH130460 , MH106338 , AT009676 

Clinical trial

NCT02655354