depression
Suicide Prevention Research in a Rapidly Changing World
Posted on by Joshua A. Gordon, M.D., Ph.D., National Institute of Mental Health
As I sit down to write this blog, the COVID-19 pandemic continues to have a widespread impact, and we’re all trying to figure out our “new normal.” For some, figuring out the new normal has been especially difficult, and that’s something for all of us to consider during September, which is National Suicide Prevention Awareness Month. It’s such an important time to share what we know about suicide prevention and consider how we can further this knowledge to those in need.
At NIH’s National Institute of Mental Health (NIMH), we’ve been asking ourselves: What have we learned about suicide risk and prevention during the pandemic? And how should our research evolve to reflect a rapidly changing world?
Addressing Disparities
Over the last few years, people have been concerned about the pandemic’s impact on suicide rates. So far, data suggest that the overall suicide rate in the U.S. has remained steady. But there is concerning evidence that the pandemic has disproportionately affected suicide risk in historically underserved communities.
For example, data suggest that people in minority racial and ethnic groups experienced greater increases in suicidal thoughts during the pandemic [1]. Additional data indicate that suicide rates may be rising among some young adult racial and ethnic minority groups [2].
Structural racism and other social and environmental factors are major drivers of mental health disparities, and NIMH continues to invest in research to understand how these social determinants of health influence suicide risk. This research includes investigations into the effects of long-term and daily discrimination.
To mitigate these effects, it is critical that we identify specific underlying mechanisms so that we can develop targeted interventions. To this end, NIMH is supporting research in underserved communities to identify suicide risk and the protective factors and effective strategies for reducing this risk (e.g., RFA-MH-22-140, RFA-MH-21-188, RFA-MH-21-187). There are important lessons to be learned that we can’t afford to miss.
Building Solid Foundations
The pandemic also underscored the urgent need to support youth mental health. Indeed, in December 2021, U.S. Surgeon General Dr. Vivek Murthy issued the Advisory on Protecting Youth Mental Health, calling attention to increasing rates of depression and suicidal behaviors among young people. Crucially, the advisory highlighted the need to “recognize that mental health is an essential part of overall health.”
At NIMH, we know that establishing a foundation for good mental health early on can support a person’s overall health and well-being over a lifetime. In light of this, we are investing in research to identify effective prevention efforts that can help set kids on positive mental health trajectories early in life.
Additionally, by re-analyzing research investments already made, we are looking to see whether these early prevention efforts have meaningful impacts on later suicide risk and mental health outcomes. These findings may help to improve a range of systems—such as schools, social services, and health care—to better support kids’ mental health needs.
Improving and Expanding Access
The pandemic has also shown us that telehealth can be an effective means of delivering and increasing access to mental health care. The NIMH has supported research examining telehealth as a tool for improving suicide prevention services, including the use of digital tools that can help extend provider reach and support individuals at risk for suicide.
At the same time, NIMH is investing in work to understand the most effective ways to help providers use evidence-based approaches to prevent suicide. This research helps inform federal partners and others about the best ways to support policies and practices that help prevent suicide deaths.
In July, the Substance Abuse and Mental Health Services Administration (SAMHSA) launched the 988 Suicide & Crisis Lifeline, a three-digit suicide prevention and mental health crisis number. This service builds on the existing National Suicide Prevention Lifeline, allowing anyone to call or text 988 to connect with trained counselors and mental health services. Research supported by NIMH helped build the case for such lifelines, and now we’re calling for research aimed at identifying the best ways to help people use this evolving crisis support system.
Looking Ahead
With these and many other efforts, we are hopeful that people who are at risk for suicidal thoughts and behaviors will be able to access the evidence-based support and services they need. This National Suicide Prevention Awareness Month, I’d like to issue a call to action: Help raise awareness by sharing resources on how to recognize the warning signs for suicide and how to get help. By working together, we can prevent suicide and save lives.
References:
[1] Racial and ethnic disparities in the prevalence of stress and worry, mental health conditions, and increased substance use among adults during the COVID-19 pandemic – United States, April and May 2020. McKnight-Eily LR, Okoro CA, Strine TW, Verlenden J, Hollis ND, Njai R, Mitchell EW, Board A, Puddy R, Thomas C. MMWR Morb Mortal Wkly Rep. 2021 Feb 5;70(5):162-166.
[2] One Year In: COVID-19 and Mental Health. National Institute of Mental Health Director’s Message. April 9, 2021.
Links:
988 Suicide & Crisis Lifeline (Substance Abuse and Mental Health Services Administration, Rockville, MD)
Substance Abuse and Mental Health Services Administration Treatment Locator (SAMHSA)
Help for Mental Illnesses (National Institute of Mental Health/NIH)
Suicide Prevention (NIMH)
Digital Shareables on Suicide Prevention (NIMH)
Digital Shareables on Coping with COVID-19 (NIMH)
NIMH Director’s Messages about COVID-19 (NIMH)
NIMH Director’s Messages about Suicide (NIMH)
Note: Dr. Lawrence Tabak, who performs the duties of the NIH Director, has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 16th in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.
Precision Deep Brain Stimulation Shows Initial Promise for Severe Depression
Posted on by Dr. Francis Collins
For many people struggling with depression, antidepressants and talk therapy can help to provide relief. But for some, the treatments don’t help nearly enough. I’m happy to share some early groundbreaking research in alleviating treatment-resistant depression in a whole new way: implanting a pacemaker-like device capable of delivering therapeutic electrical impulses deep into the brain, aiming for the spot where they can reset the depression circuit.
What’s so groundbreaking about the latest approach—so far, performed in just one patient—is that the electrodes didn’t simply deliver constant electrical stimulation. The system could recognize the specific pattern of brain activity associated with the patient’s depressive symptoms and deliver electrical impulses to the brain circuit where it could provide the most relief.
While much more study is needed, this precision approach to deep brain stimulation (DBS) therapy offered immediate improvement to the patient, a 36-year-old woman who’d suffered from treatment-resistant major depressive disorder since childhood. Her improvement has lasted now for more than a year.
This precision approach to DBS has its origins in clinical research supported through NIH’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative. A team, led by Edward Chang, a neurosurgeon at the University of California San Francisco’s (UCSF) Epilepsy Center, discovered while performing DBS that the low mood in some patients with epilepsy before surgery was associated with stronger activity in a “subnetwork” deep within the brain’s neural circuitry. The subnetwork involved crosstalk between the brain’s amygdala, which mediates fear and other emotions, and the hippocampus, which aids in memory.
Researchers led by Andrew Krystal, UCSF, Weill Institute for Neurosciences, attempted in the latest work to translate this valuable lead into improved care for depression. Their results were published recently in the journal Nature Medicine [1].
Krystal and colleagues, including Chang and Katherine Scangos, who is the first author of the new study, began by mapping patterns of brain activity in the patient that was associated with the onset of her low moods. They then customized an FDA-approved DBS device to respond only when it recognized those specific patterns. Called NeuroPace® RNS®, the device includes a small neurostimulator and measures about 6 by 3 centimeters, allowing it to be fully implanted inside a person’s skull. There, it continuously monitors brain activity and can deliver electrical stimulation via two leads, as shown in the image above [2].
Researchers found they could detect and predict high symptom severity best in the amygdala, as previously reported. The next question was where the electrical stimulation would best relieve those troubling brain patterns and associated symptoms. They discovered that stimulation in the brain’s ventral capsule/ventral striatum, part of the brain’s circuitry for decision-making and reward-related behavior, led to the most consistent and sustained improvements. Based on these findings, the team devised an on-demand and immediate DBS therapy that was unique to the patient’s condition.
It will be important to learn whether this precision approach to DBS is broadly effective for managing treatment-resistant depression and perhaps other psychiatric conditions. It will take much more study and time before such an approach to treating depression can become more widely available. Also, it is not yet clear just how much it would cost. But these remarkable new findings certainly point the way toward a promising new approach that will hopefully one day bring another treatment option for those in need of relief from severe depression.
References:
[1] Closed-loop neuromodulation in an individual with treatment-resistant depression. Scangos KW, Khambhati AN, Daly PM, Makhoul GS, Sugrue LP, Zamanian H, Liu TX, Rao VR, Sellers KK, Dawes HE, Starr PA, Krystal AD, Chang EF. Nat Med. 2021 Oct;27(10):1696-1700
[2] The NeuroPace® RNS® System for responsive neurostimulation, NIH BRAIN Initiative.
Links:
Depression (National Institute of Mental Health/NIH)
Deep Brain Stimulation for Parkinson’s Disease and other Movement Disorders (National Institute of Neurological Disorders and Stroke/NIH)
Andrew Krystal (University of California San Francisco)
Katherine Scangos (UCSF)
Edward Chang (UCSF)
NIH Support: National Institute of Neurological Disorders and Stroke
U.S. Surgeon General on Emotional Well-Being and Fighting the Opioid Epidemic
Posted on by Dr. Francis Collins
From September 2019 to September 2020, the Centers for Disease Control and Prevention reported nearly 90,000 overdose deaths in the United States. These latest data on the nation’s opioid crisis offer another stark reminder that help is desperately needed in communities across the land. NIH’s research efforts to address the opioid crisis have been stressed during the pandemic, but creative investigators have come up with workarounds like wider use of telemedicine to fill the gap.
Much of NIH’s work on the opioid crisis is supported by the Helping to End Addiction Long-term (HEAL) Initiative. Recently, the more-than 500 investigators supported by HEAL came together virtually for their second annual meeting to discuss the initiative’s latest research progress and challenges.
As part of the meeting, I had a conversation with Dr. Vivek Murthy, the U.S. Surgeon General. Dr. Murthy served as the 19th U.S. Surgeon General under the Obama Administration and was recently confirmed as the 21st Surgeon General under the Biden Administration. In his first term as America’s Doctor, in which I had the privilege of working with him, Dr. Murthy created initiatives to tackle our country’s most urgent public health issues, including addiction and the opioid crisis. He also issued the nation’s first Surgeon General’s Report on addiction, presenting the latest scientific data and issuing a call to action to recognize addiction as a chronic illness—and not a moral failing.
In 2016, Dr. Murthy sent a letter to 2.3 million healthcare professionals urging them to join a movement to tackle the opioid epidemic. This was the first time in the history of the office that a Surgeon General had issued a letter calling the medical profession to action on this issue. In 2017, Dr. Murthy focused his attention on chronic stress and isolation as prevalent problems with profound implications for health, productivity, and happiness.
Our conversation during the HEAL meeting took place via videoconference, with the Surgeon General connecting from Washington, D.C., and me linking in from my home in Maryland. Here’s a condensed transcript of our chat:
Collins: Welcome, Dr. Murthy. We’ve known each other for a few years, and I know that you’ve talked extensively about the national epidemic of loneliness. What have you learned about loneliness and how it affects our emotional wellbeing?
Murthy: Thanks, Francis. Loneliness and perceived social isolation are profound challenges for communities struggling with addiction, including opioid use disorders. I had no real background in these issues when I started as Surgeon General in 2014. I was educated by people I met all across the country, who in their own way would tell me their stories of isolation and loneliness. It’s a common stressor, especially for those who struggle with opioid use disorders. Stress can be a trigger for relapse. It’s also connected with overdose attempts and overdose deaths.
But loneliness is bigger than addiction. It is not just a bad feeling. Loneliness increases our risk of anxiety and depression, dementia, cardiac disease, and a host of other conditions. However you cut it, addressing social isolation and loneliness is an important public-health issue if we care about addiction, if we care about mental health—if we care about the physical wellbeing of people in our country.
Collins: Vivek, you made the diagnosis of an epidemic of American loneliness back before COVID-19 came along. With the emergence of COVID-19 a little more than a year ago, it caused us to isolate ourselves even more. Now that you’re back as Surgeon General and seeing the consequences of the worst pandemic in 103 years, is loneliness even worse now than before the pandemic?
Murthy: I think there are many people for whom that sense of isolation and loneliness has increased during the pandemic. But the pandemic has been a very heterogenous experience. There are some people who have found themselves more surrounded by their extended family or a close set of friends. That has been, in many ways, a luxury. For many people who are on the frontlines as essential workers, whose jobs don’t permit them to just pick up and leave and visit extended family, these have been very stressful and isolating times.
So, I am worried. And I’m particularly worried about young people—adolescents and young adults. They already had high rates of depression, anxiety, and suicide before the pandemic, and they’re now struggling with loneliness. I mention this because young people are so hyperconnected by technology, they seem to be on TikTok and Instagram all the time. They seem to be chatting with their friends constantly, texting all the time. How could they feel isolated or lonely?
But one of the things that has become increasingly clear is what matters when it comes to loneliness is the quality of your human connections, not the quantity. For many young people that I spoke to while traveling across the country, they would say that, yes, we’re connected to people all the time. But we don’t necessarily feel like we can always be ourselves in our social media environment. That’s where comparison culture is at its height. That’s where we feel like our lives are always falling short, whether it’s not having a fancy enough job, not having as many friends, or not having the right clothing or other accessories.
We talk a lot about resilience in our country. But how do we develop more resilient people? One of the keys is to recognize that social connections are an important source of resilience. They are our natural buffers for stress. When hard things happen in our lives, so many of us just instinctively will pick up the phone to call a friend. Or we’ll get into the car and go visit a member of our family or church. The truth is, if we want to build a society that’s healthier mentally and physically, that is more resilient, and that is also more happy and fulfilled, we have to think about how we build a society that is more centered around human connection and around relationships.
My hope is that one of the things we will reevaluate is building a people-centered society. That means designing workplaces that allow people to prioritize relationships. It means designing schools that equip our children with social and emotional learning tools to build healthy relationships from the earliest ages. It means thinking about public policy, not from just the standpoint of financial impact but in terms of how it impacts communities and how it can fracture communities.
We have an opportunity to do that now, but it won’t happen by default. We have to think through this very proactively, and it starts with our own lives. What does it mean for each of us to live a truly people-centered life? What decisions would we make differently about work, about how we spend time, about where we put our attention and energy?
Collins: Those are profound and very personal words that I think we can all relate to. Let me ask you about another vulnerable population that we care deeply about. There are 50 million Americans who are living with chronic pain, invisible to many, especially during the pandemic, for whom being even more isolated has been particularly rough—and who are perhaps in a circumstance where getting access to medical care has been challenging. As Surgeon General, are you also looking closely at the folks with chronic pain?
Murthy: You’re right, the populations that were more vulnerable pre-pandemic have really struggled during this pandemic—whether that’s getting medications for treatment, needed counseling services, or taking part in social support groups, which are an essential part of the overall treatment approach and staying in recovery. It’s a reminder of how urgent it is for us, number one, to improve access to healthcare in our country. We’ve made huge strides in this area, but millions are still out of reach of the healthcare system.
A potential silver lining of this pandemic is telemedicine, which has extraordinary potential to improve and extend access to services for people living with substance use disorders. In 2016, I remember visiting a small Alaskan fishing village that you can only get to by boat or plane. In that tiny village of 150 people, I walked into the small cabin where they had first-aid supplies and provided some basic medical care. There I saw a small monitor mounted on the wall and a chair. They told me that the monitor is where people, if they’re dealing with a substance use disorder, come and sit to get counseling services from people in the lower 48 states. I was so struck by that. To know that telemedicine could reach this remote Alaskan village was really extraordinary.
I think the pandemic has accelerated our adoption of telemedicine by perhaps five years or more. But we must sustain this momentum not only with investment in broadband infrastructure, but with other things that seem mundane, like the reimbursement structure around telemedicine. I talk to clinicians now who say they are seeing some private insurers go back on reimbursement for telemedicine because the pandemic is starting to get better. But the lesson learned is not that telemedicine should go away; it’s that we should be integrating it even more deeply into the practice of medicine.
The future of care, I believe, is bringing care closer to where people are, integrating it into their workflow, bringing it to their homes and their neighborhoods. I saw this so clearly for many of the patients I cared for who fell into that category of being in vulnerable populations. They were working two, three jobs, trying to take care of their children at the same time. Having a conversation with them about how they could find time to go to the gym was almost a laughable matter because they were literally dealing with issues of survival and putting food on the table for their kids. As a society we have to do more to understand the lives of people who fall into those categories and provide services that bring what they need to them, as opposed to expecting them to come to us.
If we continue in a purely fee-for-service-based environment where people must go multiple places to get their care, we will not ultimately get care to the vulnerable populations that have struggled the most and that are hoping that we will do better this time around. I think we can. I think we must. And I think COVID may just be, in part, the impetus to move forward in a different way that we need.
Collins: Let’s talk a minute about the specifics of the opioid crisis. If we’re going to move this crisis in the right direction, are there particular areas that you would say we really need more rigorous data in order to convince the medical care system—both the practitioners and the people deciding about reimbursement—that these are things we must do?
Murthy: There are a few areas that come to mind, and I’ve jotted them down. It is so important for us to do research with vulnerable populations, recognizing they often get left out. It’s essential that we conduct studies specifically for these populations so that we can better target interventions to them.
The second area is prevention programs. People want to prevent illnesses. I have not met anybody anywhere in the United States who has said, “I’d rather get diabetes first and treat it versus prevent it in the first place.” As silly as that might sound, it is the exact opposite of how we finance health interventions in our country. We put the lion’s share of our dollars in treatment. We do very little in prevention.
The third piece is the barriers faced by primary-care clinicians, who we want to be at the heart of providing a lot of these treatment services. I’ll tell you, just from my conversations with primary-care docs around the country, they worry about not having enough for their patients in the way of social work and social support services in their offices.
Finally, it has become extraordinarily clear to me that social support is one of the critical elements of treatment for substance use disorders. That it is what helps keep people in recovery. I think about the fact that many people I met who struggle with opioid use disorders had family members who were wondering how they could be helpful. They weren’t sure. They said, “Should I just keep badgering my relative to go to treatment? Should I take a tough love approach? What should I do to be helpful?”
This actually is one of the most pressing issues: social support is most often going to come from family, from friends, and from other community members. So, being able to guide them in an evidence-based way about what measures, what forms actually can be helpful to people struggling with opioid use disorders could also be immensely helpful to a group that is looking to provide assistance and support, but often is struggling to figure out how best to do that.
Collins: Vivek, you were focused as Surgeon General in the Obama Administration on the importance of changing how America thinks about addiction—that it is not a moral failing but a chronic illness that has to be treated with compassion, urgency, skill, and medical intervention. Are we getting anywhere with making that case?
Murthy: Sometimes people shy away from addressing the stigma around addiction because it feels too hard to address. But it is one of the most important issues to address. If people are still feeling judged for their disorders, they are not going to feel comfortable coming forward and getting treatment. And others will hesitate to step up and provide support.
I will always remember the young couple I met in Oklahoma who had lost their son to an opioid overdose. They told me that previously in their life whenever they had a struggle—a job loss or other health issue in the family—neighbors would come over, they would drop off food, they would visit and sit with them in their living room and hold their hands to see if they were okay. When their son died after opioid use disorder, it was silent. Nobody came over. It’s a very common story of how people feel ashamed, they feel uncomfortable, they don’t know quite what to say. So they stay away, which is the worst thing possible during these times of great pain and distress.
I do think we have made progress in the last few years. There are more people stepping forward to tell their stories. There are more people and practitioners who are embracing the importance of talking to their patients about substance use disorders and getting involved in treating them. But the truth is, we still have many people in the country who feel ashamed of what they’re dealing with. We still have many family members who feel that this is a source of shame to have a loved one struggling with a substance use disorder.
To me, this is much bigger than substance use disorders. This is a broader cultural issue of how we think about strength and vulnerability. We have defined strength in modern society as the loudest voice in the room or the person with the most physical prowess, the person who’s aggressive in negotiations, and the person who’s famous.
But I don’t think that’s what strength really is. Strength is so often displayed in moments of vulnerability when people have the courage to open up and be themselves. Strength is defined by the people who have the courage to display love, patience, and compassion, especially when it’s difficult. That’s what real strength is.
One of my hopes is that, as a society, we can ultimately redefine strength. As we think about our children and what we want them to be, we cannot aspire for them to be the loudest voice in the room. We can aspire for them to be the most-thoughtful, the most-welcoming, the most-inviting, the most-compassionate voice in the room.
If we truly want to be a society that’s grounded in love, compassion, and kindness, if we truly recognize those as the sources of strength and healing, we have to value those in our workplaces. They have to be reflected in our promotion systems. We have to value them in the classroom. Ultimately, we’ve got to build our lives around them.
That is a broader lesson that I took from all of the conversations I’ve had with people who struggle with opioid use disorders. What I took was, yes, we need medication and assisted treatment; yes, we need counseling services; yes, we need social services and wraparound services and recovery services. But the engine that will drive our healing is fundamentally the love and compassion that come from human relationships.
We all have the ability to heal because we all have the ability to be kind and to love one another. That’s the lesson that it took me more than two decades to learn in medicine. More important than any prescription that I could write is the compassion that I could extend to patients simply by listening, by showing up, by being present in their lives. We all have that ability, regardless of what degrees follow our name.
Collins: Vivek, this has been a wonderful conversation. We are fortunate to have you as our Surgeon General at this time, when we need lots of love and compassion.
Murthy: Thank you so much, Francis.
Links:
Opioids (National Institute on Drug Abuse/NIH)
Opioid Overdose Crisis (NIDA)
Vice Admiral Vivek H. Murthy (U.S. Department of Health and Human Services, Washington, D.C.)
Helping to End Addiction Long-term (HEAL) Initiative (NIH)
Video: Emotional Well Being and the Power of Connections to Fight the Opioid Epidemic (HEAL/NIH)
From Electrical Brain Maps to Learning More About Migraines
Posted on by Dr. Francis Collins
One of life’s greatest mysteries is the brain’s ability to encode something as complex as human behavior. In an effort to begin to unravel this mystery, neuroscientists often zoom in to record the activities of individual neurons. Sometimes they expand their view to look at a specific region of the brain. But if they zoom out farther, neuroscientists can observe many thousands of neurons across the entire brain firing at once to produce electrical oscillations that somehow translate into behaviors as distinct as a smile and a frown. The complexity is truly daunting.
Rainbo Hultman, University of Iowa Carver College of Medicine, Iowa City, realized years ago that by zooming out and finding a way to map all those emergent signals, she could help to change the study of brain function fundamentally. She also realized doing so offered her an opportunity to chip away at cracking the complicated code of the electrical oscillations that translate into such complex behaviors. To pursue her work in this emerging area of “electrical connectomics,” Hultman recently received a 2020 NIH Director’s New Innovator Award to study the most common human neurological disorder: migraine headaches.
A few years ago, Hultman made some impressive progress in electrical connectomics as a post-doctoral researcher in the lab of Kafui Dzirasa at Duke University, Durham, NC. Hultman and her colleagues refined a way to use electrodes to collect electrical field potentials across an unprecedented seven separate mouse brain regions at once. Using machine learning to help make sense of all the data, they uncovered a dynamic, yet reproducible, electrical brain network encoding depression [1].
What’s more, they found that the specific features of this brain-wide network could predict which mice subjected to chronic stress would develop signs of major depressive disorder. As Hultman noted, when measured and mapped in this way, the broad patterns of electrical brain activity, or “Electome factors,” could indicate which mice were vulnerable to stress and which were more resilient.
Moving on to her latest area of research, Hultman is especially intrigued by the fact that people who endure regular migraine attacks often pass through a characteristic sequence of symptoms. These symptoms can include a painful headache on one side of the head; visual disturbances; sensitivity to light, odors, or sound; mood changes; nausea; trouble speaking; and sometimes even paralysis. By studying the broad electrical patterns and networks associated with migraine in mice—simultaneously capturing electrical recordings from 14 brain regions on a millisecond timescale—she wants to understand how brain circuits are linked and work together in ways that produce the complex sequences of migraine symptoms.
More broadly, Hultman wants to understand how migraine and many other disorders affecting the brain lead to a state of heightened sensory sensitivity and how that emerges from integrated neural circuits in the brain. In her studies of migraine, the researcher suspects she might observe some of the same patterns seen earlier in depression. In fact, her team is setting up its experiments to ensure it can identify any brain network features that are shared across important disease states.
By the way, I happen to be one of many people who suffer from migraines, although fortunately not very often in my case. The visual aura of flashing jagged images that starts in the center of my visual field and then gradually moves to the periphery over about 20 minutes is pretty dramatic—a free light show! I’ve wondered what the electrical component of that must be like. But, even with treatment, the headache that follows can be pretty intense.
Hultman also has seen in her own life and family how debilitating migraines can be. Her goal isn’t just to map these neural networks, but to use them to identify where to target future therapeutics. Ultimately, she hopes her work will pave the way for more precise approaches for treating migraine and other brain disorders that are based on the emergent electrical characteristics of each individual’s brain activity. It’s a fascinating proposition, and I certainly look forward to where this research leads and what it may reveal about the fundamentals of how our brains encode complex behaviors and emotions.
Reference:
[1] Brain-wide electrical spatiotemporal dynamics encode depression vulnerability. Hultman R, Ulrich K, Sachs BD, Blount C, Carlson DE, Ndubuizu N, Bagot RC, Parise EM, Vu MT, Gallagher NM, Wang J, Silva AJ, Deisseroth K, Mague SD, Caron MG, Nestler EJ, Carin L, Dzirasa K. Cell. 2018 Mar 22;173(1):166-180.e14.
Links:
Migraine Information Page (National Institute of Neurological Disorders and Stroke/NIH)
Laboratory for Brain-Network Based Molecular Medicine (University of Iowa, Iowa City)
Hultman Project Information (NIH RePORTER)
NIH Director’s New Innovator Award (Common Fund)
NIH Support: Common Fund; National Institute of Mental Health
Lessons Learned About Substance Use Disorders During the COVID-19 Pandemic
Posted on by Dr. Francis Collins
Every spring, I and my colleague Dr. Nora Volkow, Director of NIH’s National Institute on Drug Abuse (NIDA), join with leaders across the country in the Rx Drug Abuse and Heroin Summit. Our role is to discuss NIH’s continued progress in tackling our nation’s opioid crisis. Because of the continued threat of COVID-19 pandemic, we joined in virtually for the second year in a row.
While the demands of the pandemic have been challenging for everyone, biomedical researchers have remained hard at work to address the opioid crisis. Among the many ways that NIH is supporting these efforts is through its Helping to End Addiction Long-Term (HEAL) Initiative, which is directing more than $1.5 billion to researchers and communities across the country.
Here’s a condensed transcript of our April 6th video dialogue, which focused on the impact of the COVID-19 pandemic on people struggling with substance use disorders and those who are trying to help them.
Collins: What have we learned so far through HEAL? Well, one thing HEAL is doing is tackling the need for pain treatments that help people avoid the risks of opioids. This research has uncovered new targets and therapeutics for different types of pain, including neuropathic, post-surgical, osteoarthritic, and chemotherapy induced. We’re testing implanted devices, such as electrodes and non-invasive nerve stimulation; and looking at complementary and integrative approaches, such as phone-based physical therapy for low back pain.
Through HEAL, we’ve launched a first-in-human test of a vaccine to protect against the harmful effects of opioids, including relapse and overdose. We’re also testing a tool that provides pharmacists with a validated opioid use disorder risk measure. The goal is to identify better who’s at high risk for opioid addiction and to determine what kind of early intervention could be put in place.
Despite COVID, many clinical studies are now recruiting participants. This includes family-based prevention programs, culturally tailored interventions for hard-hit American Indian populations, and interventions that address social inequities, such as lack of housing.
We are also making progress on the truly heart-breaking problem of babies born dependent on opioids. HEAL has launched a study to test the effectiveness of a new approach to care that measures the severity of a baby’s withdrawal, based on their ability to eat, sleep, and be consoled. This approach helps provide appropriate treatment for these infants, without the use of medication when possible. We’re also developing novel technologies to help treat neonatal opioid withdrawal syndrome, including a gently vibrating hospital bassinet pad that’s received breakthrough device designation from the FDA.
2020 was an extraordinary year that was tragic in so many ways, including lives lost and economic disasters that have fallen upon families. The resilience and ingenuity of the scientific community has been impressive. Quick pivoting has resulted in some gains through research, maybe you could even call them silver linings in the midst of this terrible storm.
Nora, what’s been at the forefront of your mind as we’ve watched things unfold?
Volkow: When we did this one year ago, we didn’t know what to expect. Obviously, we were concerned that the stressors associated with a pandemic, with unknowns, are factors that have been recognized for many years to increase drug use. Unfortunately, what we’ve seen is an increase in drug use of all types across the country.
We have seen an exacerbation of the opioid epidemic, as evidenced by the number of people who have died. Already, in the 12 months ending in July 2020, there was a 24 percent increase in mortality from overdoses. Within those numbers, there was close to a 50 percent increase in mortality associated with fentanyl. We’re also seeing an increase, not just in deaths from fentanyl and other synthetic opioids, but in deaths from stimulant drugs, like cocaine and methamphetamine. And the largest increases have been very much driven by drug combinations.
So, we have the perfect storm. We have people stressed to their limits by decreases in the economy, the loss of jobs, the death of loved ones. On the other hand, we see dealers taking the opportunity to bring in drugs such as synthetic opioids and synthetic stimulants and distribute them to a much wider extent than previously seen.
Collins: On top of that, people are at risk of getting sick from COVID-19. What have we learned about the risks of coronavirus illness for people who use drugs?
Volkow: It is a double whammy. When you look at the electronic health records about the outcomes of people diagnosed with substance use disorders, you consistently see an increased risk for getting infected with COVID-19. And if you look at those who get infected, you observe a significantly increased risk of dying from COVID.
What’s driving this vulnerability? One factor is the pharmacological effects of these drugs. Basically, all of the drugs of abuse that result in addiction, notably opioids, damage the cardiopulmonary system. Some also damage the immune system. And we know that individuals who have any disruption of cardiovascular health, pulmonary health, immune function, or metabolism are at higher risk of getting infected with COVID-19 and having adverse outcomes.
But there’s another factor that’s as important—one that’s very tractable. It is the way in which our society has dealt with substance use disorders: not actually treating them as a disease that requires intervention and support for recovery. The stigmatization of individuals with addiction, the lack of access to treatment, the social isolation, have all created havoc by making these individuals so much more vulnerable to get infected with COVID-19.
They will not go to a doctor. They don’t want to be stigmatized. They need to go out into the streets to get access to the drugs. Many times, they don’t have a choice of what drugs to take because they cannot afford anything except what’s offered to them. So, many, especially those who are minorities, end up homeless or in jails or prison. Even before COVID, we knew that prisons and jails are places where infections can transmit extraordinary rapidly. You could see this was going to result in very negative outcomes for this group of individuals.
Collins: Nora, tell us more about the trends contributing to the current crisis. Maybe three or four years ago, what was going straight up was opioid use, especially heroin. Then, fentanyl started coming up very fast and that has continued. Now, we are seeing more stimulants and mixing of different types of drugs. What is the basis for this?
Volkow: At the beginning of the opiate pandemic, mortality was mainly associated with white Americans, many in rural or semi-suburban areas of the Appalachian states and in New Mexico and Arizona. That has shifted. The highest increase in mortality from opioids, predominantly driven by fentanyl, is now among Black Americans. They’ve had very, very high rates of mortality during the COVID pandemic. And when you look at mortality from methamphetamine, it’s chilling to realize that the risk of dying from methamphetamine overdose is 12-fold higher among American Indians and Alaskan Natives than other groups. This should make us pause to think about what’s driving these terrible racial disparities.
As for drug combinations, many deaths from methamphetamine or cocaine—an estimated 50 percent—are linked to these stimulant drugs being combined with fentanyl or heroin. Dealers are lacing these non-opioid drugs with cheaper, yet potent, opioids to make a larger profit. Someone who’s addicted to a stimulant drug like cocaine or methamphetamine is not tolerant to opioids, which means they are going to be at high risk of overdose if they get a stimulant drug that’s laced with an opioid like fentanyl. That’s been contributing to the sharp rise in mortality from non-opioid drugs.
Collins: I’m glad you raised the issue of health disparities. 2020 will go down as a year in which our nation had to focus on three public health crises at once. The first is the crisis of opioid use disorder and rising mortality from use of other drugs. The second is COVID-19. And the third is the realization, although the problem has been there all along, that health disparities continue to shorten the lives of far too many people.
The latter crisis has little to do with biology, but everything to do with the way in which our society still is afflicted by structural racism. We at NIH are looking at this circumstance, realizing that our own health disparities research agenda needs to be rethought. We have not fully incorporated all the factors that play out in health inequities and racial inequities in our country.
You were also talking about how stimulants have become more widespread. What about treatments for people with stimulant use disorders?
Volkow: For opioid addiction, we’re lucky because we have very effective medications: methadone, buprenorphine, naltrexone. On top of that, we have naloxone, Narcan, that if administered on time, can save the life of a person who has overdosed.
We don’t have any FDA-approved medication for methamphetamine addiction, and we don’t have any overdose reversal for methamphetamine. At the beginning of this year, we funded a large clinical trial aimed at investigating the benefits of the combination of two medications that were already approved as anti-depressants and for the treatment of smoking cessation and alcoholism. It found this combination significantly inhibits the urge to take drugs and therefore helps people stay away from use of methamphetamine. Now, we want to replicate these findings, and to tie that replication study in with guidelines from the FDA on what is needed to approve our new indication for these medications. Why? Because then insurance can cover it, and that will increase the likelihood that people will get treated.
Another exciting possibility is a monoclonal antibody against methamphetamine that’s in Phase 2 clinical trials. If someone comes into the emergency room with an overdose of a combination of opioid and methamphetamine, naloxone often will not work. But this monoclonal antibody with naloxone may offer a greater likelihood of success.
Another thing that’s promising is that investigators have been able to modify monoclonal antibodies so they stay in the bloodstream for a longer time. That means we may someday be able to use this passive immunization approach as a treatment for methamphetamine addiction.
Collins: That’s good to hear. Speaking of progress, is there any you want to point to within HEAL?
Volkow: There’s a lot of excitement surrounding medication development. We’re interested in developing antidotes that will be more effective in reversing overdose deaths from fentanyl. We’re also interested in providing longer lasting medications for treatment of opioid use disorders, which would improve the likelihood of patients being protected from overdoses.
The Justice Community Opioid Innovation Network (JCOIN) is another HEAL landmark project. It involves a network of researchers that is working with judges and with the workers in jail and prison systems responsible for taking care of individuals with substance use disorders. Through this network, we’ve been able to start to harmonize practices. One thing that’s been transformative in the jail and prison system has been the embracing of telehealth. In the past, telehealth was not much of a reality in jails and prisons because of the fear of it could lead to communications that could perhaps be considered dangerous. That’s changed due to COVID-19. Now, telehealth is providing access to treatment for individuals in jail and prison, many of them with substance use disorders.
Also, because of COVID, many nonviolent individuals in jails and prisons were released. This gives us an opportunity to evaluate how best to help such individuals achieve recovery from substance use disorders. Hopefully we can generate data to show that there are much more effective strategies than incarceration for dealing with substance use disorders.
The HEALing Communities Study, involves Massachusetts, New York, Ohio, and Kentucky—four of the states with the highest rates of mortality from overdoses from the inception of the opioid epidemic. By implementing a battery of interventions for which there is evidence of benefit, this ambitious study set out to decrease overdose mortality by 40 percent in two years. Then, came COVID and turned everything upside down. Still, because we consolidated interactions between agencies, we’ve been able to apply support systems more efficiently in those communities in ways that have been very, very reinforcing. Obviously, there’ve been delays in implementation of interventions that require in-person interactions or that involve hospital emergency departments, which have been saturated with COVID patients.
We’ve learned a lot in the process. I may be too optimistic, but I do believe that we can stay on goal.
Collins: Now, I’d like to transition to a few questions from people who subscribe to the HEAL website. Announced at this meeting three years ago, the HEAL Initiative involves research participants and patients and stakeholders—especially people who have lived experience with pain, addiction, or both.
Let’s get to the first question: “What is NIH doing through HEAL to address the stigma that prevents people who need opioid medications for treatment from getting them?”
Volkow: A crucial question. As we look at the issue of stigma, we need to recognize that there are structural issues in how our society is prioritizing the importance of substance use disorders and the investments devoted to them. And we need to recognize that substance use disorder doesn’t exist in isolation; it is frequently comorbid with mental illness.
We need to listen. Some of the issues that we believe are most problematic are not. We need to empower these communities to speak up and help them do so. This is probably one of the most important things that we can do in terms of addressing stigma for addiction.
Collins: Absolutely. The HEAL Initiative has a number of projects that are focusing on stigma and coming up with tools to help reduce this. And here’s our second question: “In small communities, how can we provide more access to medications for opioid use disorder?”
Volkow: One project funded through HEAL was to evaluate the effectiveness of community pharmacies for delivering buprenorphine to individuals with opioid use disorder. The results show that patients receiving buprenorphine through community pharmacies in rural areas had as good outcomes as patients being treated by specialized clinicians on site.
Another change that’s made things easier is that in March 2020, the DEA relaxed its rules on how a physician can prescribe buprenorphine. In the past, you needed to go physically to see a doctor. Now, the DEA allows a patient to be initiated on buprenorphine through telehealth, and that’s opened the possibility of greater access to treatment in rural communities.
My perspective is let’s look at innovative ways of solving problems. Because the technology is changing in so many ways and so rapidly, let’s take advantage of it.
Collins: Totally with you on that. If there’s a silver lining to COVID-19, it’s that we’ve been forced to take stock of the ways we’ve been doing things. We will learn from this pandemic and change the way we approach so many things in health and medicine as a result. Certainly, opioid use disorder ought to be very high on that list. Let’s move on to another question: “What is the HEAL initiative doing to promote prevention of opioid use?”
Volkow: This is where the HEAL initiative is aiming to provide alternative treatments for the management of pain that reduce the risk of addiction.
Then there’s the issue of prevention in people who start to take opioids because they either want to get high or escape. With the COVID pandemic, we’ve seen increases in anxiety and in depression. Those are factors that can put a teenager or young adult on a trajectory for higher risk of substance use disorders.
So, what is HEAL doing? There is prevention research specifically targeted, for example, at the transition from adolescence to young adulthood. That is the period of greatest vulnerability of uptake of opioids, or drugs of misuse. We’re also targeting minority groups that may be at very, very high risk. We want to be able to understand the factors that make them more vulnerable to tailor prevention interventions more effectively.
Collins: Today, we’ve shared some of the issues that NIH is wrestling with in its efforts to address the crisis of opioid misuse and overdose, as well as other drugs that are now very much part of the challenge. To learn more, go to the HEAL website. You can also send us your thoughts through the HEAL Idea Exchange.
These developments give me hope in the wake of a very difficult year. Clearly, we still have the capacity to work together, we are resilient, and we are determined to put an end to our nation’s opioid crisis.
Volkow: Francis, I want to thank you for your incredible leadership and your support. I hope the COVID pandemic will bring forth a more equitable system, in which all people are given the chance for resilience that maximizes their life, happiness, and productivity. I think science is an extraordinary tool to help us do that.
Links:
Video: The 2021 Rx Drug Abuse & Heroin Summit: Francis Collins with Nora Volkow (NIH)
COVID-19 Research (NIH)
Helping to End Addiction Long-term (HEAL) Initiative (NIH)
HEAL Idea Exchange (NIH)
National Institute on Drug Abuse (NIH)
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