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Loss is unavoidable on the human journey. Where there is loss, grief follows. Grief can be overwhelming due to the intensity of emotions involved. In the aftermath of a major loss, people often struggle to return to their routines in a way that honors and makes space for their bereavement. Grief rituals offer a powerful means of working with and healing from loss that can be incorporated into daily life. Personalized grief rituals allow for greater flexibility, customization, and repetition. This article presents an easy-to-follow template for designing a grief ritual tailored to your particular loss. Carrying out such a ritual is an empowering and hands-on way of working with your grief. A grief ritual may not be appropriate in some cases. Consult with a professional before conducting a grief ritual if you struggle with depression, suicidality, or other mental health issues, or if you feel ill-equipped to handle the intense emotions that may arise. What is a Ritual? Any event or activity with structure, intention, and an element of the sacred can be a ritual. Some examples include meditating each morning, singing “happy birthday” at a celebration, or planting and tending a memorial garden. Regardless of the content, rituals create a space to honor what matters most and to welcome insight, growth, and healing. How Rituals Help with Grief The English word “grief” derives from a Latin word that means “heavy,” “weighty,” and “burdensome.” Rituals help alleviate the burden of grief after a major loss. They do this by promoting acceptance of the loss, emotional expression, and a feeling of control. Rituals also help maintain a bond with what has been lost and provide an opportunity for reflecting on how to go forward. Carrying out a ritual connects a person to whatever they consider sacred, be it a higher power, a state of consciousness, or their most cherished values. GRIEF RITUALS ​ ​ ✔ Acceptance of loss ​✔ Sense of control ​✔ Processing of emotions ✔ Creation of meaning ✔ Maintenance of bond with deceased ✔ Comforting routine ✔ Expression of beliefs & values ✔ Healing, growth, & insight Adopting a Personal Grief Ritualfgxhdfgjugf To be effective, a grief ritual should be tailored to your particular loss, belief system, and immediate environment. Below are steps you can follow to design a grief ritual that is right for your situation. Feel free to make adjustments based on your culture, setting, and religious or spiritual beliefs. ​Grief Ritual Steps ​1. Choose a meaningful object 2. Make it sacred ​3. Incorporate movement ​4. Interact with chosen object ​5. Create closure and repeat Choose a Meaningful Object Grief rituals benefit from incorporating a meaningful physical object. If possible, select an object with a connection to your loss. If you are grieving the loss of a loved one or relationship, this might be a cherished piece of jewelry, an article of clothing they wore, a gift they gave you, a letter they wrote, or a photograph. If your loss does not involve a person, you may still be able to find an object related to the loss. For example, if you are grieving the end of a job, you could choose an object from that role—a pen, ID card, uniform, or business card. If you are unable to think of an object, select something with symbolic value from the natural environment—a rock, flower, seashell, or feather. Make it Sacred Rituals should have an element of sacredness to distinguish them from mundane activities, such as getting dressed, cleaning, or driving to work. Lighting a candle, visiting a special place, or reciting a prayer, mantra, or intention are all good options for marking the start and conclusion of your ritual and emphasizing its sacredness. Rituals should also include steps performed in a certain order. This provides a structure that guides you through the ritual, which can be helpful if you are overwhelmed with emotion. Incorporate Movement Research suggests that connecting with your body can help with expressing and processing difficult emotions, which is one of the most important benefits of a grief ritual. Incorporating movement into your grief ritual can be an effective way to do this. A walk in nature—even if just around the block or in a park—can serve this function. If you are mourning the loss of a person, you might walk in a place that reminds you of them. Some find it meaningful to visit the site where their loved one died or where their remains are located. If it is not possible to go for a walk, consider whether there are other ways to use movement in your ritual. For example, you could dance to a song that speaks to your loss. If you live near water where it is safe to swim, you could immerse yourself or tread water as part of your ritual. Interact with Chosen Object Rather than just having an object present, grief experts recommend using the object in some way. This symbolizes moving the pain of grief to a place where it can be worked with and transformed. For example, if you wrote a letter expressing your feelings about a relationship that ended, you could shred and bury it as a way of releasing your emotions. If you chose a rock as your object, imagine your anger or guilt being absorbed into it, and then drop the rock into deep water as a way of letting go of what burdens you. If your object is a feather, place it in a stream, and watch as it slowly fades from view. Take adequate time to feel and express any emotions that come up in your grief ritual. Another option is to create a small altar somewhere in your home. Place your chosen object on the altar and treat it as a sacred space where you can regularly meditate, pray, or sit in quiet contemplation. Create Closure & Repeat After performing your ritual, create a sense of closure before returning to your day. Some good options are reciting a mantra, expressing an intention, praying, meditating, or extinguishing a candle you lit to begin the ritual. This helps mark the end of your ritual and the return to your normal activities. Rituals often increase in power and significance when repeated. If your ritual is elaborate or time-consuming, it may make sense to repeat it on an occasional basis, such as on the anniversary of the loss. But simpler rituals can often be integrated into your daily life. For example, you could light a candle and meditate or pray each morning to start your day. Or you could go on a short walk in the evenings as a way of reflecting on your loss. Experiment with what works best for you. Grief Rituals in Action Below are examples of how two people designed effective grief rituals using the previously outlined steps: End of a Relationship Daniel is struggling in the months following his divorce. He is devastated by the end of his marriage, but also angry and hurt, especially about his ex-wife's affair. Here’s how Daniel created a ritual to work with his grief: ​Ritual Step ​Action ​Choose a meaningful object ​Daniel decides to write a letter to his ex-wife expressing his anger and other emotions. Make it sacred Daniel finds a quiet place to write the letter and lights a candle to mark the start of his ritual. Incorporate movement Daniel walks to an empty field near his house. He then digs a hole in the ground. Interact with chosen object Daniel reads the letter aloud, expresses his emotions, shreds the letter, and places the many pieces into the hole. Create closure & repeat Daniel plants a sapling in the hole with the shredded letter, returns home, and decides to revisit the site in a month. Death of a Loved One Marisa is heartbroken after losing her older sister, Gabriela. In addition to mourning her sister’s passing, Marisa is sad that she did not get a chance to say goodbye. This is how Marisa designed and carried out a ritual to aid her grief process: ​Ritual Step Action Choose a meaningful object On one of her walks, Marisa finds a colorful feather, which reminds her of her sister’s love of birds. Make it sacred Marisa decides to carry out her ritual at a nearby stream in a beautiful setting that feels special to her. Incorporate movement ​Marisa walks through the woods to the stream and finds a quiet spot on its banks. Interact with chosen object Marisa says goodbye to her sister and wishes her spirit well. She then gently releases the feather into the stream. Create closure & repeat After the feather disappears into the distance, Marisa returns home, resolving to revisit the ritual site every weekend. Your grief ritual can and should look different from these examples, as it will be unique to your loss, beliefs, and preferences. Be creative as you decide how to incorporate the elements mentioned in the article. Remember to include each of the outlined steps in whatever ritual you choose: Choose a meaningful object, make it sacred, incorporate movement, interact with chosen object, and create closure and repeat. While not a cure for loss, carrying out a well-designed personal grief ritual has many potential benefits, such as helping you accept the loss, process your emotions, have a sense of control, and maintain your bond with the deceased, among others. Repeating your ritual and making it part of your routine can increase these benefits and give meaning and structure to your life.

WASHINGTON (Reuters) -The U.S. surgeon general declared gun violence in the country a public health crisis on Tuesday, calling on Americans to act to prevent rising firearm-related deaths and their cascading effects, particularly on Black Americans, young Americans and other populations. In the first-ever public health advisory on gun violence, the nation's top public health official, Vivek Murthy, outlined what he called devastating and far-reaching consequences to the public's well-being and called for more research funding, better mental health access and other steps such as secure storage to reduce harm. "Firearm violence is an urgent public health crisis that has led to loss of life, unimaginable pain, and profound grief for far too many Americans," he said in a statement. Murthy said the impact of gun violence spreads far beyond the staggering number - 50,000 a year - of lives lost. It impacts millions of people who have been shot and survived it, as well as those who have witnessed gun violence, lost family members or who learn about through the news. In 2020, gun violence became the leading cause of death among U.S. children and adolescents, the report noted. The firearm mortality rate among youths in the U.S. is 11 times higher than in France, 36 times higher than in Germany and 121 times higher than in Japan, according to the advisory. The rate of firearm-related deaths has been steadily rising, Murthy warned, with more than half of those in 2022 driven by suicides followed by homicides and accidental deaths. Studies have shown the increase in firearm-related fatalities among U.S. youth has taken a disproportionate toll on Black communities. Mass shootings, which draw outsized attention despite representing a small percentage of firearm-related deaths, have also increased in recent years. The country has seen more than 600 such incidents in each full year since 2020, according to the Gun Violence Archive, which defines a mass shooting as involving at least four victims. In television interviews, Murthy compared his latest effort to previous public health campaigns that targeted cigarette smoking and promoted seatbelt use. "One of my goals here is to take out of the realm of politics and into the realm of public health," Murthy said on MSNBC. But many of the solutions that the report recommended, such as expanding background checks and banning assault-style weapons, have little chance of becoming law, with Republican lawmakers in Congress staunchly opposed to virtually all gun limits as violations of the U.S. Constitution's guaranteed right to bear arms. Murthy last year issued public health advisories on the harm that social media causes to young people's mental health and on the crisis of loneliness and isolation. Last week, he called for social media warning labels to protect adolescents. Former congresswoman and gun shooting survivor Gabby Giffords, who founded the Giffords anti-gun violence organization after she was wounded in the head in 2011 during a mass shooting, called on policymakers and the U.S. government to heed the surgeon general's warning. "I have seen firsthand how shootings are a major threat to Americans' lives and well-being, and our leaders must view the problem as the public health crisis it is," Giffords said in a statement. The National Rifle Association decried the advisory as an "extension of the Biden administration's war on law-abiding gun owners." (Reporting by Susan Heavey, Doina Chicau and Nandita Bose in Washington and Chandni Shah in Bengaluru; Additional reporting by Joseph Ax and Caroline Humer; Editing by Andrew Heavens, Chizu Nomiyama and Aurora Ellis) Note: This article originally appeared on Medscape .

During the coronavirus pandemic, public health measures and restrictions impacted in-person health care visits, leading to a surge in telehealth services as a way of accessing assessment and treatment. Particularly in mental health care, telehealth saw a significant rise, and usage remains high even post-pandemic. However, despite the increased utilization of telehealth services, there's a limited understanding of the availability and structure of these services. What did the researchers do? In an NIMH-funded study, researchers led by Jonathan Cantor, Ph.D. , of the RAND Corporation investigated the availability of different types of telehealth services and the time it took patients to access telehealth care. Between December 2022 and March 2023, researchers contacted more than 1,900 outpatient mental health care facilities to ask about telehealth services. The underlying sample came from outpatient mental health treatment facilities, not individual practitioners. The researchers used a secret shopper approach, using a script that mirrored information a prospective patient might ask when inquiring about telehealth services. The secret shoppers asked about the availability of telehealth services for treating major depressive disorder, generalized anxiety disorder, or schizophrenia. They also asked about the specific services offered via telehealth (behavioral therapy, medication management, diagnostic services) and the number of days they would have to wait before having their first telehealth appointment. Both men and women served as secret shoppers, and the names used by the shoppers were chosen to reflect a variety of racial and ethnic backgrounds. What did the researchers find? Out of the more than 1,900 facilities contacted, the researchers received replies from 1,404. Among these, 1,221 were accepting new patients. Of those 1,221 facilities, 80% (980) offered telehealth services. Out of the 980 treatment facilities that offered telehealth services: 97% provided counseling services 77% provided medication management 96% provided diagnostic services Among the facilities that responded to the telehealth question, the researchers found: Not-for-profit and for-profit private treatment facilities were more likely to offer telehealth services than public treatment facilities. Treatment facilities in metropolitan areas were more likely than non-urban areas to offer medication management but less likely to offer diagnostic services. The average wait time for a telehealth appointment was 14 days (ranging from 4 to 75 days, depending on the facility contacted). What do the findings mean? The researchers found that some of the facilities they initially reached out to for information did not respond, suggesting that people looking for any type of mental health care may experience barriers to accessing it. Of the facilities that did respond, most were accepting new patients, and most provided telehealth services; however, the availability of those services and the type of care offered varied by location and state. This suggests there may be disparities in access to telehealth services across the United States. The researchers note that telehealth services and availability may differ at health centers not included in this study and that the availability of technology that makes telehealth possible—such as broadband services—was not examined in this analysis. Note: This article originally appeared on NIMH .

It is officially summer in the northern hemisphere, the season for summer vacation travel. My wife and I are on vacation in Manhattan. Actually, perhaps we are on an ongoing vacation of sorts since I retired from my formal psychiatric clinical and administrative work a dozen years ago. Usually, nonprofessional travel is considered as a vacation in the sense of a getaway from the routine. Perhaps it can be more than that. It can be part of psychiatry. Travel can perhaps be therapeutic. Travel can also be part of a new focus in psychiatry called lifestyle psychiatry.1 Lifestyle psychiatry is the theme of the 2025 American Psychiatric Association Annual Meeting. The Wall Street Journal  has long had a section on Lifestyle in their daily paper, and Travel is one of the subsections. Taking travel as a therapeutic lifestyle connects the 2 threads. This sort of focus has been developed over recent years by the School of Life, an organization begun in England in 2016 and now global. Its goal has been to translate mental health principles into everyday life. I think they have done that remarkably well, and in a way that is easy enough for the public to understand and appreciate, but with some sophistication. Therapeutic travel means to consciously pick a destination that is likely to inspire and enchant in a way that enhances well-being, maybe even be healing. In one of products of the School of Life, A Therapeutic Atlas , images of particular places, also accompanied by short essays, illustrate the potential places that can liberate our minds in different ways.2 This atlas can be read in conjunction with planned travel, afterwords, or I suppose, even to review past travel with a new perspective. Although most of the places in the book may seem exotic, really, the travel can also be staycations at home. In the section of the atlas on Holidays, I found the Nightclubs on pages 54-55. I was attracted to that because it is in Manhattan—where we have headed. The time in the book is 1978, with an image of the infamous Studio 54, with the statement: “It can take serious pain before we learn to dance with true silliness.” I think that I have learned over the years, or at least have been told, that I can dance pretty silly. My wife and I never went to such clubs, but instead jazz clubs which do not often include dancing. Just the music. By you can jive and bob around in your seat, and be swept away with the healing force of music in a connected and collective multicultural audience. We are planning to go to a special place and event, billed as New York’s biggest, which I likely will cover in the next column. A hint: maybe it has something to do with one of my favorite songs and pictures of Rusti and I dancing, titled “Dancing to the End of Love,” after the song of that name by Leonard Cohen. Sort of accompanying the book is a set of Travel Therapy cards, designed to “deepen and transform the experience of travel.” The first is “What is this destination trying—in its way—to teach you?” A later card is: “How could you change your life in some way because of what you have seen here?” Rusti and I may also share some of our answers. Perhaps you or your patients have had some therapeutic travel. If so, please let us know. Note: This article originally appeared on Psychiatric Times .

The world is facing an era of climate crisis. The year 2023 was the warmest on record since the Industrial Revolution, underscoring the undeniable evidence of ongoing global warming. This presents a critical issue, as global average temperatures have now surpassed the 1.5 °C threshold established by the Paris Agreement in 2015 on multiple occasions and in various regions across the globe. The current trajectory is concerning, with predictions indicating that temperatures will continue to rise if no action is taken. The recent Conference of Parties (COP) 28 United Nations Climate Change Conference in Dubai, United Arab Emirates, resulted in a consensus among parties to initiate an energy transition toward a phaseout of fossil fuels. This is a crucial step, as fossil fuels are a major source of greenhouse gases, pollution, and global warming. The ramifications of rising temperatures are profound, affecting the planet, states, communities, and individuals in diverse and interconnected ways. Climate is a complex system characterized by multiple pathways of development, alternating periods of gradual and rapid change, feedback loops and nonlinear dynamics, thresholds, tipping points, and shifts among pathways.2 In a globalized society, all is intertwined. Ecosystems are subjects in a complex network of interactions, and each part of the world that is affected by the effects of climate change has consequences on the others. In the context of climate change, these characteristics can lead to acute, subacute, and chronic environmental events and changes. The impact of climate change–related events can vary, from acute to chronic occurrences that are experienced directly or indirectly. Acute events are the fast-onset disasters, such as extreme weather events (eg, typhoons, cyclones, floods, wildfires, heat waves), while the subacute events are the slow-onset events such as droughts. Chronic events refer to slow environmental changes, such as the rise of sea levels and, in the future, the disappearance of islands (eg, the Pacific Islands) or cities, loss of biodiversity, and/or mass extinction. All these events entail both direct and indirect impacts that can coexist, overlap, and be nested within each other. The influence of these events on mental health and well-being can also be direct or indirect. Individuals can be directly affected by experiencing climate-related extreme events such as floods and tornadoes. This exposure involves a physical risk and, at first, attempting to survive the disaster, which may cause trauma or death, exposure to vector-borne diseases and disaster-related pathologies, as well as mental diseases like trauma, depression and other mood disorders, anxiety disorder, substance abuse, and suicide. Additionally, witnessing the calamities, living near the affected area, and learning about an event, even from a distance, are all ways an individual may experience indirect repercussions from climate events. The experience of subacute and chronic events also leads to onset of the so-called psychoterratic syndromes, emotional states specifically correlated with living or witnessing climate change. These emotions include solastalgia, eco-anxiety, eco-grief, eco-trauma, climate anxiety, and ecological posttraumatic stress disorder (PTSD), as well as denial and apathy. All the extreme and slow-onset events carry societal costs in terms of population mental health, premature deaths, reduced well-being, breakdown of communities or societies, disruption to socioeconomic and political conditions, and increased forced migration and conflicts. Additionally, different individuals may experience climate change in different ways. Vulnerable individuals or populations may be particularly sensitive to these types of events and may be more prone to developing psychiatric disorders. Vulnerable groups include women, youth, and the elderly, individuals with preexisting physical or mental illnesses, Indigenous populations, and individuals with low socioeconomic status. Some scientists studying the climate and eco-activists may be more exposed to climate-related information and, therefore, more sensitive to its impact. Environmental Determinants The mind and the planet are connected deeply, on multiple levels, and in a complex way. Numerous climate determinants have been linked to mental health, and understanding this is crucial for promoting well-being and developing effective interventions to address mental health challenges in these times of climate crisis. The determinants of mental health operate at 4 levels (Figure), interact with each other, and are influenced by various protective and risk factors. The determinants of health are defined as the range of personal, social, economic, and environmental factors that influence physical and mental health. Recognizing the environment as a significant factor affecting individual health entails acknowledging the importance of the environment as a determinant of mental health. The environmental determinant is both from nature (the non-human element that includes geographical areas and encompasses the interactions among all living species, as well as the elements and phenomena present in Earth’s lands, waters, and biodiversity) and from the built environment (human-made surroundings that serve as the backdrop for human activities like living, working, and recreation).8 In the era of climate change, environmental determinants can influence each of the 4 levels of mental health. At the personal level, an increasing number of individuals are exposed to the effects of climate change, both extreme and slow-onset events. These have an impact on mental health, especially in vulnerable individuals. Disconnection from the natural environment and increased urbanization also contribute to environmental influences on personal health. Living in the city is a risk factor due to the adverse effects of air pollution, noise pollution, and distance from green environments. At the family and community levels, having low socioeconomic status, being a member of an already at-risk group, and seeing one’s homeland and community places being threatened by climate change can be a risk factor for adverse climate effects. Protective community factors are given by the level of closeness and cohesion within a group following a disaster and being together and coping through pro-environmental actions. At the society level, indirect psychosocial impacts are triggered by weather disasters, infrastructure damages, or the experience of economic hardship.3 Furthermore, the escalation of climate change may push the planet past critical thresholds, potentially leading to societal collapse. However, the economic and political aspects of society may cooperate for mitigation of climate change. For example, during COP 28, a “loss and damage fund” was established to address the damage of climate disasters and to support the vulnerable communities that are affected by it. Ecotherapy Nature is an environmental determinant of mental health and well-being. Numerous studies suggest that experiences in nature can be beneficial for health and well-being. Nature is effective for mitigating medical disorders such as hypertension and cardiovascular disease, obesity, diabetes, postsurgical recovery, and sleep disturbance, and can help increase attentiveness, brain capacity, and creativity. Much evidence suggests that spending time in nature has mental health benefits and can decrease the risk of mental illnesses and psychosocial conditions like mood disorders, depression, anxiety disorder, stress, and PTSD. For children, spending time in nature is beneficial for behavioral disorders such as attention-deficit/hyperactivity disorder and for lowering the risk of onset of psychiatric disorders in older age. Activities in nature come in many forms, including therapeutic horticulture, pet therapy, therapeutic use of agricultural landscapes and farming practices, conservation work, physical exercise outdoor in parks and the countryside, nature-related arts and crafts, and specific ecotherapy techniques. Although many of these activities can be done alone, they may also be done socially to increase the sense of community and cohesion in a specific group. In general, spending time in nature is beneficial for physical, mental, and emotional health, so clinicians should encourage patients to engage in these types of activities. Being aware of the effects of climate change can also lead individuals to get more involved in pro-environmental behaviors. These actions may involve activism in environmental organizations, non-activist behavior in the public sphere (eg, petitioning on environmental issues), private actions (eg, saving energy, purchasing recycled goods), and organizational behavior (eg, product design). The more these actions are perceived as meaningful, the stronger their positive impact on subjective well-being will be. This type of behavior benefits not only the individual but also the community and the entire planet. The connection that occurs between climate change and individuals can be positive when it starts consciously from the individuals themselves. Concluding Thoughts Being aware of climate change adds a layer of complexity to discussions surrounding individual well-being and mental health. Mental health is influenced not only by individual biology, but also by social, ecological, and environmental determinants. Recognizing and addressing these connections comprehensively is essential for promoting individual and collective well-being. Mental health clinicians must be aware of the effects of climate change on mental health in individuals and communities and they must encourage individuals to engage in ecotherapy techniques, pro-environmental behaviors, and behaviors promoting social and community cohesion. Note: This article originally appeared on Psychiatric Times .

Keypoint: Judith Joseph, MD, MBA, shares her journey of balancing clinical work with social media mental health advocacy. CLINICAL CONVERSATIONS With a mission of “Bridging the gap between advanced research and real-world understanding,” Judith Joseph, MD, MBA, finds opportunities to better herself, the field of psychiatry, and mental health education for the general public. In fact, based on her reach and success, the US House of Representatives recently acknowledged her popular presence on social media, where she leverages her experience, clinical research, and expertise to help patients as well as to advocate for better treatments. Joseph, who is a clinical assistant professor in the department of Child and Adolescent Psychiatry at New York University’s Langone Medical Center, also serves as a medical board member for the national nonprofit organization Let’s Talk Menopause and chair of the Women in Medicine Board at Columbia University Vagelos College of Physicians and Surgeons. She is also the principal investigator at Manhattan Behavioral Medicine, where she has been part of more than 60 clinical trials and has mentored numerous early career investigators, and she has worked as a child and adolescent and adult psychiatrist. Psychiatric Times invited Joseph to share her journey, lessons learned, and hopes for the future of psychiatry. Psychiatric Times: How did your social media journey begin? Judith Joseph, MD, MBA: When I was a first-year fellow at New York University in the department of child and adolescent psychiatry, a reporter came to the psychiatric emergency department and interviewed me about the services that were being offered. When I read the article, I was disappointed in my interview, and I asked the director of education at my fellowship if the department would enroll me in a media training course. My director’s response was a Socratic one. He said, “Judith, you should develop the course yourself. And then when you finish writing the course, you should teach it to the rest of us.” Initially I thought that he was joking, but he wasn’t. In fact, he suggested that I focus on media training as the topic of my second year senior project during my fellowship program. I wrote the course after doing extensive research in journalism and medical media reporting, and then I taught the course to the NYU child psychiatry fellows and NYU film undergraduate students who were taking CAMS (Child and Adolescent Mental Health Studies Minor) courses at NYU. The course is titled “Meet The Press,” and I am in my tenth year teaching this course at NYU. During this course, I teach doctors and health care professionals how to give press interviews. The first half of the course is skills based in which I teach specific tools and skills, and the second half of the course is practical and consists of videotaped mock press interviews during which the doctors learn how to implement the tools that were taught in the first half of the course. We play back the video mock interviews to the class in real-time so that their peers and I can give them constructive feedback. I started to become active on social media so that I could teach my students. I had no idea that I would have this much personal and career success in such a short period of time. Teaching this course opened up so many opportunities for me. I used my media skills to give press interviews with local radio and news stations, and eventually I found myself as a regular medical media expert, appearing from 2017 through the present on national television shows such as the Today Show, Dr Oz, ABC News, and many more. This exposure led to consulting work as a medical writer. I worked on a fiction series, The Crowded Room, starring and produced by Tom Holland for Apple TV. I also have served as a true crime mental health expert for Investigation Discovery’s show “Crimes Gone Viral” for the past 4 years. After 2021, people were increasingly getting their information from social media platforms. To teach young doctors how to use social media, I first had to understand social media. So I did the work and began to research how to create evidence-based entertaining content (edutainment). Now the course includes how to create social media content that is evidence-based. I also recently updated the course to include how to give podcast interviews and social media “Live” interviews in addition to traditional television press interviews. I started to become active on social media so that I could teach my students. I had no idea that I would have this much personal and career success in such a short period of time. My social media reels went viral, and within 2 years I had almost 1 million followers across TikTok, Instagram, Facebook, and Threads. My social media advocacy and research led me to receiving a US House of Representatives Proclamation in June 2023. I was nominated by Congresswoman Sheila Cherfilus-McCormick in honor of Caribbean American Heritage Month and invited to Vice President Kamala Harris’s reception at the White House after my proclamation was read before Congress. Most recently I teamed up with Fides, an advocacy group within the World Health Organization, to help other health professionals around the world combat online misinformation by becoming leading voices for health care advocacy. PT: What have been some of the pros and cons of being a popular psychiatric clinician on social media? Joseph: There are so many benefits to being online because we are highly skilled and highly trained medical doctors. Becoming a content creator has allowed me to start my own mental health podcast, The Vault, and has created opportunities for me to work and partner with brands that I love. I am not an influencer, I am a “physician content creator,” and what I am doing helps to inform millions of people every day. I still have a research lab and a clinical practice where I see one patient at a time. But, using my iPhone, in 60 seconds I can create a reel that helps millions of people all over the world. Doctors belong on social media because we know how to provide information in ways that are responsible and evidence-based. If we don’t dominate the mental health social media space, then less educated, less informed, and less reputable individuals will take up the space. This is dangerous, because there is so much misinformation online. The only significant negative aspect that I have identified to being online as a professional is that you get a lot of trolls. However, the network at Fides provides guidelines and support for dealing with trolls. When I first started to ramp up my online content, some of my colleagues told me that no one would take me seriously as a researcher and psychiatrist if I became an “influencer.” My response was that I am not an influencer, I am a “physician content creator,” and what I am doing helps to inform millions of people every day. I still have a research lab and a clinical practice where I see one patient at a time. But, using my iPhone, in 60 seconds I can create a reel that helps millions of people all over the world. Some of those same colleagues who once criticized me have since apologized and have asked me for advice on how to build their online presence. I help them because I want more doctors online. We need to take up this space, because we are the most qualified to have these platforms. In addition, the social media advocacy has led me to experience so much growth in my lab; our lab space and team have since doubled. I will be offering the media course to all providers this year. Individuals can sign up for my newsletter to learn how they can attend this course virtually from anywhere in the world. PT: You mentioned your lab—Manhattan Behavioral Medicine. How did you get started in clinical research? Joseph: Before I was a resident in psychiatry, I was a resident in anesthesiology at Columbia University Medical Center. I loved intubating, doing IVs, and lumbar punctures. I loved the work, but I missed talking to patients and I missed working in teams. I was fortunate to leave my anesthesiology residency at Columbia 2 years into my training and to secure a spot in psychiatry residency at Columbia. I immediately loved psychiatry, but I missed the procedures. Clinical research in psychiatry allowed me to still use my hands and practice psychiatry. In my lab, Manhattan Behavioral Medicine, I do ECGs, blood draws, insert IVs, and administer subcutaneous injections and intranasal medications daily. We even do lumbar punctures when we test cerebrospinal fluid for dementia studies. Some of our studies require EEGs and pulmonary function tests. I love learning new skills and sharpening old skills. We recently opened a third office, where we are focusing on psychedelic studies, involving psilocybin-like compounds and ketamine. This is a very exciting time for psychiatry, and some of the drugs we investigated via clinical research are proving to be important agents in psychiatry, included the recently approved brexanolone (Zulresso) and zuranolone (Zurzuvae) for postpartum depression and xanomeline-trospium (KarXT) for schizophrenia, scheduled to be reviewed by the US Food and Drug Administration in September 2024. PT: What advice would share with clinicians who are interested in pursuing clinical research? Joseph: My advice for residents who are interested in clinical research is that they get involved in clinical research as a resident in training and then look for jobs in labs after your training so that you can work with established principal investigators. I have research mentors from my residency that I still keep in touch with. If you have completed training and you are looking to become involved in clinical research, consider taking a job at a clinical research site where you can train under a principal investigator. I love training new sub-investigators as the principal investigator of Manhattan Behavioral Medicine. PT: Among your passions is menopause advocacy. Can you tell us about your work with Let’s Talk Menopause? Joseph: I became heavily active with Let’s Talk Menopause because Black women go through menopause sooner than other women, and menopause lasts longer and with more severe symptoms than other women. I am on the board for Let’s Talk Menopause, and I am the only board member who has not gone through menopause. I am also the only Black board member. Black women have some of the scariest rates of postpartum depression, postpartum suicide, postpartum complications, perinatal death, and negative perimenopause/menopause outcomes. There is a saying in the Black community: “Black Don’t Crack.” Unfortunately, this is not true in regards to health outcomes. Black women have some of the scariest rates of postpartum depression, postpartum suicide, postpartum complications, perinatal death, and negative perimenopause/menopause outcomes. My patients who experience physical and mental health symptoms related to menopause benefit from hormone replacement therapy (HRT) and other interventions like psychotherapy and cognitive behavioral therapy for sleep. Some patients benefit from antidepressants and sleep aides. However, most people are not offered HRT, and this is problematic. According to a 2019 Mayo Clinic survey of resident physicians, only 6.8% felt adequately prepared for managing the treatment of women in menopause and only 58% of the participants had up to one lecture about menopause during residency training. This gap of knowledge in medical providers plays a large role in the lack of menopause competency in health care. In addition, many patients going through perimenopause and menopause are misdiagnosed as having major depressive disorders because of the similarity of the symptoms. They present to their doctors with cognitive concerns, identity loss, sadness, moodiness, anxiety and insomnia—symptoms that may occur in both major depressive disorder and in perimenopause. Often, these patients do not have a primary major depressive episode; they are experiencing mood symptoms related to hormonal fluctuations. The disconnect in physician knowledge is largely due to the fact that the 2002 Women’s Health Initiative study was misleading and concluded that HRT had risks that far outweighed the benefits. This statement has since been debunked, but the message that HRT was harmful was so pervasive in health care that doctors stopped prescribing it and patients have suffered as a result. Let’s Talk Menopause educates women for free via webinars, events, and social media content. In addition, advocacy is a large part of our mission and activities. We recently advocated alongside Congresswoman Yvette Clarke in front of Congress to support the MREA (Menopause Research and Equity Act).I also developed the T.I.E.S. Method to help patients identify the mental health symptoms of menopause and how to discern them from primary mental health conditions. PT: On the other end of the spectrum, much has been said about the mental health crisis in youth. As a clinical psychiatrist, what has been your experience? Joseph: I am a child psychiatrist who also treats adults, and can report that this issue is not just in children, it is happening across all ages. The post-pandemic mental health crisis seems to be worsening and people do not have access to quality mental health care. Recently I have been working with US Representative Ro Khanna and other mental health advocates to address the crisis in youth. One of the suggestions that I have made is to focus on funding mental health services and education in schools. We need to approach this from a preventative approach and teach children how to use social media responsibly, how to regulate their mood, and how to determine if relationships are harmful. We need to provide these types of workshops in the workplace for adults as well. Preventing mental health issues is where we should focus our efforts, because the reality is that it will take decades to create and disseminate new therapists and mental health professionals. The shortage of professionals is far too great, and 1 in 3 Americans lives in an area where there is a shortage of these professionals. Moreover, minority mental health is often overlooked in adults and youth. There are very few Black therapists compared with other therapists, and this creates a barrier to care. For this reason, I create social media content that directly addresses Black patient populations so that they are informed and are receiving support and resources from a cultural competency perspective. When I was a resident, I received a SAMHSA minority health grant to focus on cultural competency in the Black community, and I use what I learned during that grant period to create evidence-based content to support my community. I have also done several events with the Congressional Black Caucus around Black mental health in children and adults. PT: Another area of interest of yours is high functioning depression (HFD). Can you tell us more about this condition and what you have found in your research? Joseph: I am very excited about my research in HFD. In this post-pandemic period, we are learning about patients who have hidden conditions, like HFD which is often masked by busyness. HFD affects highly visible successful figures as well as everyday individuals. People with high functioning depression may include the chief executive officer who runs her company and masks her symptoms in light of grave financial uncertainty; or the famous sports figure who has to bring home a win for his franchise. Think of the teacher who works through lunch to grade his students’ papers on time so that they pass the state exams or the single working mom who stretches the dollar to make sure her kids are fed and gets them to school on time every day despite a lack of support. I also think that many health care professionals, specifically doctors, suffer from HFD. People with HFD push through painful situations to meet or exceed their performance expectations. Those with HFD often report symptoms of anhedonia. Although individuals with HFD have some symptoms of depression (eg, poor sleep, low energy, or self-doubt), their symptoms do not meet the DSM 5 criteria for major depressive disorder because the individuals exceed basic functioning; they push through pain and they don’t always identify as being emotionally distressed. This is why HFD often goes unnoticed by medical providers and mental health professionals; clinicians are looking for a lack or loss of functioning, and these patients do not have that. HFD is contagious, not in the way that a virus spreads, but in the way that unhealthy habits may rub off on those around us. Think about the boss who works themselves and their team to the bone, or the parent who never seems satisfied with their child’s academic progress; this can spread, if not contained. If we can contain HFD and its most insidious symptom, anhedonia, we can hopefully put an end to this epidemic and spread joy instead. My research and upcoming book on the topic shares evidence-based tools for combating symptoms of anhedonia so that life feels more meaningful and purposeful. The book and research findings are set to be released in March 2025. In the meantime, the High Functioning Blog on my website offers the high functioning depression scale and the anhedonia scale to learn more about the symptoms. I also have a free weekly newsletter that provides evidence-based tips on how to improve mental health. Note: This article originally appeared on Psychiatric Times .

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed. The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association. "Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke," lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told Medscape Medical News. "It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored." The findings were published online on June 24 in eClinicalMedicine. Significant, Chronic Health Consequences Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General's report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences. Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time. Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores. Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two timepoints, participants were divided into one of four groups: Consistently low (those who scored low on the loneliness scale at both baseline and follow-up) Remitting (those who scored high at baseline and low at follow-up) Recent onset (those who scored low at baseline and high at follow-up) Consistently high (those who scored high at both baseline and follow-up) Incident stroke was determined by participant report and medical record data. Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period. Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% CI, 1.06-1.47). Participants who reported having consistently high loneliness across both timepoints had a 56% increased risk for incident stroke vs those who did not report loneliness at both timepoints after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18). The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues. Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Soh noted. "Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient's specific personal needs is important. It's important to distinguish loneliness from social isolation," said Soh. She added that "by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness." Progressive Research Commenting on the findings for Medscape Medical News, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for "advancing the topic by looking at the chronicity aspect of loneliness." She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study timepoints. "Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don't, or can't, do this," Jones said. Chronic loneliness can cause stress, she added, "and we know that stress chemicals and hormones can be harmful to health over long durations of time." The study was funded by the National Institute on Aging. There were no conflicts of interest noted. Note: This article originally appeared on Medscape.

CASE VIGNETTE “Mr Conley” is a 62-year-old man with chronic schizophrenia. Onset was in his 20s, but he has not required inpatient psychiatric treatment in more than 20 years. He lives with his mother, but functions independently. He currently takes paliperidone palmitate 234 mg intramuscularly every 4 weeks, oral paliperidone 6 mg once daily, and quetiapine 800 mg at bedtime, which he has taken for years. He has comorbid obesity, hypertension, hyperlipidemia, and type 2 diabetes. Mr Conley has chronic auditory hallucinations and delusions of reference, particularly when watching television. His mother reports that he talks to himself and argues with family members. He also has chronic mild thought disorder. He has never attempted suicide and has no history of substance use disorder. On examination, his demeanor is pleasant and cooperative, his affect is smiling, and he does not appear to be attending to internal stimuli. Mr Conley and his mother have declined a trial of clozapine, primarily due to the need for routine blood monitoring and metabolic adverse effects. Given the potential cardiometabolic risks of polypharmacy with 2 second-generation antipsychotics, what is next? Little is known about the benefits and safety of further increasing doses vs adding another antipsychotic following nonresponse. Yet, antipsychotic polypharmacy is common, with a prevalence of up to 50%. According to the most recent American Psychiatric Association Practice Guidelines, there is no evidence that antipsychotic polypharmacy is more harmful than monotherapy. A recent meta-analysis found evidence for reduction of negative symptoms with add-on aripiprazole. There is also evidence from observational studies that antipsychotic polypharmacy may be associated with lower risk of relapse and mortality as well as treatment discontinuation. The Current Study Taipale et al5 aimed to investigate the safety of antipsychotic polypharmacy vs monotherapy, indexed by hospitalization due to physical illness or for cardiovascular reasons. They also aimed to examine the risk of relapse, indexed by psychiatric rehospitalization. The investigators used a within-individual analysis to eliminate selection bias. The investigators studied patients with schizophrenia (N = 61,889) in Finland with a diagnosis of schizophrenia while in inpatient care between 1972 and 2014 and who were alive on January 1, 1996. Follow-up started on January 1, 1996, or the date of first diagnosis, and ended either on December 31, 2017, or at the time of death (whichever occurred first). Study outcomes were nonpsychiatric hospitalization, hospitalization due to circulatory system disease, and psychiatric hospitalization. Antipsychotic dispensing data were modeled by defined daily dose (DDD) using the PRE2DUP method and were divided into periods of polypharmacy and monotherapy.6 (The Table presents DDDs.7) Mean age was 47 years, and 50% of participants were men. The mean interval since first inpatient diagnosis of schizophrenia was 9 years, and the median follow-up duration was 15 years. During follow-up in outpatient care, monotherapy was used 46%, polypharmacy 34%, and antipsychotic nonuse 20% of person-time. The risk of nonpsychiatric hospitalization was significantly lower during polypharmacy use at all total dosage categories above 1.1 DDDs/day, with differences up to 13% than during monotherapy use of the same dosage category for patients who used both monotherapy and polypharmacy. The risk of cardiovascular hospitalization was significantly lower for polypharmacy at the highest total dosage category. The pattern of findings between monotherapy and no use and polypharmacy and no use within the same individual were similar. Comparison of any polypharmacy use with any monotherapy use showed no significant difference for nonpsychiatric or cardiovascular hospitalization. Any antipsychotic polypharmacy was associated with a 6% lower risk of psychiatric hospitalization compared with monotherapy. Study Conclusions In this first study comparing antipsychotic polypharmacy vs monotherapy safety in schizophrenia, the authors found more than 40% of patients had used high-dose monotherapy and more than 50% of patients had used high-dose polypharmacy. The first nonpsychiatric hospitalization was lower for polypharmacy at total dose categories above 1.1 DDDs/day and the risk of cardiovascular hospitalization was 18% lower for polypharmacy at the highest total dosage category. Study strengths include the use of a large nationwide cohort and within-participants design. Study limitations include the absence of information on the frequency of monitoring visits, as more intensive monitoring might have contributed to the risk of hospitalization, and the assumption that time-varying covariates are multiplicatively related to the hazard. The Bottom Line Antipsychotic monotherapy is not associated with a lower risk of hospitalization for severe physical health problems compared with polypharmacy when high total dosage is assessed. Treatment guidelines should not explicitly encourage monotherapy instead of polypharmacy; the investigators argue for a more agnostic approach to this issue. Regarding Mr Conley, this study suggests that continuing both paliperidone and quetiapine is a reasonable option, although regular cardiometabolic monitoring is warranted. Note: This article originally appeared on Psychiatric Times.

We recently shared a clinical case drawn from a family medicine practice about the effect of adverse childhood experiences (ACEs) on health. The widespread epidemiology and significant health consequences require a focus on the prevention and management of ACEs. The Centers for Disease Control and Prevention published an important monograph on ACEs in 2019. Although it is evidence based, most of the interventions recommended to reduce ACEs and their sequelae are larger policy and public health efforts that go well beyond the clinician's office. Important highlights from these recommended strategies to reduce ACEs include: Strengthen economic support for families through policies such as the earned income tax credit and child tax credit. Establish routine parental work/shift times to optimize cognitive outcomes in children. Promote social norms for healthy families through public health campaigns and legislative efforts to reduce corporal punishment of children. Bystander training that targets boys and men has also proven effective in reducing sexual violence. Facilitate early in-home visitation for at-risk families as well as high-quality childcare. Employ social-emotional learning approaches for children and adolescents, which can improve aggressive or violent behavior, rates of substance use, and academic success. Connect youth to after-school programs featuring caring adults. But clinicians still play a vital role in the prevention and management of ACEs among their patients. Akin to gathering a patient's past medical history or family history is initiating universal ACE screening in practice and exploring related topics in conversation. The ACEs Aware initiative in California provides a comprehensive ACE screening clinical workflow to help implement these conversations in practice, including the assessment of associated health conditions and their appropriate clinical follow-up. While it is encouraged to universally screen patients, the key screenings to prioritize for the pediatric population are "parental depression, severe stress, unhealthy drug use, domestic violence, harsh punishment, [and] food insecurity." Moreover, a systematic review by Steen and colleagues shared insight into newer interpretations of ACE screening which relate trauma to "[...] community violence, poverty, housing instability, structural racism, environmental blight, and climate change." These exposures are now being investigated for a connection to the toxic stress response. In the long term, this genetic regulatory mechanism can be affected by "high doses of cumulative adversity experienced during critical and sensitive periods of early life development — without the buffering protections of trusted, nurturing caregivers and safe, stable environments." This micro and macro lens fosters a deeper clinician understanding of a patient's trauma origin and can better guide appropriate clinical follow-up. ACE-associated health conditions can be neurologic, endocrine, metabolic, or immune system–related. Early diagnosis and treatment of these conditions can help prevent long-term healthcare complications, costly for both patient and the healthcare system. After the initial clinical assessment, physicians can educate patients about the ways that ACE-associated health conditions are a consequence of toxic stress exposure. From there, physicians should rely on a broader integrated health team, within the health system and the community to offer clinical interventions and services to mitigate patients' toxic stress. The ACEs Aware Stress Buster wheel highlights seven targets to strategize stress regulation. This wheel can be used to identify existing protective factors for patients and track treatment progress, which may buffer the negative impact of stressors and contribute to health and resilience. The burden of universal screenings in primary care is high. Without ACE screening, however, the opportunity to address downstream health effects from toxic stress may be lost. Dubowitz and colleagues suggest ways to successfully incorporate ACE screenings in clinical workflow: Utilize technology to implement a streamlined referral processing/tracking system Train clinicians to respond competently to positive ACE screens Gather in-network and community-based resources for patients In addition, prioritize screening for families with children younger than 6 years of age to begin interventions as early as possible. Primary care clinicians have the unique opportunity to provide appropriate intervention over continual care. An intervention as simple as encouraging pediatric patient involvement in afterschool programs may mitigate toxic stress and prevent the development of an ACE-associated health condition. Note: This article originally appeared on Medscape.

PSYCHIATRIC VIEWS ON THE DAILY NEWS Living up to the social psychoexemplaries that we have discussed will inevitably fail at times. What works best then? Usually, forgiveness is suggested as it can have social benefits for both the perpetrators and victims. An example of how far forgiveness might go is in the ministry of James Lawson, Jr, who died at 95 on June 9. He was an important nonviolence strategist for the Rev. Martin Luther King, Jr. He even ministered to King’s assassin, James Earl Ray, in prison, including his 1978 prison marriage ceremony. But when is forgiveness not enough? The June 4 awarding of the Templeton Prize suggests something more. This is the lifetime achievement award, previously given to the likes of Desmond Tutu and Jane Goodall. The current recipient is the psychologist Pumla Goboda-Madikizela and her concept of “reparative quest.” Her idea came out of her experience in South Africa’s Truth and Reconciliation Commission. Later, research led her to ideas about how countries can heal after violence. She concludes that forgiveness can be insufficient. The psychological wounds and losses may be too much for closure by forgiveness. In her book she presents what might seem to be a counterintuitive concept.1 She views repair not as a 1-time act of forgiveness, but an ongoing movement up a spiritual spiral towards reconciliation via engagement and reflection. This idea evolved from her 1990s interviews with the imprisoned commander of the government-backed assassination squads, nicknamed “Prince Evil.” Seeing his vulnerability and remorse, with her empathy and psychological skills he became more of a human being rather than a monster, confirmed for her with touching his shaking hand. She also applied her concept to the infidelity of her husband when she left him. A similar process and concept, as described in the June 15 New York Times article “Jan. 6, America’s rupture and the strange, forgotten power of oblivion,” is an ancient mechanism when forgiveness seemed impossible.2 The reasoning is that the only viable alternative is to bury the wrong in oblivion, but know where it lies and the harm it caused. This is particularly challenging in a time when most everything online can be retrieved. Could that be applied to the invasion of our Capitol on January 6, 2020? There has been some movement toward individual clemency, as 12 states have passed Clean Slate laws that seal misdemeanors after a set amount of time. The worthy goal for these alternatives beyond forgiveness is to preserve the dignity of the other. Note: This article originally appeared on Psychiatric Times.

An extended-release oral tablet formulation of ketamine has shown promise for treatment-resistant depression (TRD) results of a phase 2 proof-of-concept study suggest. In the trial, twice weekly dosing of extended-release ketamine led to statistically significant and clinically meaningful improvement in depressive symptoms. Overall tolerability was "excellent," researchers reported, and common side effects commonly associated with intravenous or intranasal ketamine such as dissociation, sedation, and increased blood pressure were "minimal." "Having a tablet formulation makes it possible for patients to be safely dosed at home and would increase the number of patients who could be treated at any one time," study investigator Paul Glue, MBChB, MD, with University of Otago, Dunedin, New Zealand, told Medscape Medical News. The study was published online on June 24 in Nature Medicine. Challenging Condition TRD poses a significant challenge. "We've known for over 20 years that ketamine, a drug originally developed as an anaesthetic, is also a fast-acting antidepressant," Glue said. However, when injected or administered as a nasal spray, it has "quite marked side effects," which means it that has to be administered in a clinic, and patients need to remain in clinic for 2 hours or so after dosing, Glue added. Several small studies have shown that ketamine still works as an antidepressant when taken orally, although it still produces some dissociation. "If ketamine is formulated as an extended-release tablet (where it takes approximately 10 hours to release), most ketamine is metabolized in the liver before it can get into the circulation. It still is effective as an antidepressant because its metabolites are the main drivers of its antidepressant effects. However, the lower blood ketamine levels mean patients experience few or no side effects," said Glue. The current phase 2 trial tested the efficacy and safety of an extended-release oral ketamine tablet (R-107) in adults with TRD and Montgomery–Asberg Depression Rating Scale (MADRS) scores ≥ 20. During an open-label phase, 231 participants received 120 mg/d of R-107 for 5 days. The 168 responders, identified by MADRS scores ≤ 12 and a reduction of 50% or more, were randomly assigned to double-blind twice-weekly treatment with R-107 at doses of 30, 60, 120, or 180 mg or placebo, for a further 12 weeks. The study met its primary objective, with the 180-mg R-107 group demonstrating a significant reduction in MADRS scores compared with placebo (mean difference, -6.1; P = .019). Seventy-one percent of patients in the placebo group experienced a relapse into depression after 13 weeks compared with 43% of patients who received twice weekly oral ketamine. There were no changes in blood pressure and minimal reports of sedation and dissociation. The most common adverse events were headache, dizziness, and anxiety. More Convenient, Tolerable Several experts offered perspective on the analysis in a statement from the UK-based nonprofit Science Media Centre, which was not involved with the conduct of this study. Paul Keedwell, PhD, consultant psychiatrist and fellow of the Royal College of Psychiatrists, said that this "novel study further underlines the impressive antidepressant effect of ketamine, but in the much more convenient and acceptable form of a slow-release tablet." "In addition, the researchers demonstrated a major upside of oral ketamine — that side effects did not separate significantly from placebo," Keedwell said. He added that the study also addressed the "thorny issue of maintaining improvement after the initial response. Their results suggest that many will continue to do well with longer-term treatment, provided higher doses are used, but more research is needed with higher numbers of patients." "A potential downside of taking oral ketamine is that there are likely to be large individual differences in absorption and metabolism, so further research is needed to determine the ideal dosing regime," Keedwell noted. Also weighing in, Rupert McShane, MD, psychiatrist at the University of Oxford, United Kingdom, said that the results are "good enough to justify the larger phase 3 trials that will be necessary for a license for the 180-mg twice weekly dose." "Given the ease with which people may choose to take two tablets if they do not benefit from one tablet, regulators may be interested in the benefits and risks of higher doses," McShane commented. The study was sponsored by Douglas Pharmaceuticals, which is developing R-107. Glue is named on a patent for the extended-release ketamine formulation. A complete list of author disclosures is available with the original article. Keedwell reports no relevant conflicts of interest. McShane runs a clinic in Oxford providing ketamine as a treatment for depression, runs an academic conference about ketamine, and is leading a proposal for intravenous ketamine to be repurposed as an alternative to ECT. Note: This article originally appeared on Medscape.

Keypoint: An expert discusses this comorbidity, plus the effects of semaglutide and other GLP-1 agonists on this patient population. CLINICAL CONVERSATIONS Psychiatric Times® sat down with Elizabeth Wassenaar, MD, MS, CEDS-S, DFAPA, regional medical director of the Eating Recovery Center in Denver, Colorado, to discuss the comorbidity of eating disorders and addiction, as well as the effects of semaglutide and other GLP-1 agonists on patients with eating disorders. Psychiatric Times: How common is the comorbidity of eating disorders and addiction? How might the neurobiological pathways implicated in eating disorders intersect with those involved in addiction, and what implications does this have for the use of medications like semaglutide in managing these overlapping conditions? Elizabeth Wassenaar: The lifetime co-occurrence of eating disorders and substance use disorders was reported to be 21.9% in 2019,1 and some studies report that up to 50% of individuals with an eating disorder will abuse substances. The most commonly misused substances were tobacco, caffeine, and alcohol, and female-identifying patients with binge-purge eating disorders were most commonly affected. There are common neurobiological pathways implicated in eating disorders and substance use disorders, especially dopamine and endogenous opiate pathways. There is evidence that GLP-1 receptors also exist in reward areas of the brain and decrease rewards related to eating, including anticipation of food. GLP-1 receptor agonists' impact on dopamine may also have implications for addictive processes in the brain. PT: Research suggests that semaglutide and other GLP-1 agonists may influence appetite regulation and weight management, which are significant components of eating disorder pathology. How does the mechanism of action of these drugs impact individuals with eating disorders or addiction, considering the potential for weight loss and its effect on appetite regulation? Wassenaar: GLP-1 receptor agonists work in the brain to suppress appetite and increase feelings of fullness, which is how they act for individuals who take them to manage their type 2 diabetes. We are beginning to notice patients who are vulnerable to disordered eating and/or relapse of their eating disorder following the initiation of GLP-1 receptor agonist medications. PT: There is potentially a link between addiction-related neurobiological changes and disordered eating behaviors. How do you navigate the complexities of treating patients with both addiction and eating disorders, particularly concerning medications like semaglutide and other GLP-1s that may influence these underlying neural pathways? Wassenaar: The impact of drugs like semaglutide on mental health is not yet well understood. We do not yet understand which patients are vulnerable to the negative impact of these medications versus which patients may find mental health benefits. PT: How do you assess the risk of addiction or misuse associated with semaglutide and other GLP-1 agonists when considering their use in treatment plans for patients with eating disorders? Wassenaar: The biggest risk that I have seen is precipitating a severe eating disorder and medical complications of malnutrition. Eating disorders are one of the most fatal mental illnesses, and prescribing a medication that has the potential to trigger this is very concerning. With the opiate crisis, many practitioners thought they were being helpful and addressing pain in ways that provided better care. It was not until years and decades later we learned the tragic dark side of prescription opiate pain medications and how they could trigger the mental illness of addiction, and now we are dealing with the fallout of this prescribing practice. I worry that GLP-1 RAs could have a similar impact on eating disorders, in that we will not know the true harm for many years, and by then, countless individuals will have suffered from preventable mental illness. Dr Wassenaar is the regional medical director of the Eating Recovery Center in Denver, Colorado. Note: This article originally appeared on Psychiatric Times.