KEY POINTS Mitochondria are first responders to every change in your environment and activity. Metabolic activity makes the brain especially vulnerable to oxidative damage. Because mitochondria are involved in all you think and dream and do, any malfunction can have major effects. Your brain is a metabolically fierce organ, punching way above its weight of two pounds to consume 20 to 25 percent of the body’s fuel supply. The brain’s energy-making machinery, centered in mitochondria, is powering your ability to see this page, decode the symbols, take in the information, and maybe even store some of it in memory. Given the outsize energy demands of the brain, it is intensely populated with mitochondria, likely thousands of them per neuron. The evidence is accumulating that the many ways they function, and the many possibilities for dysfunction, are the common source of all mental health disorders. Descendants of an ancient bacterium that made its way into an equally ancient single-cell organism and worked out a cooperative living agreement—an event that likely happened two billion years ago—mitochondria are essential for producing energy, although that is by no means all they do. The energy mitochondria produce not only sustains life but enables adaptation to challenges. Mitochondria respond very quickly to your needs: They’re there for your muscles when you climb a hill or ride a bike. You can’t make a decision, answer a question, or laugh at a punch line without a blast of energy in your brain. The sensitivity of mitochondria to environmental needs makes them a critical nexus for our adaptation to the ever-changing demands of the inner and outer environment. That same sensitivity also may make them especially vulnerable to assault from an array of environmental perturbations. That vulnerability is what makes mitochondrial dysfunction a prime contender as the source of psychiatric disorders. As the descendants of once-independent organisms, mitochondria retain some autonomy; for example, they have their own DNA, something that helps mitochondria respond quickly to local energy demands without having to first consult the nuclear DNA. It also allows mitochondria to multiply on their own. Unprotected by telomeres, mitochondrial DNA is especially vulnerable to damage, which can significantly affect energy production capacity. And because of the outsize importance of mitochondria to brain activity, even small changes in mitochondrial function can have big effects. Research increasingly ties mitochondria dysfunction to a wide range of mental health conditions, from developmental disorders such as autism to psychiatric ills such as depression, bipolar disorder, and schizophrenia, to neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Mitochondria as the Master Regulator Beyond energy production, mitochondria play an essential role in the production and regulation of neurotransmitters, including serotonin, dopamine, and that all-purpose brake on neural excitability, GABA. Mitochondria are key regulators of hormones, including cortisol, essential to the stress response, and the hormones of reproduction: estrogen, testosterone, and progesterone. Mitochondria are epigenetic forces, regulating the expression of cellular genes, turning them on and off. They appear to be the ultimate responders to adversity. Everything they do has a profound impact on cognition and all other mental processes. Many roads point to mitochondria as the hub of what goes wrong in psychiatric and neurodegenerative disorders. What Goes Wrong There are many ways the function of mitochondria can be impaired. A major one is oxidative stress. ATP, derived from the breakdown of glucose, is the molecule that mitochondria produce for power, drawing on the energy contained in its chemical bonds. In the constant production of ATP, some electrons go rogue and create free radicals of oxygen, also called reactive oxygen species, (ROS). Free radicals can damage DNA, proteins, and other important cellular components. Oxidative stress describes the condition within cells when the free radicals of oxygen released in ordinary activity outnumber the antioxidants available to neutralize them and protect against the damage they can do. Because it is so metabolically active consuming so much oxygen for its constant activity, the brain is particularly susceptible to oxidative stress. In fact, the relentless accumulation of oxidative stress in all cells is why we age. Prolonged oxidative stress erodes the efficiency and activity of mitochondria, and it can damage mitochondrial genes. Another pathway to problems is poor garbage removal. All cells engage in a process of self-maintenance and self-renewal, called autophagy, by which worn-out or damaged parts are broken down and removed, and reusable elements are upcycled into new cells. Autophagy keeps cells in working order. Mitophagy is the process of upkeep and rejuvenation of mitochondria, and, given the demands on mitochondria, meticulous housekeeping is essential to the viability and function of their host brain cells. Mitochondria are normally capable of swiftly meeting energy demands by increasing their number, a process called mitochondrial biogenesis. A change in biogenesis can also impair mitochondrial function. Mitochondrial dysfunction from any cause not only leads to a decrease in ATP levels and energy production and an increase in the generation of ROS but it can also lead to inflammation. If, because of reduced mitochondrial function, defective mitochondria are not removed by mitophagy, they can release their contents, setting off inflammatory processes. Fatigue, Worry, and More When Mitochondria Malfunction The malfunction of mitochondria leads to a lack of brain energy that affects every aspect of brain operations. It is a source of fatigue. It is a cause of all degrees of cognitive sluggishness and impairment; it undermines cognitive flexibility, by which we adapt to life’s ever-changing circumstances. It impedes the most energy-intensive of operations, executive function, affecting everything from attentional focus and decision-making to impulse control, emotion regulation, and memory. Those negative thoughts and worries that play on repeat in our head? It takes lots of mental energy to keep them from taking over. Imaging studies of the brain, such as functional magnetic resonance imaging (fMRI), are essentially studies of brain metabolism. They measure changes in cerebral blood flow to meet the demands of neural activity. The last few decades have provided overwhelming evidence that in every mental disorder, there are disturbances in cerebral blood flow that show up on imaging studies; that is, there are irregularities of brain metabolism, which is centered in mitochondria. In some cases, specific brain regions are overactive, in others some regions are underactive. In all cases, mitochondria are implicated. A Link to Insulin There is more evidence that malfunctioning mitochondria cause mental illness. Metabolic disorders such as obesity and cardiac disease are extremely common in the U.S. According to the Centers for Disease Control and Prevention, more than 40 percent of U.S. adults are obese. And more than 35 percent have anxiety, depression, or both. The incidence of mental disorders among those with metabolic disorders is two to three times greater than normal. Those with mental disorders have two to three times greater chances of developing obesity and diabetes. Both kinds of disorders share a common cause: impaired mitochondrial function. Obesity, for example, is commonly accompanied by insulin resistance. Insulin is an important regulator of metabolism as well as a signaling molecule: Insulin resistance not only influences glucose metabolism and energy production but also, for example, alters dopamine dynamics, affecting reward and motivational networks in the brain, and is linked to both anxiety and depression. The evidence is mounting that mental illness is, first and foremost, a consequence of metabolic malfunction. That same knowledge is also paving the way for a whole new approach to treating mental distress. Note: This article originally appeared on Psychology Today

May is Mental Health Awareness Month, an important opportunity to recognize the needs of those with mental health issues and the ways in which those who struggle with them, both affected individuals and loved ones, can access help. Unfortunately, the mental health-related information and advice that circulates in May is often overwhelmingly focused on short-term mental health conditions like anxiety and depression, issues that today are highly treatable and far less stigmatized than they were even a few years ago. However, there is a small subset of those experiencing mental health issues that are often overlooked, even during Mental Health Awareness Month. This includes the 10 million adults in the US living with serious mental illness, meaning a mental, behavioral or emotional disorder resulting in serious functional impairment, which substantially interferes with or limits one or more major life activities. Serious mental health diagnoses include schizophrenia, bipolar disorder, major depression, acute anxiety and related illnesses. As a mental health attorney who counsels families of loved ones with serious mental health issues, I always seek to advocate for these individuals, whose needs and realities too often go unseen and/or are misunderstood. With that in mind, and in honor of Mental Health Awareness Month, I’m sharing the following 10 often-overlooked realities of those struggling with serious mental illness. These include: They often lack insight into their condition, which can make it challenging for them to accept they have a mental illness and need treatment. This reality is a major factor in the debate regarding involuntary treatment versus personal autonomy. Among those creating and reforming policies affecting those with serious mental illness, insight must always be top of mind. They are statistically more likely to be the victims of crime than perpetrators. Such a tragic reality is well worth reiterating given the enormous spotlight on occasions in which those suffering from mental illness have been involved in incidents of violence, often provoking feelings of fear and prejudice. They are overrepresented among our nation’s homeless population and among those incarcerated. Since the large-scale closing of state-run mental health facilities, a vast number of mentally ill individuals have found themselves living on the streets or in jail, where they lack needed medication and other forms of treatment, and the stability often required to make clinical progress. But serious mental illness does not equal homelessness. They are entitled to mental health care under the federal Mental Health Parity and Addiction Equity Act, which requires insurance coverage for mental health and substance use disorder treatment to be “no more restrictive” than coverage for physical health conditions. Yet despite these laws, our healthcare system is rife with persistent bias against mental health, adding challenges to individuals and families coping with diagnoses. They are further entitled to Social Security Disability Insurance (SSDI) and Supplemental Security Income (SSI) to help cover the costs of their basic needs. To qualify, a person’s mental illness must be severe enough to prevent them from performing substantial gainful activity (SGA) for at least 12 months or result in death. They are too often left out of today’s discourse concerning mental health and mental wellness. Not just during Mental Health Awareness Month but all year long, those struggling with serious mental illness simply aren’t part of the ongoing dialogue that routinely emphasizes help like self-care. They will likely require lifelong care. While there is often hope and progress for those experiencing serious mental illness, no cure exists, meaning they and their loved ones live with diagnoses all their lives. They often have family members who urgently need respite to take care of their own needs and those of other loved ones. Our country’s dire lack of mental health treatment and supportive housing has put family members on the front lines, all but forcing them to make enormous sacrifices in order to protect the health and wellness of their loved ones. They are represented across all demographics. Like all mental health issues, serious mental health illness does not discriminate, but generally first surfaces in young people ages 18-22 across racial identities, socioeconomics, geographies, etc. They, along with their families, often require legal advocacy to best ensure someone with their best interests at heart is involved in their treatment plan. The mental health legal system is notoriously complex, frequently necessitating the involvement of attorneys with real expertise in how to navigate it. While the complexities inherent in serious mental health illnesses—and the fear often surrounding them—make the conditions incredibly challenging to discuss, silence does a tremendous disservice to those who are contending with these conditions day in and day out. This May, let’s make sure our conversations include those with these hard-to-discuss, challenging issues so that they, and their families, know they aren’t alone. Note: This article originally appeared on Psychology Today

As the prevalence of mental illness continues to increase, so does the need for access to effective treatments, including psychotherapy. Since the onset of the COVID-19 pandemic, the use of online therapy (also known as virtual counseling, telepsychiatry, telepsychology, and telemental health) has greatly increased, expanding the availability of mental health services for individuals for whom in-person therapy is not available, affordable, or convenient.1 This article describes the potential benefits and drawbacks of online therapy for clinicians and patients alike. Online Therapy in the Era of COVID-19 Virtual therapy started in the 1960s to provide care to patients in rural and isolated areas. The use of telemedicine expanded exponentially during the COVID-19 pandemic, but even in the years leading up to the pandemic, the use of virtual mental health services had been increasing. A survey of state mental health facilities found that the use of telepsychiatry increased from 15% of facilities in 2010 to 29% in 2017. With the social distancing and isolation brought on by the COVID-19 pandemic, virtual mental health care became even more widely available, and psychiatric clinicians were able to treat patients remotely at a time when it was greatly needed. Psychotherapy with a licensed therapist is now commonly available via telephone or video conferencing technology. Online therapy can take place via videoconferencing on a computer, tablet, smartphone, or other device using software that is compatible with the standards of the Health Insurance Portability and Accountability Act (HIPAA). Audio-only therapy sessions over the phone may be an appropriate option for patients who do not have internet access. Several organizations offer resources to help clinicians who want to provide mental health care virtually. The American Psychological Association has established Guidelines for the Practice of Telepsychology. The American Psychiatric Association offers a Telepsychiatry Toolkit that provide extensive guidance on the technical, practical, and financial aspects of providing psychiatric care virtually. The American Telemedicine Association has similar resources available for a wide range of telehealth services. Benefits of Online Therapy Compared to in-person therapy, online therapy offers several logistical and practical advantages. The availability of virtual appointments makes it easier to treat people who live in rural or remote areas and, in general, makes it easier and faster for patients to get an appointment, which allows for more timely evaluation and treatment. Online therapy can also reduce stigma related to mental illness for individuals who are hesitant to make in-person appointments. Virtual therapy also can be cost-effective because it does not require transportation, parking, or taking additional time away from home or work to travel to appointments. For clinicians, the benefits of online therapy include increased flexibility, which might reduce burnout. Therapists can schedule to see patients in-person or virtually, and virtual appointments can be done from home.8 Increased telecommunication options have allowed mental health clinicians to expand their services, potentially increasing revenue. Virtual therapy options have also resulted in fewer “no-shows” and cancellations. Another potential benefit is that at-home health monitoring measures can be completed electronically to help inform the therapist about the patient’s progress and treatment expectations, and can allow more frequent observation. For example, patients can complete health questionnaires (such as the Patient Health Questionnaire-9) electronically before a therapy session to allow the clinician to better understand the patient’s symptoms and goals before the session begins. One concern regarding online therapy is its effectiveness vs in-person treatment. Overall, the evidence supports the efficacy of virtual mental health care. In a review of 70 studies of telemental health published from 2003 to 2013, Hilty et al found that virtual treatment was as effective as in-person care for multiple patient populations with barriers to mental health treatment. In a study of 125 adults with various eating disorders, Stieger et al reported that compared with in-person treatment, virtual treatment resulted in similar improvements in eating symptoms, weight gain (when indicated), and satisfaction with treatment. Alavi et al found that compared with in-person cognitive behavioral therapy (CBT), 12 weeks of online, therapist-supported CBT yielded comparable significant improvements in depressive symptoms and quality of life in 108 adults diagnosed with major depressive disorder. A 2022 systematic review of 12 randomized controlled trials that included 931 patients with mental health conditions (including addiction disorders, eating disorders, and childhood mental health problems) found no significant difference between virtual vs in-person psychotherapy in measures of overall improvement, function, and patient satisfaction. Some evidence suggests online therapy can be effective for patients with a wide variety psychiatric disorders, including attention-deficit/hyperactivity disorder, posttraumatic stress disorder, depression, and anxiety. The use of virtual mental health services has been associated with fewer psychiatric hospitalizations, fewer days spent in the hospital (on average), improved adherence to treatment, and improved treatment outcomes. Multiple patient populations have reported being highly satisfied with online mental health services. Drawbacks of Virtual Mental Health Care Before the COVID-19 pandemic, multiple factors limited the widespread implementation of online therapy, including insufficient clinician knowledge of and experience with providing virtual therapy, concerns for patient safety, limited reimbursement from insurance companies, and privacy/legal concerns. Clinicians, researchers, and policymakers devised effective solutions to most of these problems during the pandemic. However, some patient barriers to receiving online therapy have persisted, including limited internet access, difficulties in arranging a private space to participate in virtual therapy, and difficulties using technology due to age or disability (visual, hearing, attention deficits). In a study that conducted semi-structured interviews with 17 mental health professionals, some participants cited limited nonverbal communication and limited ability to use certain therapeutic tools, such as music or painting, as potential drawbacks of virtual therapy. Patients may have concerns for privacy, trust, and security regarding online therapy. With the increased use of telehealth, informed consent often takes place online, which raises privacy concerns in verifying a patient’s identity. Patients may participate in a virtual therapy while in a less secure/confidential location, and the session might be subject to frequent interruptions. Technical issues are also a potential barrier; approximately 30% of US adults have occasional or frequent problems connecting to the internet, and others have financial constraints to home internet or computer use. Online therapy is an emerging treatment modality, and as such, universally recognized standards for training for therapists do not yet exist. Due to the lack of standardized formal training, a therapist who works virtually might not be adequately prepared to provide a standard of care equal to that of in-person therapy. While online therapy may be equally effective as in-person therapy for many patients, certain patient populations — such as a patient who is actively suicidal, homicidal, or experiencing psychotic symptoms, or a victim of abuse who have the potential for the abuser to be present during therapy — may require in-person sessions. Summary The growing use of online therapy has greatly increased the availability of mental services, and offers potential benefits for patients as well as therapists, with some drawbacks and scenarios in which care should take place in person. The decision to provide psychotherapy virtually vs in-person generally can be made based on the patient’s preference. Clinicians must ensure their competence with providing online care, set appropriate boundaries, understand the confidentiality risks that come with online therapy, consider the possible distractions, and understand the laws and regulations for telehealth in varying jurisdictions. Resources from the American Psychiatric Association, American Psychological Association, and American Telemedicine Association outline best practices and guidelines for delivering virtual mental health services. Note: This article originally appeared on Psychiatry Advisor

May is Mental Health Awareness Month, a time to raise awareness about the impact mental health can have on a person’s overall well-being and share resources that may benefit those struggling with mental health disorders. Numerous organizations dedicated to mental health awareness and services will be participating in Mental Health Awareness Month in 2024. The National Alliance on Mental Illness (NAMI), for example, has prepared a “Take the Moment” campaign to encourage empathy, understanding, and open conversations surrounding mental health.¹ Meanwhile, Mental Health America will launch a “Where to Start” campaign that highlights how to find resources, develop coping tools, and advocate for yourself and your community.² These organizations and others will be posting on social media, offering information, and in some cases, holding events. Dialogue surrounding mental health has increased in recent decades as those in the medical field have come to understand how common mental health disorders are. According to NAMI, 22.8% of adults in the US experienced some form of mental illness in 2021, more than one fifth of the adult population.³ That same year, 5.5% of adults in the US experienced mental illness categorized as serious. Despite these figures, just 47.2% of adults experiencing mental illness in 2021 received treatment for it. Mental Health Awareness Month aims in part to reduce stigma around mental illness. The hope is to encourage treatment, both by understanding the myriad ways mental illness can affect people and the ways patients, friends, loved ones, and health care professionals can help. Doing so can not only improve patient quality of life, but health care value and total costs in the process.⁴ What is the history of Mental Health Awareness Month and what impact has it had? The History of Mental Health Awareness Month May was first designated as Mental Health Awareness Month in 1949 with the goal to increase awareness of mental illness and wellness.⁵ However, this was decades in the making – Mental Health Awareness Month was initially recognized by Mental Health America, whose first iteration was founded in 1908.⁶ Originally the Connecticut Society for Mental Hygiene, the organization was founded by Clifford Beers, an author who had written about his struggles with mental health and the problematic treatments he endured at different institutions. In 1917, the US Surgeon General asked Mental Health America to create a mental health program, the draft of which was implemented by the Army and Navy as the United States prepared to enter World War I. Mental Health America’s influence continued to grow by the 1930s, as over 3,000 people convened in Washington D.C. for the First International Congress of Mental Hygiene. President Harry Truman, in a special message to Congress in 1945, recommended a comprehensive health program and specified a need for more research and resources for mental health.⁷ This eventually culminated in Truman signing of the National Mental Health Act in 1946, which included a call for establishing a National Institute of Mental Health (NIMH).⁸ The NIMH was officially established as an institute of the National Institute of Health in 1949 – the same year as the first Mental Health Awareness Month. The Impact of Mental Health Awareness Month In the decades since the inception of Mental Health Awareness Month, research, legislation, and public awareness have accelerated the cause. Even the duration has grown; Mental Health America’s initial 1949 awareness campaign lasted only a week but eventually was expanded to the entirety of May. With the help of the NIMH, several laws were passed in the 1950s concerning mental health. The Mental Health Study Act of 1955 called for more research into mental illness, while the Health Amendments Act of 1956 gave NIMH the ability to award mental health-related project grants that got the institute more involved in community-based programs.⁸ The 1960s saw Presidents Kennedy and Johnson both call for additional research into social challenges, mental health chief among them. Notably, President Kennedy signed the Community Mental Health Centers Construction Act in 1963. Mental Health America later participated in a lawsuit that, in 1973, culminated in the release of an impounded sum of $52 million that Congress had voted on for community mental health centers.⁶ A year later, the organization successfully helped remove a question about history of mental illness from federal government employee forms. With increased funding, research, and awareness, other mental health organizations formed. In 1979, 59 family support groups in North America came together to form the National Alliance on Mental Illness.⁹ By the 1980s, NAMI was airing public service announcements across the United States.¹⁰ In the 1990s, which the US Congress declared the “Decade of the Brain,” NAMI participated in public awareness campaigns for mental health-related stigmas. The 1990s also saw the creation of a new government agency focused on mental health, the Substance Abuse and Mental Health Services Administration (SAMHSA).⁸ With NIMH focused on research, SAMHSA would focus on service availability for those struggling with addiction and mental illness. With these and other organizations dedicated to mental health research and services, researchers have been able to learn more about the effects and prevalence of mental illnesses. The World Health Organization estimated that in 2019, 970 million people around the world were living with at least one mental disorder. Research has allowed us to understand not just the prevalence, but the ways that mental health struggles affect people and those around them. Per NAMI, people with serious mental illnesses are twice as likely to develop cardiovascular and metabolic diseases compared to the general population, while people with depression have a 40% greater risk. High schoolers with significant depression symptoms are over twice as likely to drop out of school, and family caregivers to adults with mental health issues average 32 hours a week of unpaid care for their relatives. There is also an economic impact; NAMI estimates a yearly total of $193.2 billion in lost earnings for Americans on account of serious mental illness. Fostering awareness and research can potentially reduce the stigma around mental illness and receiving treatment. According to the US Centers for Disease Control and Prevention (CDC), from 2019 to 2021, the number of adults who said they received mental health treatment in the previous 12 months in the National Health Interview survey increased from 19.2% to 21.6%.¹² This increase was even more pronounced in adults aged 18 to 44, which grew from 18.5% to 23.2% in the same time period. Treatment was defined as one or both of taking prescription medication for mental health and seeking counseling or therapy for mental health. This growth in treatment is important in reducing stigma, but also speaks to how much more work there is to be done increasing awareness and access to mental health services. Note: This article originally appeared on Psychiatry Advisor

A KETAMINE JOURNAL My interest in psychedelic medicine began with a Grand Rounds at Johns Hopkins Hospital on October 7, 2019. The speaker was the late Roland Griffiths, PhD, director of the Center for Psychedelic and Consciousness Research. He presented on psilocybin as a treatment for depression, and the hospital’s department chair—Jimmy Potash, MD, MPH—interviewed a patient with a long history of major depression. The patient discussed his experience with conventional antidepressants and reported that they had helped his depression. He continued, however, to have persistent, self-deprecating thoughts that colored his mood. After participating in a clinical trial in which he received 2 doses of psilocybin, he reported that these critical thoughts were gone and he felt remarkably better. Griffiths talked about how psilocybin was administered in the trial. In 8-hour therapeutic sessions, patients were treated in rooms set up to have the ambiance of living rooms (not medical treatment rooms), with 2 “guides” attending to each patient through the experience—or “journey,” to use psychedelic lingo. In psychedelic medicine, there is a lot of attention given to the set and setting—that is, to the patient’s mindset and the physical setting. I sat in Hurd Hall that day and thought of my patients who get symptomatic relief with antidepressants, yet continue to suffer because of their harsh mental scripts. Session after session, and sometimes year after year, I listen to the same concerns from the same patients. These relentless thoughts play over and over. There are themes that I have heard from many different people over the decades: a constant fear of losing their job or an all-consuming preoccupation with what others think or expect. These patients believe they are not good enough or they do not accomplish as much as they perceive others do. The idea that one could ingest a pharmaceutical agent once or twice and skip those years of therapy sounded so appealing. I thought of the script that loops through my own head: a restlessness that I should be doing something more. It silences when I am working on a project, and it has driven me from one project to the next over years. I shrug it off with a joke and tell people that I write to stay sane and that I like new challenges. And it is not something I would casually wish away—it has taken me to some very interesting places. Between projects, however, it can be uncomfortable. Griffiths talked about how the experience of taking psilocybin is intense and profound for his research participants, many of whom have rated it as one of the most meaningful experiences of their lives. He talked about feelings of unity and connectedness. I wondered, Did you bring samples? On one hand, I was curious, and on the other, I have had many patients who have experimented with recreational psychedelic drugs—none of those patients have been magically cured of either their mood disorders or their existential struggles. I did not think it was time to shutter our practices and send the patients off to Burning Man. Nonetheless, my curiosity was piqued. After I wrote about Griffiths’ new research center at Hopkins, I read Ayelet Waldman’s memoir, A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life,1 and I wrote about microdosing and its potential role in psychiatry. I have always considered myself to be a mainstream psychiatrist. Psychedelics were not something I planned to add to my treatment arsenal, nor were they something I had ever experimented with personally, even as a student. My generation was indoctrinated with tales of the “bad trip” from which one might never emerge, and public service ads depicting the brain on drugs as a fried egg. I was educated and trained well after the US Food and Drug Administration (FDA) halted all clinical research on lysergic acid diethylamide (LSD) in 1966. Things have obviously changed in the past decade, and it seems that now you cannot pick up a newspaper or journal without seeing a study about psychedelic medicine. Access to psychedelics is still primarily limited to research studies, but that is starting to change. In traditional psychiatric practices, psychedelics present a challenge. Psilocybin journeys are long, and patients must stop their serotonergic antidepressants. Ketamine is a dissociative anesthetic that has been used off-label to treat psychiatric conditions. Although it is not technically a psychedelic (it affects different neurotransmitters than LSD, psilocybin, 3,4-methylenedioxymethamphetamine [MDMA], and other psychedelics), in sub-anesthetic doses, ketamine allows individuals to enter a non-ordinary state of consciousness similar to the states induced by classic psychedelics. It is used illegally as a recreational and club drug called Special K, and it is associated with abuse and addiction. It is probably best thought of as a “psychedelic-adjacent” substance, yet it falls under the rubric of psychedelic medicine. For psychiatry, it works as a fast and powerful antidepressant, and it works for some patients who have not responded to other treatments. Ketamine is legal, it induces short journeys that last 40 to 90 minutes, and patients do not need to stop their antidepressants to use it. The only form of ketamine that has FDA approval for the treatment of depression is intranasal esketamine (Spravato).3 Patients may get intravenous infusions of ketamine for depression off-label, and this has a defined protocol: Ketamine is given at a dose of 0.5mg/kg infused over 40 minutes, 2 or 3 times a week for a total of 6 doses. With ketamine infusions, or with Spravato, the goal is the antidepressant effect—any dissociative or psychedelic effects are unwanted adverse effects. I first heard of ketamine-assisted psychotherapy (KAP) when a colleague mentioned that he was going to KAP training. I had never heard of KAP and had to ask what the acronym stood for. I initially had no interest, but then I started seeing more and more references to it, and I realized that, although ketamine treatment is common in some parts of the country, there is very little available in Baltimore, where I practice. Most KAP is done by therapists without medical training. A physician prescribes, and the patient takes the medicine in the presence of a psychotherapist, or at home. Might there be patients who want to try ketamine with a psychiatrist present—one who could do psychotherapy and monitor for adverse reactions while keeping the patient safe? This was not an option in Baltimore in early 2023 when my interest was developing. With KAP, there is still the antidepressant effect of the medication, but the hope is to induce a dissociative/psychedelic experience. The idea is that this promotes a period of neuroplasticity—a time when old things, like negative ruminations or dysfunctional patterns, can be unlearned and new things can be learned. KAP is usually offered with sublingual or intramuscular ketamine administration, and some infusion centers are starting to couple IV administration with psychotherapy. The dose is titrated according to the patient’s weight, then to the individual response; it involves a bit of art as well as science. The psychotherapy occurs after the ketamine-induced “journey,” and in the days immediately following ketamine administration. These integration sessions help the patient understand the events of the experience within the context of their own life. KAP is done by a variety of providers in a variety of settings, including online psychotherapy with ketamine lozenges that are sent in the mail. I decided I wanted to learn how to use KAP with the hope of offering a time-limited and hopefully effective treatment for patients with unrelenting depression and psychic torment. Will it work? Am I too attached to the idea that there might be a quick fix for recalcitrant psychiatric issues? Is this too far off from my “mainstream psychiatrist” identity? Will my colleagues think I have lost my mind? Our treatments are very helpful for many patients, but for other patients, the treatments do not provide adequate relief—this might offer something new. I spent months exploring the psychedelic landscape, reading, researching, and talking to therapists who have treated patients with both ketamine infusions and KAP. I went to Colorado in August to take an intensive course on the fundamentals of KAP offered by the Psychedelic Research and Training Institute (PRATI), and I have started to use ketamine in my practice. In this series, I will be writing about my experiences—both what it entailed to get set up and what I have learned as my patients have experienced ketamine. I am a clinical psychiatrist and a writer—I am not a researcher, so please keep that in mind. I hope you will read along as I explore this innovative treatment for patients who have not responded to conventional psychiatric therapies. Note:

COMMENTARY Georgia will soon be the first state in the nation to allow independent pharmacies to sell medical marijuana products, with more than 100 pharmacies already applying to participate. This raises serious health concerns. The public should be aware that medical marijuana is not a medicine and that it differs from US Food and Drug Administration (FDA)-approved medications in several key ways. Since the 1990s, the use of medical marijuana has received significant attention and has been subject to intense debate. The use of medical marijuana was initially approved for palliative and compassionate care, primarily driven by empathy for those suffering from debilitating or terminal medical illnesses. However, the landscape has rapidly evolved, and medical marijuana now includes a wide range of claims and promoted uses. With so much circulating information available to the public, it is important to emphasize the facts about medical marijuana, especially the distinction between qualifying conditions and FDA-approved indications, its limited evidence, and the poorly regulated products available in marijuana dispensaries. The origins of medical marijuana can be traced back to the compassionate care movement of the late 20th century. It was initially promoted for individuals dealing with terminal illnesses such as cancer and AIDS and those with debilitating conditions such as late-stage multiple sclerosis. The compassionate use of medical marijuana aimed to provide relief and comfort, although not necessarily medical benefit. Compassionate care was approved for severely ill patients whose illnesses did not respond to conventional treatments as well as those who were at risk of legal jeopardy if found in possession of cannabis. One of the critical distinctions between medical marijuana and FDA-approved medications is how qualifying conditions and indications are determined. Prior to approving a new medication for treatment of a specific condition, the FDA requires rigorous research, including safety studies in both animals and humans, as well as randomized controlled clinical trials to establish that the benefits outweigh potential harms in individuals with a specific medical condition. In contrast, qualifying conditions are determined by state laws and allow patients to access medical marijuana if they have approved medical conditions. Evidence for medical marijuana use for each condition varies widely, but no state laws require the same level of rigorous research for qualifying conditions as the FDA. This explains variations in laws from one state to another, as approving or adding a qualifying condition is often a political decision rather than a scientific one. State approval of a qualifying condition does not necessarily mean that there are proven benefits for the condition, that benefits outweigh potential harms, or that a specific dose is established for each medical condition. For a list of states that have approved medical marijuana, see the Sidebar. Posttraumatic stress disorder (PTSD) is an example of a qualifying medical condition for medical marijuana in many states. Although there is some pre-clinical and anecdotal evidence that medical marijuana may have benefits for PTSD, there was no evidence of benefit in 1 randomized controlled clinical trial. Conversely, there are many reports of harmful consequences when marijuana is used to treat PTSD, including impaired attention, worsening cognition, impaired ability to operate a motor vehicle even hours after last use, development of a cannabis use disorder, psychosis, depression, anxiety, and suicide. Given these aforementioned harms and lack of evidence, the Veterans Health Administration and Department of Defense Clinical Practice Guideline on the Management of PTSD recommends against the use of cannabis products for the treatment of this disorder.3 Nonetheless, Georgia and other states have included PTSD in the growing list of medical conditions that can qualify an individual to obtain a medical marijuana card. Another difference between medical marijuana products and FDA-approved medications is the way they are prescribed/recommended and consumed. When prescribing FDA-approved medications, clinicians prescribe a specific dose and duration of treatment according to the package insert, which is established by randomized controlled clinical trials. However, there have been no randomized controlled clinical trials to establish the safety and efficacy of commercial marijuana products, nor the optimal dose ranges. And dose matters. For example, frequent use of high-potency cannabis can cause severe intractable vomiting known as cannabis hyperemesis syndrome, which is only relieved by stopping cannabis use. For medical marijuana, the specific cannabis product and amount are often determined by consumers or at the discretion of the marijuana retailer. Medical marijuana lacks strong scientific evidence to support many of its purported benefits. Much of the evidence comes from anecdotal reports, small-scale uncontrolled studies, and patient accounts. These sources do not meet the standards of rigorous randomized placebo-controlled trials, which is the gold standard for medical evidence. Although more quality research is needed, there are several barriers to achieving this. First, despite state laws allowing for its sale, marijuana remains a Schedule I controlled substance under federal law in the United States, which some argue hinders research efforts. Additionally, conducting rigorous controlled clinical trials on raw marijuana plants is nearly impossible due to the inherent variability in the concentration of active ingredients and the composition of other chemical compounds. Manufacturing and quality control standards for FDA-approved medications and medical marijuana products also differ greatly. FDA-approved medications are manufactured with rigorous standards for dose and purity. For example, the FDA requires that each tablet contains the same dose of medication that was shown to be effective in the research studies that led to its approval and that no other toxic chemicals were introduced in the manufacturing process. Medical marijuana products, on the other hand, lack such quality control. Thus, there are considerable variations in the composition and potency of medical marijuana products. Often, the content on the product label does not match the actual tetrahydrocannabinol (THC) or cannabidiol (CBD) content on the label, making it difficult to determine appropriate dosages and assess potential risks versus benefits. Furthermore, the manufacturing process can introduce toxic chemical compounds including pesticides and organic solvents such as butane. Allowing medical marijuana products to be sold in pharmacies will lead to false beliefs in their benefit and create more confusion for consumers. Currently, there are only 4 FDA-approved cannabis-derived medications: Epidiolex® (cannabidiol) for 2 rare forms of epilepsy, Marinol® and Syndros® (both dronabinol) for nausea and vomiting caused by HIV or chemotherapy, and Cesamet® (nabilone) for nausea and vomiting from chemotherapy. These FDA-approved medications are legal and available nationwide by prescription from a medical provider, but they are not sold through state medical marijuana programs. In contrast, cannabis products available in dispensaries (and soon in Georgia pharmacies) have not met the FDA’s stringent standards for safety and efficacy upheld for prescribed medications. For FDA-approved, cannabis-based medications, the package inserts also warn of potential risks even when the medications are used at recommended doses and durations. Clinicians are advised to prescribe the medications at the lowest effective dose for the shortest possible duration to mitigate the risk of adverse effects. These package inserts advise patients against driving a motor vehicle while using the product due to impairments in coordination and cognition that may last hours after they are taken. In contrast, most cannabis products sold in dispensaries lack any warnings about potential adverse effects, but not because these products are safer than FDA-approved medications. Studies suggest that frequent use of cannabis—either recreational or medicinal—may lead to the development of a cannabis use disorder, which can negatively impact health. This is of particular concern, as the THC content of cannabis products and the frequency of use has increased in recent years. Whereas 10 years ago, the risk of developing a cannabis use disorder among those who used cannabis was about 1 in 10, more recent data finds the risk to be about 1 in 3.4 This risk is even higher for individuals with a history of another substance use disorder or a predisposition to addiction due to family history or the presence of another mental illness. Studies also show that cannabis use can cause or exacerbate mental health conditions such as depression, bipolar disorder, suicide, and psychosis.2 For individuals who already have or are predisposed to these conditions, the use of medical marijuana should be approached with even more caution, if at all. In summary, as we start to see state laws allow marijuana to be sold in pharmacies, we need to take a step back and question a decision that will have a major impact on public health. Taking into account the historical context, differences between qualifying conditions and FDA-approved indications, limited research evidence, and the unregulated nature of products in dispensaries, it is important to educate the public about the distinction between medical marijuana and medicine. There is an urgent need to emphasize quality research to assess the potential benefits and risks associated with marijuana use. In the absence of randomized placebo-controlled clinical trials, health care providers and patients must approach medical marijuana with caution, weighing the potential benefits against the limited evidence and regulatory uncertainties. Note: This article originally appeared on Psychiatric Times

CATEGORY 1 CME Premiere Date: April 20, 2024 Expiration Date: October 20, 2025 This activity offers CE credits for: 1. Physicians (CME) 2. Other All other clinicians either will receive a CME Attendance Certificate or may choose any of the types of CE credit being offered. ACTIVITY GOAL To discuss and describe the epidemiology, assessment, and evidence-based treatment of insomnia in older adults. LEARNING OBJECTIVES 1. Discuss the epidemiology and assessment of insomnia in older adults. 2. Enumerate the evidence-based treatments for insomnia in older adults. TARGET AUDIENCE This accredited continuing education (CE) activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders. 'ACCREDITATION/CREDIT DESIGNATION/FINANCIAL SUPPORT This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Physicians’ Education Resource,® LLC, and Psychiatric Times.® Physicians’ Education Resource, LLC, is accredited by the ACCME to provide continuing medical education for physicians. Physicians’ Education Resource, LLC, designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits.™ Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity is funded entirely by Physicians’ Education Resource, LLC. No commercial support was received. OFF-LABEL DISCLOSURE/DISCLAIMER This accredited CE activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this accredited CE activity is for continuing medical education purposes only and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic or treatment options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of Physicians’ Education Resource, LLC. FACULTY, STAFF, AND PLANNERS’ DISCLOSURES AND CONFLICT OF INTEREST (COI) MITIGATION None of the staff of Physicians’ Education Resource, LLC, or Psychiatric Times or the planners or the authors of this educational activity have relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, reselling, or distributing health care products used by or on patients. For content-related questions, email us at PTEditor@mmhgroup.com; for questions concerning the accreditation of this CME activity or how to claim credit, please contact info@gotoper.com and include Assessing and Treating Insomnia in Older Adults in the subject line. HOW TO CLAIM CREDIT Once you have read the article, please use the following URL to evaluate and request credit: https://education.gotoper.com/activity/ptcme24apr. If you do not already have an account with PER,® you will be prompted to create one. You must have an account to evaluate and request credit for this activity. In humans, sleep is divided into nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep.1 The non-REM sleep consists of 3 stages (N1-N3), with N1 and N2 being considered lighter stages of sleep, and N3 being considered as deep sleep. In healthy adults, sleep starts with NREM sleep and is then followed shortly by REM sleep.2 During a normal night’s sleep, there are 4 to 5 alterations between NREM and REM sleep. Electroencephalogram (EEG) recordings show increasing voltage and decreasing frequency as NREM sleep progresses into deeper stages. The heart rate and blood pressure also decline during NREM sleep, whereas gastrointestinal motility and parasympathetic activities increase. In REM sleep, there are bursts of rapid eye movements, but there is significant loss of muscle tone. Changes in sleep that are associated with normal aging include advances in sleep timing, a decrease in nocturnal sleep time, a decrease in sleep efficiency, an increase in the frequency of daytime naps, an increase in sleep latency, an increase in nocturnal awakenings, an increase in stages N1 and N2 of NREM sleep, a decrease in stage N3 of NREM sleep, a decrease in the percentage of REM sleep, and a decrease in total sleep time (TST).3,4 The TST decreases until about 60 years of age and then stabilizes in the later decades of life.3,5 Additionally, the circadian system and sleep homeostasis become less robust, and the pattern of sleep-related hormone secretions change with normal aging. Table 13,4 lists the sleep architectural changes associated with normal aging. The sleep architectural changes associated with normal aging occur due to the decline in efficiency of the circadian internal clock.2,3 Additionally, there is reduction in the amplitude of circadian oscillation along with a decline in levels of melatonin. Aging also results in the reduction of the efficiency of the suprachiasmatic nucleus in the hypothalamus (main central clock), which negatively affects the day/night synchronization of the peripheral cellular clocks, causing significant changes in endocrine and metabolic pathways, the sleep-wake cycle, body temperature, motor activity, and behaviors. Furthermore, the decrease in the delta power and associated increase in beta wave power noted on EEGs that are caused by age-associated atrophy of the brain and cortical thinning also contribute to the sleep architectural changes associated with normal aging. The word insomnia is derived from the French word insomnie, which refers to difficulties with sleep.6,7 According to the DSM-5-TR, insomnia becomes a disorder when the individual presents with a predominant complaint of dissatisfaction with sleep quantity or quality and it is associated with (≥ 1) of the following symptoms: (1) difficulty initiating sleep, (2) difficulty maintaining sleep that is characterized by frequent awakenings or problems with returning to sleep after awakenings, and (3) early-morning awakening and inability to return to sleep.8 The sleep disturbance also causes clinically significant distress or impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning. Furthermore, the sleep difficulties occur for at least 3 nights per week and last for at least 3 months. These sleep difficulties also occur despite adequate opportunities for sleeping, and they are not better explained by, and do not occur exclusively due to, another sleep-wake disorder. The insomnia is also not attributable to the physiological effects of a medication or substance abuse and is not adequately explained by the presence of mental or medical conditions. The DSM-5-TR specifies that insomnia can occur with non-sleep disorder mental comorbidity, including substance use disorders; with other medical comorbidity; or with other sleep disorders. Insomnia can be episodic if symptoms last at least 1 month, but less than 3 months; persistent, if symptoms last ≥ 3 months; and recurrent if there are ≥ 2 episodes within a 1-year period. Epidemiology Among older adults, the prevalence of insomnia symptoms ranges from 30% to 48%.9 Most of these individuals present with sleep maintenance symptoms (50%-70%), followed by difficulty initiating sleep (35%-60%), and nonrestorative sleep (20%-25%). The annual incidence of insomnia among older adults is approximately 5%, with approximately half of these individuals reporting a remission in symptoms at 3-year follow-up.10 The prevalence of insomnia disorder among older adults ranges from 12% to 20%. Evidence indicates that insomnia is more common among older adults with lower education levels, those at lower income levels, those who are in low-ranking positions, those with limited social contact with children and friends, those who are less spiritual, those who have less financial support, those who lack close family and friends, and those with less desirable living situations. One study found that African American women had a greater incidence of insomnia compared with African American men (19% vs 12%, P < 0.01) and compared with White men and women (both 14%, P <0 .01).10 Women were also less likely than men to report a remission in symptoms of insomnia at follow-up (42% vs 64%, P < 0.01). Among both races, the presence of depressed mood was a risk factor for the incidence of insomnia, and the absence of depressed mood was a predictor of remission of symptoms. A retrospective database review found that female sex and the presence of dementia, depression, anxiety, chronic pain disorders, or atrial fibrillation are associated with thdevelopment of insomnia in older adults. Insomnia is also more common among older adults who have heart disease, stroke, and diabetes. Additional risk factors for the development of insomnia are the presence of chronic diseases, the use of prescribed sedatives, widowhood, depressed mood, physical disability, and poor perceived health. The use of stimulants, nasal decongestants, steroids, antidepressants, antihypertensives, and analgesics also increase the risk of developing insomnia in older adults. Environmental risk factors for insomnia among older adults include excess noise, hot or cold temperatures, moving to a new place of living, and institutionalization. Social and behavioral factors include irregular sleep schedule, caregiving, retirement and other lifestyle changes, and bereavement. A systematic review found that among older adults, factors that were most consistently identified as risks for future sleep disturbances were female gender, depressed mood, and physical illness. The investigators found less robust evidence for the following as risks for future sleep disturbances: lower physical activity levels, African American race, lower economic status, previous manual occupation, widowhood, marital quality, loneliness, perceived stress, preclinical dementia, long-term benzodiazepine and sedative use, low testosterone levels, and inflammatory markers. Consequences Insomnia among older adults is associated with the development of depressive symptoms, especially poor sleep quality and difficulty initiating and maintaining sleep.15 Insomnia is also associated with the development of suicidal ideation. The risks for developing hypertension, myocardial infarction, and cerebrovascular events are greater among individuals with insomnia. Insomnia also increases the risk for metabolic syndrome and diabetes. Older men with insomnia are at greater risk of developing prostate cancer. One meta-analysis indicated that insomnia among older adults increases the risk for dementia (relative risk [RR]= 1.53). Insomnia also worsens quality of life and adds to the direct and indirect cost of caring for these individuals. Assessment When evaluating symptoms of insomnia among older adults, it is essential to obtain a thorough clinical history from the individual and their family members who are aware of the person’s sleep habits.13 This history should assess the nature, the frequency, the progression, and the total duration of symptoms of insomnia. Conditions prior to sleep; sleep-wake patterns; symptoms of other sleep disorders, such as sleep apnea and restless leg syndrome; and the daytime consequences of insomnia should also be evaluated. Furthermore, the predisposing, precipitating, and perpetuating factors for insomnia including behavioral and environmental factors, comorbid psychiatric disorders, substance use disorders, medical conditions, and intake of medications that can cause or worsen insomnia should be also be assessed. A thorough history should also assess the prior treatments for insomnia and the individual’s response to these treatments. Sleep dairies that follow an individual’s sleeping and wakefulness patterns, and sleep questionnaires like the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity. Index (ISI), can assist with the identification and a diagnosis of insomnia in older adults. Polysomnography (PSG) is not indicated for the routine assessment of insomnia in older adults.19 PSG should only be considered when sleep apnea or a movement disorder is suspected, or when the individual has failed behavioral or pharmacologic treatments for insomnia. Figure 1 discusses the pathway for assessing insomnia in older adults. Management Available evidence indicates that both nonpharmacological and pharmacological strategies have shown benefit in the management of insomnia among older adults. The choice of treatment often depends on multiple factors including the duration and severity of symptoms, comorbidities, the individual’s motivation for accepting nonpharmacological (behavioral) treatments, and the individual’s risk for developing adverse effects from medications. Irrespective of the type of treatment that is chosen, the main goals of treatment are to improve the quality and quantity of sleep and to minimize daytime impairments due to insomnia. Additionally, the treatment should improve any psychological distress caused by insomnia. In most cases, nonpharmacological interventions should be considered as first-line treatments for insomnia in older adults.9 Nonpharmacological and pharmacological treatments should be combined when either of the treatments has not produced the desired results. Nonpharmacological Treatments Cognitive Behavioral Therapy for Insomnia (CBT-I) CBT-I is a highly effective nonpharmacological treatment for insomnia.22 CBT-I appears to have the equivalent efficacy to hypnotic agents and has no known adverse effects. The long-term improvements from CBT-I are thought to occur due to the individual with insomnia learning how to engage and promote their body’s natural sleep mechanisms. Sleep consolidation, stimulus control, cognitive restructuring, sleep hygiene, and relaxation techniques are the 5 key components of CBT-I. The treatment can be delivered by a trained therapist via a self-guided method, or via fully automated online programs including SHUTi and Sleepio, among others.23 One meta-analysis of 20 studies that included individuals with a mean age of 56 years found that CBT-I improved sleep-onset latency (SOL) by 19.3 minutes, wake-after-sleep onset (WASO) by 26 minutes, TST by 7.61 minutes, and sleep efficiency (SE) by 9.91%. The investigators also noted sustained improvements at later time points. The American College of Physicians (ACP) recommends that all adults with chronic insomnia should receive CBT-I as the initial treatment.15 One recent meta-analysis that included data from 14 studies found that CBT-I improved SE (8.36%, P < 0.00001), SOL (-9.29 minutes, P <0 .0001), WASO (-23.44 minutes, P <0 .00001), and TST (-12.35, P = 0.007) in older adults. When CBT-I alone is not successful in managing insomnia, the ACP recommends using a shared decision-making approach by clinicians that includes a discussion of the benefits, harms, and costs of short-term use of medications in order to decide whether to add pharmacotherapy. Brief Behavioral Treatment for Insomnia (BBTI) BBTI emphasizes the behavioral elements of insomnia treatment in lieu of the cognitive components of CBT-I.23 BBTI includes 4 main interventions: reduced time in bed to match the actual sleep duration; getting up at the same time every day, irrespective of the duration of sleep; going to bed only when sleepy; and only staying in bed when asleep. BBTI is delivered in a single initial session that is then followed by 2 to 3 brief follow-up visits either in person or via telephone. BBTI has been found to be beneficial among older adults (mean age 71.7 years) with chronic insomnia (remission or response vs partial response or nonresponse rates, P < 0.001), when compared with controls.27 BBTI also produced better results in self-reported sleep and health assessments (P< 0.001), sleep diaries (P < 0.001), and actigraphy (P < 0.001), with improvements being maintained at 6 months. The number needed to treat (NNT) was 2.4. There were no differential effects noted based on hypnotic or antidepressant use, sleep apnea diagnosis, or the source of recruitment. Sleep Restriction Therapy (SRT) SRT improves sleep drive and consolidates sleep by making the individual’s time in bed equivalent to their total sleep duration.28 The total sleep duration is assessed with daily sleep diaries. In a randomized controlled trial (RCT) of older adults (mean age 68.9 years), individuals receiving SRT had significantly lower SOL (effect size = 1.11, P ≤ 0.003) and WASO (effect size = 1.19, P ≤ 0.031), and higher SE (effect size = 1.74, P ≤ 0.007) than controls. Results post treatment at 3 months and 1 year showed that TST for the SRT increased from post treatment to 3 months (P = 0.04). Time in bed also changed over time (P < 0.0001). Additionally, insomnia severity improved post treatment among the SRT group (effect size = 1.18, P ≤ 0.0001). Treatment response was achieved in 50% of SRT participants (P = 0.001), with remission observed in 22.73% of the participants (P = 0.0001). Stimulus Control Therapy (SCT) SCT consists of a set of instructions designed to restore the association between bed/bedroom and sleep.28 SCT also establishes a consistent wake time. The instructions for SCT are to go to bed only when sleepy, to get out of bed when unable to sleep, to use the bed/bedroom for sleep and sex only, to wake up at the same time every morning, and to refrain from daytime napping. In an RCT of older adults (mean age 68.9 years), Epstein, et al, found that individuals who received SCT had significantly lower SOL (effect size = 1.44, P ≤ 0.01), WASO (effect size = 1.04, P ≤ 0.01), and TST (effect size = 1.08, P ≤ 0.01) than controls.29 Treatment response was achieved in 56.6% of SCT participants (P = 0.001), with remission observed in 29.55% of the participants (P = 0.0001). Relaxation Therapy (RT) RT includes structured techniques that are designed to reduce somatic tension (abdominal breathing, progressive muscle relaxation, etc) and cognitive arousal (guided imagery training and meditation) that may perpetuate sleep difficulties.28 In an RCT, Lichstein, et al, found that among older adults (mean age 68.11 years), RT improved SOL (effect size = 0.18 and 0.40, respectively), WASO (effect size = 0.26 and 16, respectively), TST (effect size = 0.28 and 0.43, respectively), and SE (effect size = 0.16 and 0.29, respectively), when compared with placebo both post treatment and at follow-up. Summary of Cognitive and Behavioral Interventions The American Academy of Sleep Medicine (AASM) systematic review, meta-analysis, and GRADE assessment found that there is a significant amount of evidence to support the use of behavioral and psychological treatments—especially CBT-I—among adults with insomnia.28 However, this report also concluded that there are challenges for the delivery of these interventions—hence, there is a need to identify means for the optimal delivery of these treatments. One RCT also found that SCT, SRT, and multicomponent intervention (MCI) are equally efficacious and produce sustainable treatment gains among older adults with chronic primary insomnia. A recent systematic review that evaluated the effectiveness of the behavioral components of CBT for insomnia in older adults included data from 15 studies.31 Among these, 3 studies focused on stimulus control (SC), 4 evaluated sleep restriction (SR), and 8 used MCI that contained both SC and SR. The investigators concluded that both SC and SR were effective in improving subjectively measured aspects of sleep, which was maintained at 3-month follow-up. Additionally, no significant differences were noted between these 2 treatments. However, effect sizes in studies that solely used SC or SR were smaller and more heterogenous than studies that included multicomponent interventions (effect size = 0.55). Hence, in clinical populations where CBT-I may be cognitively difficult, treatments with MCI that combine both SC and SR can be used successfully. Pharmacotherapy Although CBT-I is the recommended as first-line treatment for insomnia, many individuals will be offered and/or want pharmacotherapy for the management of their insomnia.32 The reasons for offering pharmacotherapy for insomnia include the lack of availability of clinicians who can provide CBT-I, the ease of availability of pharmacotherapy, and the reduced time commitment that is required for pharmacotherapy, when compared with behavioral interventions. Pharmacotherapy is also used when there is the need for a faster treatment response. There are some general considerations that should be followed when prescribing medications for insomnia in older adults. Multimorbidity and polypharmacy are major concerns when prescribing any medications for older adults, as 51% of older adults have multimorbidity, and 32% have encountered polypharmacy. These issues result in greater risk for new hospitalizations, falls, decline in both physical and cognitive functions, and death among older adults. Additionally, there are significant pharmacokinetic and pharmacodynamic changes that occur with age that should be taken into account when prescribing medications to any older adult. These changes result in reduced metabolism and excretion of medications, which can cause toxic accumulation of drugs, even at approved dosage ranges. Furthermore, polypharmacy can result in dangerous drug-drug interactions that can result in catastrophic outcomes among older individuals. As per the American Geriatrics Society (AGS) 2023 updated AGS Beers Criteria,® most of the medications used in treating insomnia are considered potentially inappropriate for use in older adults and should either be avoided or be used with extreme caution.38 Hence, medications for insomnia should only be used following a careful risk/benefit analysis and as short-term treatments. Additionally, medications should be considered as adjunct to nonpharmacological interventions.33 When medications are prescribed to older adults with insomnia, they should be carefully monitored for both efficacy and adverse effects. Once the insomnia is under better control, a taper and discontinuation of the medication should be attempted. Intermittent use of medications is acceptable, as long as the individual is also pursuing CBT-I. Four medication classes are approved by the FDA for the treatment of insomnia among adults. These include the benzodiazepine receptor agonists (benzodiazepines and nonbenzodiazepines, or Z-drugs), dual orexin receptor agonists (DORAs), selective histamine antagonists, and selective melatonin receptor agonists. Tricyclic antidepressants like amitriptyline and nortriptyline have also been used to treat insomnia among older adults, but they should be either avoided or used cautiously due to their serious adverse effects, including anticholinergic effects and cardiotoxicity. 34,39-41 In addition, these medications should only be used by individuals who have insomnia and comorbid depression, fibromyalgia, or neuropathic pain. The use of anticonvulsants like gabapentin or pregabalin should be restricted to individuals with insomnia and comorbid seizure disorder, fibromyalgia, restless leg syndrome, or neuropathic pain. Similarly, the use of antipsychotic medications like olanzapine and quetiapine should be restricted to only individuals who have insomnia and comorbid schizophrenia spectrum disorders or mood disorders. Antihistamines like diphenhydramine and hydroxyzine have also been used for the treatment of insomnia in older adults, but their routine use is not recommended due to their severe adverse effect profile, which includes anticholinergic effects. Tryptophan and valerian have also been used to treat insomnia in older adults, but the evidence for their efficacy is lacking at this time. In a meta-analysis published in The Lancet, the investigators included data from 154 RCTs in adults.42 They found that for the acute treatment of insomnia, benzodiazepines, eszopiclone, lemborexant, zolpidem, and zopiclone were more efficacious than placebo (effect size = 0.36 to 0.83). Additionally, benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (effect size = 0.27 to 0.71). The investigators also found that intermediate-acting benzodiazepines [odds ratio (OR) = 0.72], long-acting benzodiazepines (OR = 0.70), and eszopiclone (OR = 0.71) had fewer discontinuations due to any cause than did ramelteon. Zopiclone (OR = 2.00) and zolpidem (OR = 1.79) caused more dropouts due to adverse events than did placebo. Zopiclone caused more dropouts than eszopiclone (OR = 1.82) and suvorexant (OR = 3.13). For the long-term treatment of insomnia, eszopiclone (effect size = 0.63) and lemborexant (effect size = 0.41) were more effective than placebo. Eszopiclone was more effective than ramelteon (effect size = 0.63) and zolpidem (effect size = 0.60). When compared with ramelteon, eszopiclone (OR = 0.43) and zolpidem (OR = 0.43) had lower rates of all-cause discontinuations. When compared with placebo, zolpidem was associated with a higher number of dropouts due to adverse effects (OR = 2.00). Concluding Thoughts Insomnia is not uncommon among older adults. It is associated with significant negative outcomes in these individuals including a decline in physical, mental, and cognitive health. The etiologies for insomnia in older adults are often multifactorial due to the complex interactions between various biological, psychological, social, and environmental factors. Assessment of insomnia in older adults should involve a thorough history including an evaluation of all possible risk factors. Sleep diaries and sleep questionnaires can assist with the identification and diagnosis of insomnia in older adults. PSG is only indicated when sleep apnea or movement disorders are suspected, or when the individual has failed behavioral or pharmacologic treatments for insomnia. CBT-I is the recommended as first-line treatment for insomnia in older adults. However, BBTI, SRT, SCT, and RT have also been found to be effective in the treatment of insomnia in this patient population. Pharmacotherapy is used in situations where there is a lack of availability of clinicians who can provide CBT-I and in situations where there is the need for a faster treatment response. The 4 medication classes that are approved by the FDA for the treatment of insomnia among adults are the benzodiazepine receptor agonists (including the Z-drugs), DORAs, selective histamine antagonists, and selective melatonin receptor agonists. Although not FDA approved, certain anxiolytics, anticonvulsants, antidepressants, antipsychotics, nutritional products, and herbs are also used to treat insomnia in older adults. Medications should be used cautiously in older adults with insomnia due to their risk for serious adverse effects and drug-drug interactions. Additionally, medications should be used at the lowest effective doses and for the shortest possible duration and as adjuncts to nonpharmacological treatments. Note: This article originally appeared on Psychiatric Times

Keypoint: Higher IV ketamine doses do not outperform standard doses for treatment resistant depression. Intravenous (IV) ketamine for treatment resistant depression is effective at lower doses of 0.2 to 0.5 mg/kg, without significantly increased benefit at 1 mg/kg. Conversely, the efficacy of intranasal (IN) esketamine for reducing depressive symptoms increases with doses above 28 mg, reaching optimal response between 56 and 84 mg. These findings from a systematic review and meta-analysis were published in the Journal of Affective Disorders. Both IV ketamine and IN esketamine have been associated with rapid antidepressant effects among patients with treatment resistant depression. However, optimal dose ranges have not yet been defined for either treatment. To address this knowledge gap, investigators from the Mayo Clinic in Rochester, Minnesota searched publication databases through June 2023 for randomized controlled trials (RCTs) that evaluated esketamine or ketamine for treatment resistant depression. The investigators categorized IV ketamine doses as low dose (£0.2 mg/kg), standard dose (>0.2 to 0.5 mg/kg), and high dose (>0.5 mg/kg) for analyses. The efficacy outcomes were changes in depressive symptoms 24 hours after IV ketamine and 28 days following IN esketamine, respectively. For IV ketamine, the investigators included 5 RCTs, for a pooled sample size of 262 participants (IV ketamine: n=196; control: n=66). The doses of IV ketamine ranged from 0.1mg/kg to 1 mg/kg. For IN esketamine, 7 RCTs were included with a total study population of 1372 participants (IN esketamine: n=718; control: n=655), and doses ranged from 28 mg to 84 mg. Relative to control, the mean effect size of IV ketamine was 1.58 (95% CI, 0.94-2.22; I2, 78%; P <.001) and IN esketamine was 0.31 (95% CI, 0.17-0.44; I2, 22%; P <.001). For IV ketamine, low (Hedges g, 1.2; P =.02), standard (Hedges g, 1.54; P =.01), and high (Hedges g, 2.5; P =.003) doses were all superior to control. The investigators did not observe significant differences in overall effect at different dose ranges. These findings suggest that high IV ketamine doses are not more efficacious than standard doses. When stratified by IN esketamine dose, the investigators found that 28 mg did not outperform the control conditions (Hedges g, 0.26; P =.23). However, a dose of 56 mg (Hedges g, 0.37; P =.03), flexible dosing between 56 and 84 mg (Hedges g, 0.27; P =.001), and a dose of 84 mg (Hedges g, 0.45; P =.03) were all more effective than control. The most common side effects for both treatments were dizziness, headache, dissociative symptoms, and dysgeusia. In addition, transient elevation of blood pressure tended to occur at higher doses. The investigators concluded, “The available data does not provide sufficient evidence that the higher IV ketamine doses (>0.5 mg/kg) are more efficacious than standard dose (0.5 mg/kg).” The major limitation of this analysis was the small sample sizes for each dose group. Note: This article originally appeared on Psychiatry Advisor

Keypoint: The total number of psychotropic medications administered during pediatric emergency department encounters rose by 624% from 2013 to 2022. The use of psychotropic medications during pediatric mental and behavioral health (MBH) encounters in emergency departments has increased from 2013 to 2022, according to study results published in Pediatrics. However, psychotropic medication use significantly varies across hospitals, indicating a need for standardization in emergency department management to improve quality of care. Although previous studies have shown that psychotropic medication is frequently used during MBH visits in pediatric emergency departments, there is a lack of information regarding potential variability in psychotropic medication administration at the hospital level. Therefore, researchers conducted a retrospective cross-sectional study to evaluate changes in psychotropic medication use over time across pediatric hospitals in the United States. The researchers used data from 2013 to 2022 in the Pediatric Health Information System to identify MBH encounters (validated using International Classification of Disease [ICD] codes) among patients aged 3 to 21 years in emergency departments across the US. Eligible psychotropic medications included psychotherapeutics (anxiolytics, antidepressants, antipsychotics), stimulants, anticonvulsants, antihistamines, and antihypertensives. Over the study period, there were 670,911 emergency department encounters involving youth with primary MBH diagnoses and 12.3% of these encounters involved psychotropic medication administration. The pediatric patients in these encounters were mostly girls (57.5%), White (59.2%), non-Hispanic (75.8%), publicly insured (53.3%), and aged 13 to 17 (62.8%) years. The most common MBH diagnoses were depressive disorders (24.9%), suicide/self-injury (22.9%), and disruptive behavior disorders (9.4%). However, the highest frequency of psychotropic medication administration was observed among individuals with intellectual disabilities (25.4%) and autism spectrum disorders (25.3%). The researchers found that psychotropic medication administration during emergency department visits increased from 7.9% in 2013 to 16.3% in 2022 among pediatric patients, and the odds of psychotropic medication administration increased each year (odds ratio [OR], 1.09; 95% CI, 1.05-1.13). The total number of psychotropic medications administered during emergency department MBH encounters rose by 624% from 2013 (n=6652) to 2022 (n=48,174), with a yearly incidence rate ratio of 1.11 (95% CI, 1.09-1.15). The researchers noted significant increases in psychotropic medication administration across all age groups for most psychotropic medication categories, except anxiolytics. However, the researchers observed significant variability in the percentage of MBH encounters involving psychotropic medication across hospitals, ranging from 4.2% to 23.1% (P <.001). Similarly, the total number of psychotropic medications administered varied from 81 per 1000 MBH encounters to 792 per 1000 MBH encounters (P <.001). “Across the study period, the proportion of MBH encounters with at least 1 psychotropic medication administered doubled, and the total number of psychotropic medications administered in the ED increased nearly sevenfold,” the researchers noted. “Inconsistent practice patterns indicate that opportunities are available to standardize ED management of pediatric MBH conditions to enhance quality of care.” Study limitations include a lack of data confirming whether medications were successfully administered and potential misclassification of diagnoses and demographic characteristics. Note: This article originally appeared on Psychiatry Advisor

TOPLINE: Most children and adolescents with chronic skin disorders may experience stigma, which is strongly associated with reduced quality of life (QOL) and childhood depression. METHODOLOGY: Stigmatization has been addressed for several chronic medical conditions, such as HIV/AIDS, obesity, and mental illness; however, it has received limited attention in children living with chronic skin disorders. This cross-sectional, single-visit study examined the prevalence of stigma, its dependence on disease visibility and severity, and its association with mental health and QoL in children with chronic skin disorders. A total of 1671 children aged 8-17 years (57.9% girls; mean age, 13.7 years) were recruited from 32 pediatric dermatology centers in the United States and Canada from November 2018 to November 2021. The most common conditions were acne, atopic dermatitis/eczematous disorders, alopecia, and psoriasis, but rare genetic disorders were also represented. The primary outcome was the extent of stigmatization in relation to disease visibility, assessed using the Patient-Reported Outcomes Measurement Instrumentation System Pediatric Stigma-Skin. Secondary outcomes were the extent of stigmatization in relation to disease severity, along with QoL, depression, anxiety, and poor peer relationships. TAKEAWAY: Approximately half (56.4%) of the children self-reported their skin condition as highly visible; 50.5% reported their disease severity as moderate, while 21.3% reported it as severe. Stigma was experienced by 73% of children and adolescents with chronic skin disease, with 43.8% reporting moderate stigma. Stigma scores correlated strongly with impaired QOL (Spearman ρ = 0.73) and child-reported scores for depression (ρ = 0.61) and moderately with anxiety (ρ = 0.54) and peer relationships (ρ = −0.49; all P < .001). Although stigma is increased for children with higher disease visibility and severity, the relatively weak correlation between child-assessed disease visibility and stigma (ρ = 0.22) showed that stigma is common in children even when diseases are not highly visible. IN PRACTICE: "Better treatment approaches for chronic skin diseases in children remain an unmet need. Increased awareness and instituting medical and psychological interventions to identify and reduce stigma and disease severity are important directions for improving QOL," the authors concluded. Note: This article originally appeared on Medscape

Keypoint: ADHD medications do not increase mania for patients with bipolar disorder when used alongside mood stabilizers. A systematic review published in Bipolar Disorders found that adjunctive attention-deficit/hyperactivity disorder (ADHD) medications are effective in improving comorbid ADHD symptoms – but not overall cognition – among patients with bipolar disorder. Both bipolar disorder and ADHD have overlapping psychopathology and potentially similar pathophysiology. The 2 disorders are also frequently comorbid and have both been associated with cognitive impairments due to abnormal dopamine and norepinephrine signaling. Because ADHD medications are effective in improving cognition and daily functioning among patients with ADHD, they are also sometimes used off-label for the treatment of ADHD symptoms and cognitive impairment among patients with bipolar disorder. To evaluate the effectiveness and safety of established and off-label use of ADHD medications for cognition and/or comorbid ADHD symptoms among patients with bipolar disorder, investigators from the International Society for Bipolar Disorders (ISBD) conducted a systematic review of the literature. The ISBD searched publication databases through June 2023 for relevant studies that examined ADHD pharmacotherapy among patients with bipolar disorder and reported on both changes in neurocognitive function or ADHD symptoms as an outcome and side effects experienced by patients. The investigators included a total of 17 studies comprising 2136 patients. Of the included studies, 12 examined stimulant ADHD medications and 5 evaluated nonstimulant medications. The 2 most commonly studied medications were armodafinil (k=4; n=1581) and methylphenidate (k=4; n=84). In the studies of methylphenidate, patients received between 5 and 40 milligrams per day administered in 2 daily doses in combination with mood-stabilizing medications (primarily lithium). Methylphenidate was found to be more effective than placebo among children and adolescents at reducing symptoms of ADHD in 2 studies. However, methylphenidate did not significantly improve mood symptoms in 1 of the included studies. Further, a study of children and adolescents with bipolar disorder did not report significant effects of methylphenidate on ADHD symptoms relative to placebo. Among adults, methylphenidate was not favored over placebo for the outcomes of cognition or mania. In a placebo-controlled trial that evaluated the effect of other stimulant medications on ADHD symptoms in pediatric bipolar disorder, the use of amphetamine salts (5 mg/d) adjunctive to divalproex sodium was associated with significant reductions in ADHD symptoms compared with placebo. For nonstimulant ADHD medications, clonidine (0.2-0.6 mg/d, dosed twice daily) with lithium or valproate sodium among adults was associated with significant reductions in the severity of manic symptoms and sleep disturbances, but no change was observed in cognition. The interventions were generally well-tolerated, especially when administered as an adjunctive with mood-stabilizing agents. However, review authors could not come to a consensus on nonpsychiatric side effects due to heterogeneity and uncertainty regarding how the studies monitored these side effects. The review authors concluded, “Given this good safety profile of the medications and paucity of research into their possible cognitive benefits, we encourage further research into the pro-cognitive potential of these medications in [bipolar disorder].” The major limitation of this review is that the investigators could not conduct a meta-analysis due to study heterogeneity and limited data. Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. Note: This article originally appeared on Psychiatry Advisor

Keypoint: The COVID-19 mRNA vaccines are effective for individuals with psychiatric disorders. Although psychiatric disorders increase COVID-19 hospitalization risk, mRNA COVID-19 vaccine effectiveness is not affected by psychiatric disorder status, according to study results published in Influenza and Other Respiratory Viruses. Previous research indicates that psychiatric disorders may be risk factors for severe manifestations of COVID-19 that result in hospitalizations and mortality. Additionally, psychiatric symptoms have been associated with a reduced immune response to influenza, measles, and hepatitis B vaccines. However, relatively little is known about whether psychiatric disorders affected COVID-19 vaccine effectiveness. To close this knowledge gap, researchers conducted a retrospective cohort analysis of 4 health systems across 4 states in the United States from December 2021 to August 2022. The researchers analyzed electronic health records to explore the association between psychiatric disorders and COVID-19 vaccination status, age group, and type of psychiatric disorder. The primary outcomes of interest were COVID-19 vaccine effectiveness and COVID-19-associated hospitalization among persons with and without psychiatric disorders. The researchers also evaluated whether the outcomes varied by number of mRNA vaccine doses. The study included 2,436,999 participants (median age=47 years), of whom 58.3% were women and 66.1% were White. At each patient’s start date with their health care system, 41.6% of participants were unvaccinated, 35.7% had received 2 vaccine doses and 22.7% had received 3 doses. Additionally, 22% of participants had a psychiatric disorder. The most common disorder was anxiety (13.6%), followed by mood disorders (12.9%), trauma- and stressor-related disorders (3.1%), attention-deficit/hyperactivity disorder (1.9%), and psychotic disorders (1.0%). The researchers found that patients with psychiatric disorders displayed a markedly higher incidence of COVID-19-associated hospitalization (hazard ratio [HR], 2.53; 95% CI, 2.36-2.70) at 394 per 100,000 person-years, relative to156 per 100,000 person-years for those without psychiatric conditions. This elevated risk remained robust even after controlling for demographics, vaccination status, and number of vaccination doses (adjusted hazard ratio [aHR], 1.27; 95% CI, 1.18-1.37). When stratified by psychiatric disorder type, the highest risk for COVID-19-associated hospitalization was observed for mood disorders (aHR, 1.25; 95% CI, 1.15-1.36), anxiety disorders (aHR, 1.33; 95% CI, 1.22-1.45), and psychotic disorders (aHR, 1.41; 95% CI, 1.14-1.74). However, the researchers did not observe a significant interaction between psychiatric disorder status and either age groups (P =.55) or COVID-19 vaccination status (P =.34). These findings indicate that the increased risk associated with psychiatric disorders was consistent regardless of age or vaccination status. Although hospitalization risk was higher among patients with psychiatric disorders, COVID-19 vaccination effectiveness did not significantly vary between groups. Among individuals with any psychiatric disorder, aHRs for the association between vaccination and hospitalization were 0.35 (95% CI, 0.25–0.49) with 2 vaccination doses and 0.08 (95% CI, 0.06–0.11) for 3 doses, relative to unvaccinated patients. These patterns of COVID-19 vaccine effectiveness were consistent across age, affirming that vaccination significantly lowers hospitalization risk irrespective of psychiatric status. In a press release, study co-author and vice president for data and analytics at Regenstrief Institute, Shaun Grannis, MD, MS, stated, “For patients with a diagnosis of depression, anxiety, or mood disorders who are wondering if the COVID vaccine would be valuable, this paper gives us evidence that the vaccine maintains its effectiveness even in the face of mental illness. So, I would encourage vaccination because it reduces the risk of hospitalization significantly.” Study limitations include the lack of information on the severity or trajectory of specific symptoms, the possibility of misclassification, and the lack of data on pharmacologic and behavioral treatments for psychiatric disorders. Disclosure: Multiple study authors reported affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. Note: This article originally appeared on Psychiatry Advisor