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Keypoint: This 2024 APA Annual Meeting poster covered a literature review on the relationship between stimulant use and failure to thrive in pediatric patients with ADHD. CONFERENCE REPORTER Addressing attention-deficit/hyperactivity disorder (ADHD) while ensuring the proper physical development of child and adolescent patients can be a challenge. A holistic, multidisciplinary approach to managing failure to thrive (FTT)—a condition in which children do not grow at a rate for their age—is critical. This includes a psychiatric consultation to address comorbidities. The poster, “Stimulant Use in Pediatric ADHD: Balancing Behavioral Management and Physical Development - A Case Study and Literature Review,” presented at the 2024 American Psychiatric Association Annual Meeting, reviewed the current literature on the relationship between stimulant use and FTT. To demonstrate findings, it presented a new case involving an adolescent patient with comorbid ADHD and conduct disorder. The investigators used methylphenidate as an example, a commonly prescribed ADHD medication for children aged 6 and older that is known for its appetite-suppressing effects. A young patient taking methylphenidate for their ADHD could experience appetite-suppression, thus leading to lower body mass index (BMI) and inadequate weight gain; inadequate weight gain could in turn lead to the patient experiencing FTT, also known as weight faltering. In cases of pediatric patients with both FTT and ADHD, clinicians must carefully balance the management of ADHD symptoms against the risk of appetite suppression associated with stimulants. Alternatively, not treating ADHD can increase the potential of depression and conduct disorders; in fact, 1 analysis suggested that depression was 20% less common during periods of time when patients received ADHD medication compared with periods when they did not. The study presents “Patient K,” a 14-year-old boy with ADHD, conduct disorder, and intellectual disability exhibited FTT. He was diagnosed with ADHD and conduct disorder early in childhood and has been prescribed methylphenidate since the age of 6. The use of stimulants initially improved his conduct, but slowed his growth trajectory with a significant BMI decrease. His clinicians identified methylphenidate as a potential cause and discontinued it, then putting him on guanfacine for ADHD and cyproheptadine to increase appetite. Unfortunately, the stimulant discontinuation resulted in behavioral and intellectual functioning issues; he displayed worsening aggression and intellectual regression. This led to reintroduction of methylphenidate at a reduced dose. While his behavior improved modestly, he experienced significant weight loss and did not recover the full extent of intellectual capacity. When consulted, psychiatry recommended to simplify his medication regimen for concerns of polypharmacy and to reduce adverse effects. The literature review used articles published in English from databases such as PubMed, PsycINFO, and Psychiatry Online. Cases not involving ADHD or stimulant use were excluded. This study illuminates the complex relationship between stimulants, behavioral management, and physical wellness, and contributes to a more complete understanding of ADHD treatment in pediatric populations. Additional research indicates long-term ADHD medication use is associated with increased risk of incident of cardiovascular disease regardless of age, indicating clinicians should not only carefully consider medication options for patients with this disorder, but also closely monitor those taking ADHD medications, especially in higher doses. Note: This article originally appeared on Psychiatric Times

Keypoint: Are individuals with bipolar disorder more likely to die from unnatural causes than the general population? CONFERENCE REPORTER A poster at the 2024 American Psychiatric Association (APA) Annual Meeting discussed the results of a recent meta-analysis that investigated the risk of premature mortality, particularly due to unnatural causes like suicide, among individuals with bipolar disorder compared with the general population. According to the poster’s researchers, there is an association between bipolar disorder and premature mortality. Individuals with bipolar disorder face heightened susceptibility to unnatural deaths, predominantly through suicide, alongside other unnatural causes such as homicide and accidents. The study discussed in the poster undertook a meta-analysis of current research findings concerning these unnatural causes, with a specific focus on suicide in bipolar disorder. Following PRISMA guidelines, the study researchers retrieved relevant data from multiple databases including PubMed, Embase, Web of Science, and PsycINFO. A total of 25 studies on suicide and 17 studies on unnatural causes were included in the analysis, which encompassed 180,210 individuals with bipolar disorder for suicide and 349,744 individuals with bipolar disorder for unnatural causes. The standardized mortality ratio (SMR) for suicide and unnatural causes was higher in individuals with bipolar disorder compared with the general population. Specifically, the relative risk (RR) for suicide was 11.69, with higher SMR observed in women (17.53) compared with men (14.02). Similarly, the SMR for unnatural causes was 7.29, with higher RR observed in females (9.33) compared with males (6.69). Meta-regression analysis showed no significant influence on results, and publication bias was not observed. According to the researchers, the study emphasizes the urgent need for suicide prevention efforts, particularly among individuals with bipolar disorder, as suicide remains a leading cause of preventable death in this population. These findings also underscore the importance of addressing suicide risk factors at both the individual and the population levels through clinical interventions and public health policies. “As supported by the data collected, in agreement with previous literature, bipolar disorder subjects presented elevated mortality from unnatural causes—suicide being the most concerning, as it is the leading cause of preventable death,” the researchers concluded. “Our findings lead to an understanding that an effort to prevent suicide is necessary mainly in high-risk bipolar disorder. Clinicians (individual level) and public health policies (populational level) should address risk factors for suicide.” The poster was presented by Beny Lafer, MD, PhD, of the University of Toronto Department of Psychiatry, and Taís Biazus, MD, of the University of São Paulo Medical School Department and Institute of Psychiatry. The suicide rate in the United States recently reached its highest peak since 1941.2 Are you interested in learning more about the latest research on suicide? See the Psychiatric Times® April cover stories on suicide in the context of various comorbidities and patient populations: A Year of Record-High Suicide Rates The suicide rate in the United States recently reached its highest peak since 1941. Here’s what you need to know. Managing Suicidal Thoughts, Behaviors, and Risk in Treatment-Resistant Depression Which therapeutic targets are likely to be relevant for reducing risk of suicide in TRD? Preventing Clinician Suicide Although the practice of medicine can be immensely rewarding, it also can be extraordinarily stressful. Here’s how we can help prevent clinician suicide. Note: This article originally appeared on Psychiatric Times®

Keypoint: This 2024 APA Annual Meeting poster documented the abuse potential of benzodiazepines and tapering challenges. ONFERENCE REPORTER Benzodiazepines, a controversial treatment widely prescribed for anxiety and insomnia, carry a considerable risk of abuse. The poster, “Mood over Matter: literature review on benzodiazepine tapering, current practices and updates on adjunct mood stabilizers,” presented at the 2024 American Psychiatric Association Annual Meeting, summarized a literature review of current benzodiazepine tapering practices, outpatient detoxification challenges, and potential barriers to discontinuation.1 The presenters also prioritized reviewing literature that highlighted mood stabilizer adjunct use. Here is some of the research the presenters featured: -A recent study reveals that between 2014 and 2016, an estimated 25.3 million US adults (10.4%) reported using benzodiazepines, and approximately 17.2% of these individuals admitted to misuse.2 -The National Institute on Drug Abuse documented that benzodiazepines were implicated in over 14% of opioid overdose deaths in 2021.3 -A report from the Centers for Disease Control and Prevention pinpointed benzodiazepines as a factor in nearly 7000 overdose deaths across 23 states from January 2019 to June 2020, constituting 17% of all drug overdose deaths. This timeframe saw a staggering 520% surge in deaths related to illicit benzodiazepines, while fatalities from prescribed benzodiazepines rose by 22%.4 Challenges to tapering patients with chronic benzodiazepine use include: -Difficulty tolerating intense withdrawal symptoms -Heightened anxiety -Mood shifts -Disrupted sleep -Tremors The presenters believe psychiatric and addiction-focused clinicians play an integral role in preventing benzodiazepine misuse, abuse, and addiction. In order to help patients taper benzodiazepines to discontinuation, clinicians must be up to date on practices; if clinicians mismanage tapering, sudden withdrawal can prove fatal. As to tapering strategies, the presenters suggested adjunct mood stabilizers such as carbamazepine and oxcarbazepine. Carbamazepine, used as an adjunct or prophylactically, can help reduce intense withdrawal symptoms and thus keep patients on track for discontinuation. However, carbamazepine has received criticism regarding its efficacy, and is well documented to have a series of concerning adverse effects such as skin reactions, agranulocytosis, leukopenia, and significant drug-drug interactions by nature of its metabolism. This makes some clinicians wonder: are the risks are worth the benefit? Oxcarbazepine has also been proposed as an alternative. Some small-scale clinical trials noted moderate efficacy for oxcarbazepine in helping patients with detoxification and it has fewer adverse effect concerns. The presenters suggested that other mood stabilizers, particularly those with anti-epileptic effects, require further research for their potential help with benzodiazepine addiction. “Through a more current literature review, we hope to increase the tools available to psychiatrists for more success in discontinuation and maintaining sobriety for patients,” wrote the presenters. However, others—like Psychiatric Times columnist Daniel Morehead, MD—suggest that while benzodiazepines certainly carries risks, those risks are exaggerated by government officials, critics, and the public at large.5 Steve Adelman, MD, suggests 8 universal precautions adapted from Gourlay et al for use by psychiatrists who must decide whether to initiate or continue pharmacotherapy with benzodiazepines. Note: This article originally appeared on Psychiatry Advisor

Ketamine clinic popularity has surged in recent years, with a growing number of psychedelic med spas appearing across the United States and globally. However, patients and providers alike have raised regulatory, legal, efficacy, and safety concerns about these clinics. Ketamine: From Club Drug to Breakthrough Therapy In the 1970s, ketamine was considered a single-use anesthetic confined to intravenous or intramuscular injection at a surgeon’s office. But it wasn’t long before ketamine emerged beyond the walls of the inpatient setting onto the club scene, where it became a highly popular recreational drug given its dissociative effects. By 1999, this gained the attention of the Drug Enforcement Administration (DEA), which then classified ketamine as a Schedule III controlled substance due to its high risk of dependence, lethal side effects, and potential for abuse. Despite its controversial history, interest in ketamine for therapeutic applications began to build around 2015 and in recent years there has been a rapid rise of ketamine clinics, enthusiastic to meet this newfound demand. These clinics offer off-label ketamine for a wide range of conditions, including neuropathic pain, anxiety, Lyme disease, and rheumatoid arthritis.2 As ketamine clinics popped up around the country, the Food and Drug Administration (FDA) approved a nasal spray containing esketamine (the S+ enantiomer) in 2019, called Spravato®, which is approved in conjunction with an oral antidepressant for 1) treatment-resistant depression and 2) patients with major depressive disorder (MDD) presenting with acute suicidal ideation or behavior. Although only meant for these specific indications, the approval of Spravato® helped drive ketamine’s perceived legitimacy for chronic disease management. Shortly after Spravato® was approved, the COVID-19 pandemic took over the world and led to a major shift in medical treatment modality as telehealth became both necessary and increasingly popular. As a result, a deregulated ketamine marketplace flourished online under the cover of telemedicine. This expanding market has raised serious red flags among healthcare providers and government agencies, now playing catch-up to protect public safety. To understand if today’s ketamine clinics are serving patients’ best interests — or simply taking advantage of a lucrative loophole — we spoke with Lisa M Harding, MD, Board Certified Psychiatrist and Assistant Clinical Professor at Yale School of Medicine, and Griffen Thorne, JD, Partner Attorney at Harris Sliwoski, to learn more. Do Ketamine Clinics Benefit Patients? On the surface, ketamine clinics seem to improve access to care for patients in rural areas or places with limited resources. However, Dr Harding is skeptical about the sudden proliferation of ketamine clinics, especially as they don’t take insurance. “Access to care has never meant giving substandard care. The folks operating in a space with no formal rules say they are improving access to seem less nefarious,” she explained. “There is no way that one kind of treatment required by the FDA to be delivered in a medical setting is equal to a similar treatment delivered outside of a medical setting just because there are no written rules. The safety challenges are still there.” While early ketamine clinics relied on intravenous infusion centers with medical supervision, today’s online clinics allow clients to fill generic prescriptions in the form of lozenges that they then take at home with the help of a designated “sitter” — who isn’t necessarily a medical professional. “Ketamine is now prescribed online, and in some cases even mailed to patients,” shared Thorne. But this wasn’t always the case. “A federal law, the Ryan Haight Act of 2008, prohibited physicians from prescribing controlled substances without at least 1 in-person evaluation beforehand. But this requirement was suspended during the COVID public health emergency declaration, so now things that weren’t available before are now available online. Some of these laws didn’t immediately change back after the COVID emergency ended,” he said. Nonetheless, some patients argue that at-home ketamine has been a life-changing treatment and advocate for the continued allowance of telemedicine ketamine treatment. “The DEA is trying to work through a middle ground where telehealth is still available for those who need it,” explained Thorne. However, many psychiatrists and regulators worry that ketamine treatment outside of a medical setting puts patients at risk. Dr Harding explained, Ketamine was only studied in the short term. No long-term efficacy study has been done on ketamine. Many papers look at retrospective data or comment on models implemented at academic institutions. For example, most patients in treatment with intravenous ketamine get treated once a month with an infusion and are evaluated with a face-to-face physician visit every 3-6 months once they are stable. However, she shared that esketamine does have a long-term safety study (the Sustain III trial), which enabled the approval of Spravato®. “Patients are treated once a week or once every two weeks, and the data published at the 4-year mark show no new safety signals. Patients in maintenance are assessed by their care team.” Dr Harding notes in her published work that esketamine is the only antidepressant of its kind to be researched and FDA-approved for depression symptoms in suicidal patients. It works within hours of administration, offering a significant advantage over other antidepressants that can take weeks. The FDA only approved Spravato® to be administered in a regulated environment. A Risk Evaluation and Mitigation Strategy (REMS) requires patients to stay in an approved facility for monitoring 2 hours after treatment and data is recorded after every treatment. These safeguards don’t apply to the off-label ketamine often provided at ketamine clinics. Is It Legal to Prescribe Ketamine? Ketamine can regularly be administered under the supervision of a licensed doctor in a medical setting, but ketamine prescriptions for at-home use aren’t legal in every state.8 Thorne advised, “Physicians who want to administer ketamine need a DEA registration like any other Schedule III controlled substance.” Because of the many state, federal, and healthcare regulations that exist, Thorne recommends having a robust compliance plan before operating a ketamine clinic. He said the rules change regularly, and what works in some states won’t pass in others. For example, certain states like New York and California have a rule called the Corporate Practice of Medicine (CPOM). This means that businesses like ketamine clinics generally must be owned by a licensed physician. However, CPOM laws vary greatly from state to state, so the requirements in one state may be completely inapplicable to its neighbor. Furthermore, states that don’t require CPOM may have different licensing requirements that need to be followed. “With ketamine, you deal with healthcare regulations, which are very complicated. And it’s all regulated under state law.” He discussed how this differs from cannabis, which is a Schedule 1 controlled substance. Any time a state legalizes cannabis for recreational use, it still cannot legally be prescribed because it is a Schedule I controlled substance. Doctors can recommend cannabis to patients who can purchase it themselves from a dispensary. But ketamine, which requires a prescription and is subject to greater penalties, is much more heavily regulated in its prescription and administration. Thorne also noted that just because someone is a doctor and has the legal authority to prescribe ketamine, it doesn’t necessarily mean they’re the best person for the job. “There are all kinds of licensed folks who try to get in on the action, which can lead to some concern, like if you’re dealing with ketamine therapy and you’re actually a podiatrist. Typically, anesthesiologists are involved, especially with infusions. Getting the right people is one of the main issues, especially if you want the drug to be given in a safe, effective, and appropriate way,” said Thorne. The Future of Ketamine and Other Drugs Thorne admits that some providers push the limits when it comes to prescribing off-label ketamine. He predicts that more regulation is likely as a result. He also suspects that certain psychedelic drugs are likely to get approved in the next few years, and the DEA will make more rules on how clinics can operate. “There’s a big interest in all the psychedelics, and there’s a strong chance of approval by 2026, if not sooner, for MDMA and maybe even psilocybin drugs,” Thorne explained. “Oregon has some state allowances for psilocybin, which are soon to come for Colorado. But there isn’t a retail market where you can buy and take it home. It’s all in an office or ‘service center,’ and someone licensed needs to watch you through the course of the drug. If a physician is to participate in that process, it’s not clear to say whether the state boards will approve it.” Thorne goes on to describe how cost can be a barrier. It would be a challenge to have insurance cover it. In some ways, these state-level programs are designed to fail because it’s a long time for a licensed facility to be there monitoring. It’s not a sustainable market because only a select group of people can afford it. If it’s going to be so expensive, people will need it to be insured at the federal level, which won’t happen with things like MDMA and psilocybin until the FDA approves them, at the very least. Even with ketamine, which has been used clinically for years, most physicians still only take cash. According to Dr Harding, the need for more mental health therapies is apparent, but she’s not convinced that ketamine or psychedelics are the answer. “To date, there is no cure for depression,” she shared. “Data tells us that if a patient has more than three bouts of depression, they will be in care for the majority of their life and will always be at risk. Treatment is always individualized, and there must always be informed consent. Patients must understand the risks, benefits, alternatives, and risks of no treatment at all.” Dr Harding agreed that patients need more options to care for their mental health, but only when supported by solid evidence. “I think there should be further trials to support mood disorders. We don’t have good treatments for [post-traumatic stress disorder] or bipolar depression. But we need clinical trials to support us,” she said. For now, Dr Harding encourages providers and patients to use caution when it comes to ketamine. “For providers, there is a lot of continuing education through the American Psychiatric Association to understand specific state laws… For patients, talk to your current treating providers. They are connected in communities and can connect you with care. Not every treatment is right for you. If an expert tells you that they don’t think it will help, they are probably right,” she advised. Note: This article originally appeared on Psychiatry Advisor

Keypoint: Brexpiprazole is safe and effective for reducing agitation associated with dementia due to Alzheimer Disease. Treatment with brexpiprazole was associated with significant reductions in agitation among patients with dementia due to Alzheimer Disease (AD), according to study results presented at the American Association of Geriatric Psychiatry (AAGP) 2024 Annual Meeting, held in Atlanta, Georgia, from March 15 to 18, 2024. For both patients and caregivers, the manifestation of agitation can be one of the most difficult symptoms to manage in dementia due to AD. Agitation often co-presents with psychosis symptoms and is typically an indication of accelerated disease progression. Consequently, there has been increased attention to potential pharmacological treatments for agitation and/or aggression in this patient population. To this aim, researchers are evaluating the efficacy and safety of brexpiprazole as a potential treatment option. The researchers conducted a post hoc analysis of data from 2 separate 12-week, phase 3, randomized placebo-controlled trials to evaluate the use of brexpiprazole in patients with agitation associated with dementia due to AD. The primary outcome of interest was the change in Cohen-Mansfield Agitation Inventory (CMAI) Total score from baseline to week 12, and the researchers also assessed baseline psychosis using the Neuropsychiatric Inventory (NPI) delusion item and/or hallucination item score. A total of 610 patients were evaluated, of which 363 patients received brexpiprazole (2 or 3 mg/day) and 247 received a placebo.1 The researchers reported that 142 patients had baseline psychosis while 465 were categorized into the patient subgroup without baseline psychosis. At week 12, the mean change in CMAI score was greater among the patient group receiving brexpiprazole relative to the placebo group.1 Among patients with baseline psychosis, the researchers found that the mean change in CMAI score with use of brexpiprazole was significantly higher than placebo (-25.1 vs -19.1; P =.043).2 Treatment with brexpiprazole was similarly efficacious among the patient subgroup without baseline psychosis (-20.5) relative to placebo (-16.3; P =.0021).2 Additionally, brexpiprazole demonstrated greater reduction across all NPI outcome scores at week 12, compared with placebo. Across each patient subgroup, the incidence of treatment-emergent adverse effects (TEAEs), serious TEAEs, and severe TEAEs were similar.2 The incidence of deaths was highest among patients with baseline psychosis taking brexpiprazole (1.3%) compared with placebo (0.0%) and relative to those without baseline psychosis (brexpiprazole:, 0.8%; placebo, 0.3%). All other adverse outcomes including sedation, incidence of falls, somnolence, TEAEs for cerebrovascular events, and TEAEs for cardiovascular events were less than 5% in both patient subgroups. Investigators also conducted a systematic review and network meta-analysis to determine the most efficacious and safe pharmacological treatment for agitation in patients with dementia.4 Data were extracted from a total of 28 RCTs, 19 of which analyzed patients with dementia due to AD. The investigators found that agitation/aggression was significantly lower among the groups taking brexpiprazole (mean difference [MD], -3.86; 95% CI, -6.03 to -1.12) and risperidone (mean difference [MD], -2.55; 95% CI, -4.70 to -0.57) relative to placebo. Brexpiprazole and risperidone were also more efficacious than memantine (MD, -7.65; 95% CI, -13.1 to -1.69 and MD, -6.37; 95% CI, -11.91 to -0.81) and haloperidol (MD, -5.6; 95% CI, -9.3 to -1.16 and MD, -4.28; 95% CI, -7.58 to -1.02) in improving agitation/aggression. These study findings indicate that brexpiprazole is efficacious in reducing agitation and baseline psychosis across AD-related dementia patient subgroups. The abstract authors concluded, “Brexpiprazole showed larger improvement than placebo, and higher response rates based on a meaningful within-patient change threshold, regardless of dementia severity, presence or absence of co-occurring neuropsychiatric symptoms, use of concomitant treatments for dementia or psychiatric conditions, and care setting.”1 Study limitations include small sample sizes for certain subgroups and a lack of research on the long-term effects of these medications. This article originally appeared on Psychiatry Advisor

The Human Rights Campaign has declared a national state of emergency for LGBTQ+ Americans. The transgender community in particular is facing an unprecedented amount of legislative violence, which threatens their families, education, health care, and public existence. When trans folks are forced to navigate both individual discrimination and systemic oppression, conversations about mental health must acknowledge their existence within an ecosystem that hasn’t prioritized their humanity – much less their wellness. But just as there are forces attempting to restrict the trans community, there are also those working tirelessly to uplift and enable trans individuals to thrive. Building on the community’s rich history of resilience, young trans change-makers are leading the way for a more inclusive future. Here are tips from Cyn Gomez and Rei Scott, former members of Mental Health America’s Young Leaders Council, for other young trans folks navigating these challenging times. Young Trans 1. Find Safe Ways To Explore And Celebrate Your Identity. Whether it’s because of their location, family, or other intersecting identities, some folks are more vulnerable to anti-trans harm than others. If you aren’t in an affirming environment, there are still ways to safely explore and express your gender identity. “You do not have to go telling everyone in your school that you're trans,” said Scott. “If you just want to try out new pronouns with a friend, that's a way that you can express yourself without putting yourself in danger.” When he was younger, Gomez had a friend help him purchase his first chest binder so that he wouldn’t be outed to his family. The friend had it delivered to their house in case the packaging wasn’t discrete. Scott recalled going to stores when he was younger to try on clothing that made him feel confident and affirmed – something he could do more freely within the privacy of a dressing room. “Quiet expressions of pride are just as meaningful,” said Scott. “When it comes to pride, being proud of yourself is more important than other people being proud of you. It's really important to learn to accept and embrace yourself because there are always going to be people who don't.” 2. Accept The Care Of The Trans Community – Or Offer It Yourself. “I think things like rest and self-care are usually defined as very solitary, but that’s not always true,” Scott said. “For me, some of the times that I’ve felt the most rested are among other trans and non-binary people. It’s important to find a space where you feel safe to completely be yourself, with those who understand your experiences on a personal level.” Growing up, Scott didn’t know any other trans people in his area, so he found community in online spaces. Social media and online support groups can allow people to anonymously and safely connect with others who share similar experiences. “When so many different avenues of your life might feel taxing for you as a person and in your identity, it’s important to have people who don’t ask you to be digestible and communities where you don’t have to work so hard just to exist,” Gomez said. Gomez also emphasized the importance of both receiving care and offering it. He encourages trans folks who aren’t facing day-to-day violence to stay tapped into ways they can do their part for others in the community who aren’t safe. That can include letter writing campaigns, subsidizing affirming care through mutual aid, sharing resources, or just lending an ear. “Even when everything is preying on us as a community to crumble, we're still moving with grace and strength,” said Gomez. “We're finding ways to take care of each other and ensure one another's wellness. Frankly, we’re beating all the odds right now.” 3. Tap Into The Historic Strength Of Trans Elders And Ancestors. “Find the queer and trans elders in your life or in your community. In these challenging moments for our community, it can be really healing to see that there is ancestry to all of this,” Gomez said. “This isn’t a struggle that we’ve fought alone, and this isn’t a struggle that we’re fighting for the first time. It’s a huge testament to our community’s strength and the way we’ve historically taken care of each other to make sure we were able to get to this point.” One of the practices Scott found most restorative was writing cards to LGBTQ+ seniors with other members of his undergraduate Pride club. Older folks in the community can provide a lot of insight into past movements for trans rights, as well as serve as a reminder for younger people struggling to envision a future for themselves. It’s this history of resilience that Gomez sees as evidence that the trans community is uniquely equipped to shake up the status quo and meet challenges head on. Gomez added that being trans and choosing life every day is an act of resistance. “We see how much of a threat we are to these systems that are trying to break us down. We’ve been able to create an ecosystem that completely defies everything that’s expected of us,” said Gomez. “One of the central components of our community is radical resistance to any kind of conformity. We’re fighting compounded and intersectional harms, and we’re disrupting so many systems and power complexes.” “I feel like we often blame ourselves for our identity and place responsibility on ourselves for our oppression, but that’s not the truth,” Scott said. “There is nothing wrong with you. Your existence really means something. Being trans means something – and it’s something to be proud of. Even if you can’t feel that right now, I’m going to hold onto hope that you can in the future.” 4. Practice Radical And Unapologetic Rest. Both Gomez and Scott emphasized the importance of allowing time for true rest. “I think feeling disconnected from your body – especially when it can cause dysphoria – is one of the things that's very innate to transness, and that can make it really hard to know when you need to take care of yourself,” Gomez said. “When you’re existing in a fight-or-flight response all the time, you’re constantly tense and vigilant. We have to learn to really decompress and release that.” Gomez tries to incorporate healing practices into his organizing work, including somatic care and herbalism. He finds it important to do both individually and collectively, and he encourages folks to share their knowledge and restorative practices with other members of the community. “It is an act of resistance to rest,” says Gomez. Rest also includes knowing when to step back from conversations or conflicts that end up harming you. Scott is familiar with the labor of correcting people who refer to him with incorrect pronouns, and he acknowledges that it’s a battle that he isn’t always capable of fighting. “If you don’t feel comfortable talking about something or asserting something publicly, it’s totally okay not to,” said Scott. “That doesn’t make you any less trans or any less non-binary. You are still you, and you're still valid – you’re just protecting yourself.” 5. Center Trans Joy, Hope, And Creativity. Scott and Gomez both recognize that being trans is often traumatizing. But they also believe that trans identity shouldn’t be defined solely by the way individuals and systems treat (or mistreat) trans people. It’s possible to acknowledge oppression and make space for joyful trans experiences. “I think one of the most radical things our community can do is move away from organizing our community around fear,” Gomez said. “One of the strongest components of the trans community is our resilience and perseverance – and comrades in these deeply harmful spaces often embody that most directly.” Scott added, “There's a lot of power in artistic expression. I’ve attended events where I read my own poetry, including a poem I wrote about my chosen name. That was something so important to me, putting all these feelings into something more tangible and getting to express the positive parts about my identity.” Unable to access top surgery, Scott has been making an effort to focus on the parts of himself and his body that make him feel affirmed and empowered – rather than those that don’t. He connects with his identity through both his gender presentation and creative expression. “Trans joy is fighting and thriving in our existence outside of any expectation, with sheer people power and investment in one another,” said Gomez. “The systems and people who hope to see us fall thrive on our silence. They want us to be siloed, individualized, and compartmentalized. So when we coalesce and genuinely show up for one another, that is how we survive this.” This Pride Month, explore how to affirm your own gender/sexuality, be an active LGBTQ+ ally, and build supportive and affirming communities. Learn more here. Keep Up With Our Featured Youth Leaders: Rei Scott at @sealikesword Cyn Gomez at @thecyngomez Source: MHA National

Concurrent treatments targeting eating disorders and PTSD are needed to help these patients with complex conditions. Research shows an undeniable connection between posttraumatic stress disorder (PTSD) and eating disorders (EDs). Individuals with significant traumatic histories and/or PTSD have more severe ED symptoms, more suicidality, and more anxiety and depressive symptoms. Studying the intersection between these 2 mental health illnesses helps us understand how to treat them together moving forward, specifically in higher levels of care, including residential ED treatment programs. Groundbreaking research published in the Journal of Eating Disorders shows the effectiveness of integrating trauma treatment with evidenced-based ED treatment in residential programs. The conventional thinking in psychiatry had been that it was best to refrain from trauma work while in intensive treatment settings, deferring this to later outpatient treatment. These research results demonstrate that multimodal, integrated treatment approaches based on principles of cognitive processing therapy (CPT) that address trauma and PTSD can be successfully delivered in residential treatment to patients with PTSD and associated comorbidity. PTSD in Higher Levels of ED Treatment Research from the past few years indicates that PTSD is common in patients receiving higher levels of care. In 2020, we reported that nearly half (49%) of adults admitted to residential ED treatment met the criteria for PTSD,2 whereas results from an additional study from 2021 found that of 613 adults in residential treatment, 53% were reported to likely have PTSD based on PCL-5 >33.3 Furthermore, 35% of women in ED residential treatment also had PTSD, according to results from a 2021 study (Figure 1). Individuals with EDs and comorbid PTSD experience more severe anxiety, depression, ED symptoms, and poorer quality of life compared with those without PTSD. Adults with EDs and PTSD had significantly higher scores than patients without PTSD on all measures, including total number of traumas on the Life Events Checklist (P < .001), global and all subscale scores on the Eating Disorder Examination Questionnaire (P < .001), depression scores on the Patient Health Questionnaire (P < .001), and scores on the Spielberger State-Trait Anxiety Inventory (state P < .001; trait P < .001). Additionally, research shows that PTSD is common among adolescents who are admitted to ED residential programs. Adolescents with EDs and PTSD experienced more severe ED symptoms and poorer quality of life compared with those without PTSD in ED treatment. Our research reported that of the 647 adolescents with EDs admitted to residential treatment, 38% met criteria for PTSD and 75% endorsed at least 1 type of childhood trauma. Those who experienced ED onset from the age of 5 to 10 years had higher rates of PTSD (76%) compared with those who experienced ED onset from the age of 11 to 17 years (45%) and those who experienced ED onset as adults (31%; P < .001). Childhood onset of an ED is associated with more traumatic experiences and current PTSD diagnosis, increased severity of ED and comorbid psychopathology, higher body mass index, and more prior inpatient and residential admissions for ED treatment. Sexual and gender minority individuals in ED treatment have significantly higher rates of PTSD compared with those who do not identify as LGBTQ+. Individuals with EDs and PTSD who identify as LGBTQ+ experience more severe ED symptoms and poorer quality of life. Of the 24% of participants in our study who identified as LGBTQ+, 63% met criteria for PTSD compared with 45% of cisgender heterosexual individuals. Outcomes With Concurrent Treatment Using an integrated clinical approach based on principles of CPT and other evidence-based treatments, we studied outcomes at discharge and 6 months following discharge in 609 patients (96% female; mean age [+/- SD], 26.0 years [+/- 8.8 years]; 22% LGBTQ+) with and without PTSD. All patients improved significantly and retained improvements at follow-up compared with admission. However, all measured symptoms, including those of EDs, major depression, state and trait anxiety, and quality of life, were higher in patients with PTSD at every time point (admission, discharge, and follow-up). Going beyond trauma-informed care by providing evidence-based trauma treatment results in better outcomes. We integrated CPT, 1 of 3 gold-standard PTSD treatment options, into comprehensive ED treatment based on cognitive behavioral therapy and dialectical behavior therapy. Results from the study showed that 81% of patients with PTSD at admission had significant reductions in trauma symptom scores from admission to discharge and 73% of patients with PTSD at admission had significant reductions in scores from admission to follow-up 6 months later. Not only did patients achieve sustained improvements in ED symptoms, but they also gained significant, long-term relief from trauma symptoms after completing programming using an integrated, multimodal clinical approach. Postdischarge outcomes data show that not only treating patients’ mental health illnesses but also providing them with tools and coping skills to self-manage symptoms and maintain recovery can help patients get well and stay well longer. Concluding Thoughts There is growing consensus in the ED field that integrated, concurrent treatments targeting EDs and PTSD are needed to help these patients with complex conditions.2,4,7-10 The findings of this study conclude that concurrent, parallel, and interwoven approaches to treatment, one for the ED and one for PTSD, can be delivered during the same treatment course by the same providers and therapists. Integrated therapy techniques for PTSD and related disorders can be delivered successfully in residential treatment and are associated with lasting improvements 6 months after discharge (Figure 2). The hope for this research and these findings is that they may help others in the ED field develop more effective and integrated treatment approaches for patients with PTSD admitted to higher levels of care for ED treatment. Dr Perlman is chief medical officer at Monte Nido & Affiliates. She is double–board certified in psychiatry and addiction medicine and has trained in psychoanalytic psychotherapy. She is on the board of directors of the Eating Disorders Coalition, has served as vice president of the board from 2018 through 2022, and advocates in the US Congress regularly for increasing eating disorder education and access to treatment. Additionally, she oversees Monte Nido & Affiliates’ institutional review board–approved research study on clinical outcomes as coprincipal investigator and has coauthored several papers in peer-reviewed research journals on PTSD and EDs. Related Topic: Boundary Problems Associated with PTSD and Substance Abuse References 1. Brewerton TD, Gavidia I, Suro G, Perlman MM. Eating disorder patients with and without PTSD treated in residential care: discharge and 6-month follow-up results. J Eat Disord. 2023;11(1):48. 2. Brewerton TD, Perlman MM, Gavidia I, et al. The association of traumatic events and posttraumatic stress disorder with greater eating disorder and comorbid symptom severity in residential eating disorder treatment centers. Int J Eat Disord. 2020;53(12):2061-2066. 3. Scharff A, Ortiz SN, Forrest LN, Smith AR. Comparing the clinical presentation of eating disorder patients with and without trauma history and/or comorbid PTSD. Eat Disord. 2021;29(1):88-102. 4. Rienecke RD, Blalock DV, Duffy A, et al. Posttraumatic stress disorder symptoms and trauma-informed care in higher levels of care for eating disorders. Int J Eat Disord. 2021;54(4):627-632. 5. Brewerton TD, Gavidia I, Suro G, Perlman MM. Eating disorder onset during childhood is associated with higher trauma dose, provisional PTSD, and severity of illness in residential treatment. Eur Eat Disord Rev. 2022;30(3):267-277. 6. Brewerton TD, Suro G, Gavidia I, Perlman MM. Sexual and gender minority individuals report higher rates of lifetime traumas and current PTSD than cisgender heterosexual individuals admitted to residential eating disorder treatment. Eat Weight Disord. 2022;27(2):813-820. 7. Claudat K, Reilly EE, Convertino AD, et al. Integrating evidence-based PTSD treatment into intensive eating disorders treatment: a preliminary investigation. Eat Weight Disord. 2022;27(8):3599-3607. 8. Mitchell KS, Singh S, Hardin S, Thompson-Brenner H. The impact of comorbid posttraumatic stress disorder on eating disorder treatment outcomes: investigating the unified treatment model. Int J Eat Disord. 2021;54(7):1260-1269. 9. Trottier K, Monson CM. Integrating cognitive processing therapy for posttraumatic stress disorder with cognitive behavioral therapy for eating disorders in PROJECT RECOVER. Eat Disord. 2021;29(3):307-325. 10. Scharff A, Ortiz SN, Forrest LN, et al. Post-traumatic stress disorder as a moderator of transdiagnostic, residential eating disorder treatment outcome trajectory. J Clin Psychol. 2021;77(4):986-1003.

The concept that cognitive health can be preserved or improved is often expressed as "use it or lose it." Numerous modifiable risk factors are associated with "losing" cognitive abilities with age and a cognitively active lifestyle may have a protective effect. But what is a "cognitively active lifestyle" — do crosswords and Sudoku count? One popular approach is "brain trfaining." While not a scientific term with an established definition, it "typically refers to tasks or drills that are designed to strengthen specific aspects of one's cognitive function," Yuko Hara, PhD, director of Aging and Alzheimer's Prevention at the Alzheimer's Drug Discovery Foundation, told Medscape Medical News. Manuel Montero-Odasso, MD, PhD, director of the Gait and Brain Lab, Parkwood Institute, London, Ontario, Canada, elaborated. "Cognitive training involves performing a definitive task or set of tasks where you increase attentional demands to improve focus and concentration and memory," he told Medscape Medical News. "You try to execute the new things that you've learned and to remember them." In a commentary on Medscape Medical News, neuroscientist Michael Merzenich, PhD, professor emeritus at University of California San Francisco, said that growing a person's cognitive reserve and actively managing brain health can play an important role in preventing or delaying Alzheimer's disease. Important components of this include brain training and physical exercise. Brain Training: Mechanism of Action Montero-Odasso, who is also team leader at the Canadian Consortium on Neurodegeneration in Aging and team co-leader at the Ontario Neurodegenerative Research Initiative, explained that cognitive training creates new synapses in the brain, thus stimulating neuroplasticity. "When we try to activate networks mainly in the frontal lobe, the prefrontal cortex, a key mechanism underlying this process is enhancement of the synaptic plasticity at excitatory synapses, which connect neurons into networks; in other words, we generate new synapses, and that's how we enhance brain health and cognitive abilities." The more neural connections, the greater the processing speed of the brain, he continued. "Cognitive training creates an anatomical change in the brain." Executive functions, which include attention, inhibition, planning, and multitasking, are regulated predominantly by the prefrontal cortex. Damage in this region of the brain is also implicated in dementia. Alterations in the connectivity of this area are associated with cognitive impairment, independent of other structural pathological aberrations (eg, gray matter atrophy). These patterns may precede structural pathological changes associated with cognitive impairment and dementia. Neuroplasticity changes have been corroborated through neuroimaging, which has demonstrated that after cognitive training, there is more activation in the prefrontal cortex that correlates with new synapses, Montero-Odasso said. Henry Mahncke, PhD, CEO of the brain training company Posit Science/BrainHQ, explained that early research was conducted on rodents and monkeys, with Merzenich as one of the leading pioneers in developing the concept of brain plasticity. Merzenich co-founded Posit Science and is currently its chief scientific officer. Mahncke recounted that as a graduate student, he had worked with Merzenich researching brain plasticity. When Merzenich founded Posit Science, he asked Mahncke to join the company to help develop approaches to enhance brain plasticity — building the brain-training exercises and running the clinical trials. "It's now well understood that the brain can rewire itself at any age and in almost any condition," Mahncke said. "In kids and in younger and older adults, whether with healthy or unhealthy brains, the fundamental way the brain works is by continually rewiring and rebuilding itself, based on what we ask it to do." If we understand the principles of brain plasticity, "we can build an adaptive brain and give it exercises to rewire in a healthy direction, improving cognitive abilities like memory, speed, and attention," Mahncke said. Unsubstantiated Claims and Controversy Brain training is not without controversy, Hara pointed out. "Some manufacturers of brain games have been criticized and even fined for making unsubstantiated claims," she said. A 2016 review found that brain-training interventions do improve performance on specific trained tasks, but there is less evidence that they improve performance on closely related tasks and little evidence that training improves everyday cognitive performance. A 2018 review reached similar conclusions, calling evidence regarding prevention or delay of cognitive decline or dementia through brain games "insufficient," although cognitive training could "improve cognition in the domain trained." "The general consensus is that for most brain-training programs, people may get better at specific tasks through practice, but these improvements don't necessarily translate into improvement in other tasks that require other cognitive domains or prevention of dementia or age-related cognitive decline," Hara said. Hara noted that most brain-training programs "have not been rigorously tested in clinical trials" — although some, such as those featured in the ACTIVE trial, did show evidence of effectiveness. Mahncke agreed. "Asking whether brain training works is like asking whether small molecules improve health," he said noting that some brain-training programs are nonsense and not evidence-based. He believes that his company's product, BrainHQ, and some others are "backed by robust evidence in their ability to stave off, slow, or even reverse cognitive changes." BrainHQ is a web-based brain game suite that can be used independently as an app or in group settings (classes and Webinars) and is covered by some Medicare Advantage insurance plans. It encompasses "dozens of individual brain-training exercises, linked by a common thread. Each one is intensively designed to make the brain faster and more accurate," said Mahncke. He explained that human brains "get noisy as people get older, like a radio which is wearing out, so there's static in the background. This makes the music hard to hear, and in the case of the human brain, it makes it difficult to pay attention." The exercises are "designed to tamp down the 'noise,' speed up the brain, and make information processing more accurate." Mahncke called this a "bottom-up" approach, in contrast to many previous cognitive-training approaches that come from the brain injury rehabilitation field. They teach "top-down" skills and strategies designed to compensate for deficits in specific domains, such as reading, concentration, or fine motor skills. By contrast, the approach of BrainHQ is "to improve the overall processing system of the brain with speed, attention, working memory, and executive function, which will in turn impact all skills and activities." Supporting Evidence Mahncke cited several supporting studies. For example, the IMPACT study randomized 487 adults (aged ≥ 65 years) to receive either a brain plasticity–based computerized cognitive training program (BrainHQ) or a novelty- and intensity-matched general cognitive stimulation treatment program (intervention and control group, respectively) for an 8-week period. Those who underwent brain training showed significantly greater improvement in the repeatable Battery for the Assessment of Neuropsychological Status (RBANS Auditory Memory/Attention) than those in the control group (3.9 vs 1.8, respectively; P =.02). The intervention group also showed significant improvements on multiple secondary measures of attention and memory. The magnitude of the effect sizes suggests that the results are clinically significant, according to the authors. The ACTIVE study tested the effects of different cognitive training programs on cognitive function and time to dementia. The researchers randomized 2802 healthy older adults (mean age, 74 years) to a control group with no cognitive training or one of three brain-training groups comprising: In-person training on verbal memory skills In-person training on reasoning and problem-solving Computer-based speed-of-processing training on visual attention Participants in the training groups completed 10 sessions, each lasting 60-75 minutes, over a 5- to 6-week period. A random subsample of each training group was selected to receive "booster" sessions, with four-session booster training delivered at 11 and 35 months. All study participants completed follow-up tests of cognition and function after 1, 2, 3, 5, and 10 years. At the end of 10 years, those assigned to the speed-of-processing training, now part of BrainHQ, had a 29% lower risk for dementia than those in the control group who received no training. No reduction was found in the memory or reasoning training groups. Participants who completed the "booster" sessions had an even greater reduction: Each additional booster session was associated with a 10% lower risk for dementia. Montero-Odasso was involved in the SYNERGIC study that randomized 175 participants with mild cognitive impairment (MCI; average age, 73 years) to one of five study arms: Multidomain intervention with exercise, cognitive training, and vitamin D Exercise, cognitive training, and placebo Exercise, sham cognitive training, and vitamin D Exercise, sham cognitive training, and placebo Control group with balance-toning exercise, sham cognitive training, and placebo "Sham" cognitive training consisted of alternating between two tasks (touristic search and video watching) performed on a tablet, with the same time exposure as the intervention training. The researchers found that after 6 months of interventions, all active arms with aerobic-resistance exercise showed improvement in the ADAS-Cog-13, an established outcome to evaluate dementia treatments, when compared with the control group — regardless of the addition of cognitive training or vitamin D. Compared with exercise alone (arms 3 and 4), those who did exercise plus cognitive training (arms 1 and 2) showed greater improvements in their ADAS-Cog-13l score, with a mean difference of −1.45 points (P = .02). The greatest improvement was seen in those who underwent the multidomain intervention in arm 1. The authors noted that the mean 2.64-point improvement seen in the ADAS-Cog-13 for the multidomain intervention is actually larger than changes seen in previous pharmaceutical trials among individuals with MCI or mild dementia and "approaches" the three points considered clinically meaningful. "We found that older adults with MCI who received aerobic-resistance exercise with sequential computerized cognitive training significantly improved cognition," Montero-Odasso said. "The cognitive training we used was called Neuropeak, a multidomain lifestyle training delivered through a web-based platform developed by our co-leader Louis Bherer at Université de Montréal." He explained that the purpose "is to challenge your brain to the point where you need to make an effort to remember things, pay attention, and later to execute tasks. The evidence from clinical trials, including ours, shows this type of brain challenge is effective in slowing and even reversing cognitive decline." Puzzles, Board Games, and New Challenges Formal brain-training programs aren't the only way to improve brain plasticity, Hara said. Observational studies suggested an association between improved cognitive performance and/or lower dementia risk and engaging in number and word puzzles, such as crosswords, cards, or board games. Some studies suggested that older adults who use technology might also protect their cognitive reserve. Hara cited a US longitudinal study of more than 1800 older adults suggesting that regular internet users had roughly half the risk for dementia compared to nonregular internet users. Estimates of daily internet use suggested a U-shaped relationship with dementia with 0.1-2.0 hours daily (excluding time spent watching television or movies online) associated with the lowest risk. Similar associations between internet use and a lower risk for cognitive decline have been reported in the United Kingdom and Europe. "Engaging in mentally stimulating activities can increase 'cognitive reserve' — meaning, capacity of the brain to resist the effects of age-related changes or disease-related pathology, such that one can maintain cognitive function for longer," Hara said. "Cognitively stimulating activities, regardless of the type, may help delay the onset of cognitive decline." She listed several examples of activities that are stimulating to the brain, including learning a new game or puzzle, a new language, a new dance, and learning how to play a musical instrument. Montero-Odasso emphasized that the "newness" is key to increasing and preserving cognitive reserve. "Just surfing the internet, playing word or board games or doing crossword puzzles won't be enough if you've been doing these things all your life," he said. "It won't hurt, of course, but it won't necessarily increase your cognitive abilities." "For example, a person who regularly engages in public speaking may not improve cognition by taking a public-speaking course, but someone who has never spoken before an audience might show cognitive improvements as a result of learning a new skill," he said. "Or someone who knows several languages already might gain from learning a brand-new language." He cited research supporting the benefits of dancing, which he called "an ideal activity because it's physical, so it provides the exercise that's been associated with improved cognition. But it also requires learning new steps and moves, which builds the synapses in the brain. And the socialization of dance classes adds another component that can improve cognition." Mahncke hopes that beyond engaging in day-to-day new activities, seniors will participate in computerized brain training. "There's no reason that evidence-based training can't be offered in senior and community centers, as yoga and swimming are," he said. "It doesn't have to be simply something people do on their own virtually. "Zoom classes and Medicare reimbursements are "good steps in the right direction, but it's time to expand this potentially life-transformative intervention so that it reaches the ever-expanding population of seniors in the United States and beyond." Hara reported having no disclosures. Montero-Odasso reported having no commercial or financial interest related to this topic. He serves as the president of the Canadian Geriatrics Société and is team leader in the Canadian Consortium of Neurodegeneration in Aging. Note: This article originally appeared on Medscape

Keypoint: Frequent users had increased urine lead and uranium levels vs occasional users. HealthDay News — Teens who vape frequently have higher exposure to toxic metals, according to a study published online April 29 in Tobacco Control. Andrew Kochvar, from the University of Nebraska Medical Center in Omaha, and colleagues used data from wave 5 of the Population Assessment of Tobacco and Health Study Youth Panel to investigate factors associated with biomarkers of metal exposure among a nationally representative sample of U.S. adolescents (aged 13 to 17 years) who reported vaping. The analysis included 200 exclusive electronic cigarette users, 65 occasional users, 45 intermittent users, and 81 frequent users. The researchers found that both intermittent (0.21 ng/mg creatinine) and frequent users (0.20 ng/mg creatinine) had higher urine lead levels than occasional users (0.16 ng/mg creatinine). Higher urine uranium levels were also seen among frequent users versus occasional users (0.009 versus 0.005 ng/mg creatinine). Sweet flavor users (15.3 percent) had higher uranium levels versus menthol/mint users (33.0 percent; 0.009 versus 0.005 ng/mg creatinine). “By leveraging a national survey and biospecimen analysis, our study shows a correlation between vaping frequency and heightened metal exposure,” the authors write. “The findings of this study underscore the importance of implementing vaping regulations and targeted prevention strategies for adolescents.” Note: This article originally appeared on Psychiatry Advisor

Keypoint: First-degree relatives of individuals with TRD are 7.47 times more likely to develop TRD than individuals without a family history. Patients with a family history of treatment resistant depression (TRD) are at increased risk for antidepressant resistance and suicide mortality, relative to those without family history. These findings indicate that TRD treatment options beyond antidepressant monotherapy may be necessary for this patient population, according to results published in JAMA Psychiatry. In Major Depressive Disorder (MDD), combining or altering depression treatments earlier may be beneficial, given the clinical significance of a family history of treatment-resistant depression (TRD) for antidepressant resistance and increased suicide mortality, according to study results published Previous studies suggest that major depressive disorder (MDD) and TRD have a genetic component and may be transmitted across families. Although there is evidence that patients with TRD face increased mortality risks, relatively little is known about whether first-degree relatives are also at increased risk of mortality. The current study sought to explore the susceptibility to TRD within families and its association with treatment and mortality outcomes. Investigators conducted a cohort study using data from the Taiwan national health insurance database between January 2003 and December 2017. The investigators identified individuals with MDD (using International Classification of Diseases [ICD] codes) and defined TRD as failure to respond to 3 different antidepressants, validated via prescription records. Once the TRD cohort was determined, the investigators identified first-degree relatives (n=34,467). Additionally, the investigators created a 1:4 comparison group (n=137,868) of first-degree relatives of individuals without TRD, matched by age, sex, and kinship. Overall, 533,302 individuals were diagnosed with MDD and 21,046 had TRD. A total of 172,335 first-degree relatives (48.75% women) were included for analysis, of whom 34,467 were in the TRD relatives cohort and 137,868 were in the control cohort. On average, individuals were 22.9 (SD, 18.1) years of age at the beginning of follow-up. Relative to the control group, first-degree relatives of individuals with TRD had lower monthly incomes (P <.001), more physical comorbidities (P <.001), and a greater proportion lived outside of urban areas (P =.004). In a model adjusting for sex, birth year, comorbidities, income, urbanization, and more stringent TRD inclusion criteria, the investigators found that first-degree relatives of individuals with TRD had an increased risk of all-cause mortality (adjusted risk ratio[aRR], 1.21) and suicide mortality (aRR, 2.72). Results of the model also indicated a significantly elevated risk for developing TRD (aRR, 7.47), MDD (aRR, 3.57), bipolar disorder (aRR, 3.36), obsessive-compulsive disorder (aRR, 2.85), anxiety (aRR, 2.57), autism spectrum disorder (aRR, 2.35), attention-deficit/hyperactivity disorder (aRR, 2.22), and schizophrenia (aRR, 2.15). These mortality and psychiatric disorder risks remained robust even when excluding first-degree relatives who were themselves diagnosed with TRD. “Family history of TRD is a clinical risk factor due to its association with increased suicide mortality and resistance to antidepressant treatment; therefore, more intensive depression treatments, such as add-on pharmacotherapy or nonpharmacotherapy might be considered earlier,” the investigators concluded. A major study limitation is the strict definition of treatment-resistant depression, which may limit the generalizability of the study findings. Note: This article originally appeared on Psychiatry Advisor

Keypoint: Second-generation long-acting injectable antipsychotics reduce the risk for hospitalization among patients with first-episode psychosis and co-occurring cannabis use disorder. Clozapine, oral aripiprazole, and long-acting injectable (LAI) formulations of risperidone, aripiprazole, and paliperidone decrease the risk for hospitalization due to psychotic relapse among patients with first-episode psychosis (FEP) and comorbid cannabis use disorder (CUD). These findings from a nationwide cohort study were published in Schizophrenia Bulletin. Although cannabis use following a FEP event is associated with elevated psychotic symptom severity and more relapses, up to 50% of individuals with FEP have comorbid CUD. Yet, no nationwide studies have evaluated real-world outcomes of antipsychotic treatments among individuals with FEP and CUD. To address this knowledge gap, investigators used data from Swedish national registers to evaluate the efficacy of antipsychotics in reducing the risk for hospitalization among patients with FEP and co-occurring CUD. The primary exposure was dispensations of antipsychotic medications for FEP between 2005 and 2021 to individuals (N=1820) aged 16 to 64 years with co-occurring CUD diagnosed between 2006 and 2021. The primary study outcomes were hospitalization due to psychotic disorder, any psychiatric disorder, and/or any substance use disorder – confirmed via International Classification of Diseases, Tenth Revision (ICD-10), codes. Of the 1820 individuals included for analysis, 84.73% were boys and men, 43.57% achieved a medium level of education, and 55.55% earned income from work. On average, individuals were 26.8 (SD, 8.3) years of age. At the time of FEP, 33.9% of individuals had a diagnosis of harmful cannabis use, 32.4% had cannabis-induced psychosis, 20.6% had cannabis dependence, and 13.1% had other cannabis-related diagnoses. Most individuals were hospitalized for psychotic relapse (61%), any psychiatric diagnosis (76%), and any SUD (63%) during a mean follow-up of 6.13 years. The investigators found that the risk for hospitalization due to psychotic relapse was significantly lower among individuals who used LAI risperidone (hazard ratio [HR], 0.40), LAI aripiprazole (HR, 0.42), clozapine (HR, 0.43), LAI paliperidone (HR, 0.46), polytherapy (HR, 0.60), aripiprazole (HR, 0.61), and olanzapine (HR, 0.80). The risk for hospitalization was not decreased with LAI olanzapine, quetiapine, or risperidone. Overall, the use of any antipsychotic was associated with a 33% reduction of psychotic relapse risk (HR, 0.67), relative to non-use. When evaluating the risk for hospitalization for any psychiatric disorder, HRs were significantly lower among individuals who used LAI paliperidone (HR, 0.43), clozapine (HR, 0.44), LAI aripiprazole (HR, 0.45), LAI risperidone (HR, 0.53), polytherapy (HR, 0.69), aripiprazole (HR, 0.73), and olanzapine (HR, 0.83). Similarly, LAI olanzapine, quetiapine, and risperidone were not associated with significantly lower risk. For hospitalization due to any SUD, clozapine (HR, 0.14), LAI risperidone (HR, 0.33), LAI paliperidone (HR, 0.37), LAI aripiprazole (HR, 0.58), polytherapy (HR, 0.67), and olanzapine (HR, 0.82) were associated with decreased risk. The investigators concluded, “[T]hese findings encourage the early use of [second-generation antipsychotic] LAIs as an important secondary prevention strategy to reduce rates of hospitalization in FEP patients with comorbid CUD.” This study was limited by not having access to data about cannabis use trajectories, however, 63.6% of the study population were re-diagnosed with CUD during follow-up. Note: This article originally appeared on Psychiatry Advisor

Keypoint: Established focal neuromodulation therapies are generally considered safe from a cognitive standpoint. Focal neuromodulation therapies for psychiatric and neurological conditions are not generally associated with adverse cognitive effects, according to a review published in Nature Reviews Psychology. In fact, focal direct-to-brain neuromodulation has the potential to improve aspects of cognition by treating the underlying disorder. Health care providers and researchers are increasingly using focal neuromodulation therapies – such as transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and ablative techniques – to disrupt aberrant brain networks that contribute to clinical symptoms in neurological and psychiatric disorders. However, there is still concern that these approaches may also negatively affect normative cognitive processes. To address these concerns, investigators from Sunnybrook Research Institute in Canada conducted a systematic review to assess the effects of repetitive TMS, DBS, and ablative techniques on cognition among patients with major depressive disorder (MDD), obsessive-compulsive disorder (OCD), schizophrenia, Parkinson disease (PD), essential tremor, and Alzheimer disease (AD). Most studies employing repetitive TMS target the dorsolateral prefrontal cortex with the motivation of improving executive function. This treatment approach has been granted regulatory approval for use by the United States Food and Drug Administration (FDA) for treatment-resistant MDD. The body of research about repetitive TMS indicated that this approach likely did not impair cognition among patients with MDD, treatment-resistant OCD, schizophrenia, PD, or AD. Some studies reported improvements in cognition, however, the studies had conflicting findings and differing lengths of follow-up. Deep brain stimulation is an invasive modality that involves implanting electrodes unilaterally or bilaterally into target regions or fiber tracts. The implanted electrodes are connected to a power stimulator implanted in the chest. The FDA approved this technique for the treatment of PD and essential tremor and has regulatory approval by the US FDA for the treatment of OCD. In general, no evidence indicated that DBS changed or improved cognition among patients with MDD or OCD. However, some evidence indicated verbal fluency declined among patients with PD and essential tremor. In AD there was limited evidence supporting the use of DBS to slow cognitive decline. Ablative techniques involve surgically creating focal lesions in the brain. Some examples of lesional techniques include radiofrequency ablation, Gamma Knife radiosurgery, and magnetic-resonance-guided focused ultrasound. Ablative techniques are not associated with substantial impairments to cognition among patients with MDD, OCD, PD, and essential tremor. However, the risk for post-operative cognitive decline was lower after magnetic resonance-guided focused ultrasound relative to other approaches. Review authors concluded, “Overall, clinicians and patients can be reassured that the neuromodulation therapies used to treat the psychiatric and neurological conditions discussed in this Review do not generally cause cognitive impairment.” The review authors noted that cognitive effects were often assessed as a secondary outcome which may have decreased the power for the studies to detect cognitive changes. In addition, many studies had small sample sizes, lacked a control group, and did not have long-term follow-up data to evaluate outcomes after a sufficient amount of time. Note: This article originally appeared on Psychiatry Advisor