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  • The DEA Plans to Reschedule Marijuana: What Happens Next?

    The US Drug Enforcement Agency (DEA) is moving forward with plans to move marijuana from a Schedule I to a Schedule III controlled substance under the Controlled Substance Act (CSA), the US Department of Justice officials announced this week. First reported by the Associated Press and since confirmed by Medscape Medical News through a US Department of Justice spokesperson, the news made international headlines. Despite the media splash, the final rule is still months away. How did we get here? What happens next? What impact might rescheduling have on clinicians, patients, researchers, and the medical cannabis industry? Why Reschedule? Why Now? The DEA's decision is based on a 2023 determination from the US Food and Drug Administration (FDA) that marijuana has a legitimate medical use and should be moved to Schedule III. DEA defines Schedule I drugs as those with no currently accepted medical use and a high potential for abuse. That class includes heroin, LSD, and ecstasy. Schedule III drugs have a moderate to low potential for physical and psychological dependence and have a currently accepted medical use. This class includes ketamine, acetaminophen with codeine, and buprenorphine. Even though the manufacturing, distribution, sale, and use of marijuana has long violated federal law, 38 states and Washington, DC, have legalized medical cannabis, and 24 states and DC have legalized its recreational use. Congress has allowed states leeway for the distribution and use of medical marijuana, and current and previous presidential administrations have chosen not to aggressively pursue prosecution of state-allowed marijuana use, the Congressional Research Service (CRS) reports. Pressure to address the conflict between federal and state laws and an increasing interest in drug development of cannabis and cannabis-derived products probably contributed to the DEA's decision, said Stephen Strakowski, MD, professor, and vice chair of psychiatry at Indiana University in Indianapolis, and professor and associate vice president at University of Texas in Austin. "The trend toward legalization is everywhere and even though nationally the feds in this instance are lagging the states, the pressure to legalize has been intense for 50 years and it's not surprising that the DEA is finally following that lead," Strakowski told Medscape Medical News. How Does Rescheduling Work? What's the Timeline? The DEA will submit a formal rule proposing that marijuana be moved from Schedule I to Schedule III to the White House Office of Management and Budget. The timing of the submission is unclear. Once the proposed rule is posted to the Federal Register, there will be a public comment period, which usually lasts 30-60 days. "This will likely generate a lot of public comment," Robert Mikos, JD, LaRoche Family Chair in Law at Vanderbilt University Law School in Nashville, told Medscape Medical News. "Then the agency has to go back and wade through those comments and decide if they want to proceed with the rule as proposed or modify it." A final rule will probably be posted before the end of the current presidential term in January, Mikos said. While a lawsuit blocking its implementation is possible, there is a "low chance that a court would block this," he added. How Will Rescheduling Affect Medical Marijuana? For medical marijuana, changing the drug to a Schedule III means that it can legally be prescribed but only in states that have legalized medical cannabis, Mikos said. "If you're a patient in a state with a medical marijuana law and your physician gives you a prescription for medical marijuana and you possess it, you will no longer be guilty of a federal crime," he said. Rescheduling could also benefit patients who receive care through the Veterans Administration (VA), Mikos said. For several years, the VA has had a policy that blocked clinicians from prescribing medical marijuana because as a Schedule I drug, it was determined to have no accepted medical use. "It's possible the VA may drop that policy once the drug gets rescheduled. If you're in a medical marijuana state, if you're a VA patient, and you don't want to spend the extra money to go outside that system, this will have meaningful impact on their lives," Mikos said. But what about patients living in states that have not legalized medical cannabis? "You still wouldn't be committing a federal crime, but you could be violating state law," Mikos said. "That's a much more salient consideration because if you look at who goes after individuals who possess small amounts of drugs, the state handles 99% of those cases." The manufacture, distribution, and possession of recreational marijuana would remain illegal under federal law. What Does It Mean for Medical Marijuana Dispensaries? Though rescheduling makes it legal for clinicians to prescribe medical marijuana and for patients to use it, the actual sale of the drug will remain illegal under federal law because rescheduling only changes prescribing under the CSA, Mikos said. "If you're a dispensary and you sell it, even if it's to somebody who's got a prescription, you're still probably violating the Food, Drug and Cosmetics Act. Rescheduling doesn't change that," he said. "Even assuming the DEA follows through with this and it doesn't come undone at some future date, the industry is still going struggle to comply with the Controlled Substances Act post-rescheduling because that statute is going to continue to impose a number of regulations on the industry," Mikos added. However, rescheduling would change the tax status of the estimated 12,000-15,000 state-licensed cannabis dispensaries in the United States, allowing access to certain tax deductions that are unavailable to sales involving Schedule I controlled substances, James Daily, JD, MS, with Center for Empirical Research in the Law at Washington University School of Law in St. Louis, told Medscape Medical News. "Many cannabis businesses do in fact pay federal taxes, but the inability to take any federal tax credits or deductions means that their effective tax rate is much higher than it would otherwise be," Daily said. Although new federal tax deductions would likely available to cannabis businesses if marijuana were rescheduled to Schedule III, "their business would still be in violation of federal law," Daily said. "This creates a further tension between state and federal law, which could be resolved by further legalization or it could be resolved by extending the prohibition on tax deductions to include cannabis and not just Schedule I and II drugs," he added. Will Rescheduling Make It Easier to Conduct Cannabis-Related Research? Research on medical cannabis has been stymied by FDA and DEA regulations regarding the study of Schedule I controlled substances. Although rescheduling could lift that barrier, other challenges would remain. "Schedule III drugs can be more easily researched, but it's unclear if, for example, a clinical trial could lawfully obtain the cannabis from a dispensary or if they would still have to go through the one legal federal supplier of cannabis," Daily said. The FDA reports having received more than 800 investigational new drug applications for and pre-investigational new drug applications related to cannabis and cannabis-derived products since the 1970s, the agency reports. To date, the FDA has not approved any marketing drug applications for cannabis for the treatment of any disease or condition. In January 2023, the agency published updated guidelines for researchers and sponsors interested in developing drugs containing cannabis or cannabis-derived compounds. It's unclear whether those guidelines would be updated if the rescheduling moves forward. Does Rescheduling Marijuana Pose Any Risk? In its report to the DEA that marijuana be rescheduled, the FDA was careful to note that the agency's recommendation is "not meant to imply that safety and effectiveness have been established for marijuana that would support FDA approval of a marijuana drug product for a particular indication." That's a notation that clinicians and patients should take to heart, Strakowski said. "It's important to remind people that Schedule III drugs, by definition, have addiction and other side effect risks," he said. "The celebrity marketing that sits behind a lot of this is incompletely informed. It's portrayed as fun and harmless in almost every movie and conversation you see, and we know that's not true." Previous studies have linked cannabis to increased risk for mania, anxiety disorders, and schizophrenia. "It is increasingly clear that marijuana use is linked to poor outcomes in people who struggle with mental illness," Strakowski said. "We have no evidence that it can help you but there is evidence that it can harm you." Strakowski likens cannabis use to alcohol, which is a known depressant that is associated with worse outcomes in people with mental illness. "I think with cannabis, we don't know enough about it yet, but we do know that it does have some anxiety risks," he said. "The risks in people with mental illness are simply different than in people who don't have mental illness." Strakowski, Mikos, and Daily report no relevant disclosures. Kelli Whitlock Burton is an assistant managing editor for Medscape who covers neurology and psychiatry. Note: This article originally appeared on Medscape

  • Top Predictors of Substance Initiation in Youth Flagged

    By age 12 years, more than 14% of children have tried alcohol or tobacco, and religion, race, and income are the top predictors beginning to use these and other substances, new research suggests. Aside from sociodemographic parameters, risk factors for substance use initiation include prenatal exposure to substances, peer use of alcohol and nicotine, and problematic school behavior, among other things, the study showed. The results show certain modifiable risk factors may play a role in preventing youth from starting to use substances, study author ReJoyce Green, PhD, research assistant professor, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, told Medscape Medical News. "If we're designing, say, a prevention program or an early intervention program, these are things that could make a difference, so let's make sure we're bringing them into the conversation." The findings were presented on May 6 at the American Psychiatric Association (APA) 2024 Annual Meeting and published online in the American Journal of Psychiatry. Critical Risk Factors Use of alcohol, tobacco, and cannabis often begins during adolescence. One recent survey showed that 23% of 13-year-olds reported using alcohol, 17% reported vaping nicotine, and 8% reported vaping cannabis. Other research links younger age at substance use initiation to a more rapid transition to substance use disorders and higher rates of psychiatric disorders. Previous studies examining predictors of substance use initiation in the Adolescent Brain Cognitive Development (ABCD) Study dataset focused primarily on self-reported measures, but the current study also looked at models that include hormones and neurocognitive factors as well as neuroimaging. This study included 6829, 9- and 10-year-olds from the ABCD Study who had never tried substances and were followed for 3 years. A sophisticated statistical approach was used to examine 420 variables as predictors of substance use initiation. Initiation was defined as trying any nonprescribed substance by age 12 years. " That's including a single sip of alcohol or puff of a cigarette," said Green. In addition to alcohol, nicotine, and cannabis, researchers looked at initiation of synthetic cannabinoids, cocaine, methamphetamine, and ketamine, among other substances. Self-reported measures included demographic characteristics, self and peer involvement with substance use, parenting behaviors, mental and physical health, and culture and environmental factors. The analytical approach used machine-learning algorithms to compare the ability of domains to identify the most critical risk factors. Magnitudes of coefficients were used to assess variable importance, with positive coefficients indicating greater likelihood of substance initiation and negative coefficients indicating lower likelihood of initiation. By age 12 years, 14.4% of the children studied reported substance initiation. Alcohol was the substance most commonly initiated (365 individuals), followed by nicotine (94 individuals) and cannabis (40 individuals), with few or no children initiating other substances. Both those who did and did not initiate substances were similarly aged, and most participants identified as White and non-Hispanic. But the substance-use group had a lower percentage of girls and higher percentage of White participants compared with the no-substance-use group. The model with only self-reported data had similar accuracy in predicting substance use initiation (area under the curve [AUC], 0.67) as models that added resource-intensive measures such as neurocognitive tests and hormones (AUC, 0.67) and neuroimaging (AUC, 0.66). Religious Predictors The strongest predictors of substance use initiation were related to religion: Youths whose parents reported a religious preference for Mormonism were less likely to initiate substance use (coefficient, -0.87), whereas youths whose parents reported a religious preference for Judaism were more likely to initiate substance use (coefficient, 0.32). The third top predictor was race: Black youths were less likely to initiate substance use (coefficient, -0.32). This was followed by youths whose parents reported a religious preference for Islam who were also less likely to initiate substance use (coefficient, -0.25). The research examined over 15 different religious categories, "so we really tried to be expansive," noted Green. It's unclear why some religions appeared to have a protective impact when it comes to substance use initiation whereas others have the opposite effect. Future research could perhaps identify which components of religiosity affect substance use initiation. If so, these aspects could be developed and incorporated into prevention and intervention programs, said Green. Next on the list of most important predictors was being a part of a household with an income of $12,000-$15,999; these youths were less likely to initiate substance use (coefficient, 0.22). Within the culture and environment domain, a history of detention or suspension was a top predictor of substance use initiation (coefficient, 0.20). Prenatal exposure to substance use was also a robust predictor in the physical health category (coefficient, 0.15). Other predictors included: parents with less than a high school degree or GED (coefficient, -0.14), substance use availability (coefficient, 0.12), and age at baseline (coefficient, 0.12). The study also showed that better cognitive functioning in selected domains (eg, cognitive control, attention, and language ability) is associated with a greater likelihood of substance use initiation. Shaping Future Prevention Applying these findings in clinical settings could help tailor prevention and early intervention efforts, said the authors. It might be prudent to allocate resources to collecting data related to self-, peer-, and familial-related factors, "which were more informative in predicting substance use initiation during late childhood and early adolescence in the present study," they wrote. Researchers will continue to track these children through to a 10-year follow-up, said Green. "I'm really curious to see if the factors we found when they were 12 and 13, such as those related to peers and family, still hold when they're ages 17 and 18, because there's going to be a huge amount of brain development that's happening throughout this phase." The group that initiated substance use and the group that didn't initiate substance use were not totally balanced, and sample sizes for some religious categories were small. Another study limitation was that the analytic approach didn't account for multilevel data within the context of site and families. Commenting for Medscape Medical News, Kathleen Brady, MD, PhD, distinguished university professor and director, South Carolina Clinical and Translational Research Institute, Medical University of South Carolina, said that the study is "critical and complex." This, she said, is especially true as cannabis has become more accessible and potent, and as the federal government reportedly considers reclassifying it from a Schedule I drug (which includes highly dangerous, addictive substances with no medical use) to a Schedule III drug (which can be prescribed as a medication). "The part that is the most frightening to me is the long-lasting effects that can happen when young people start using high-potency marijuana at an early age," said Brady. "So, any information that we can give to parents, to teachers, to the public, and to doctors is important." She's looking forward to getting more "incredibly important" information on substance use initiation as the study progresses and the teens get older. The study received support from the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse. Note: This article originally appeared on Medscape

  • DEA Moves to Reclassify Marijuana as a Schedule III Drug

    Keypoint: The proposed change acknowledges the medical applications of marijuana. The Associated Press has reported that the US Drug Enforcement Administration (DEA) is planning to reclassify marijuana to a less dangerous drug category. The proposed change acknowledges the medical applications of marijuana and suggests that the drug poses a lower risk of abuse compared with certain other controlled substances. Pending review by the White House Office of Management and Budget, the suggested reclassification would shift marijuana from its current Schedule I classification, alongside substances like heroin and lysergic acid diethylamide (LSD), to Schedule III, placing it alongside medications such as ketamine and certain anabolic steroids. However, this reclassification would not entail full legalization for recreational use. “In a long overdue policy change, the DEA has announced its plan to reclassify marijuana as a lower-risk drug,” John J. Miller, MD, told Psychiatric Times®. “The next required step is approval of this change by the White House Office of Management and Budget. Unfortunately, if approved, this policy change does not go far enough. It will not legalize marijuana federally—rather, improve access and parameters of use in states where it is already legal.” Miller is medical director at Brain Health in Exeter, New Hampshire; editor in chief of Psychiatric Times; a staff psychiatrist at Seacoast Mental Health Center in Exeter; and a consulting psychiatrist at Insight Meditation Society in Barre, Massachusetts. Marijuana is currently legal for recreational use in 24 US states and for medical use in 14 US states.2 Georgia will also soon become the first state to allow the sale of medical marijuana products in independent pharmacies, with more than 100 more pharmacies applying to participate.3 Public opinion toward legalization of marijuana, for both medical and recreational purposes, has also shifted, with a recent Gallup poll indicating that a record 70% of adults are in favor of legalization.4 Part of this shift has to do with the significant amount of information publicly available claiming the efficacy of marijuana for a wide variety of uses.3 “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 US Food and Drug Administration (FDA)-approved indications, its limited evidence, and the poorly regulated products available in marijuana dispensaries,” Yi-lang Tang, MD, PhD; Elizabeth McCord, MD; and Karen Drexler, MD, recently wrote in Psychiatric Times.3 The authors—who are all affiliated with the Department of Psychiatry and Behavioral Sciences at Emory University in Atlanta, Georgia—emphasized that medical marijuana and medicine are not the same thing. Variations in state laws regarding qualifying conditions, a lack of scientific consensus on efficacy and safety due to a lack of controlled trials, and inconsistent quality control in the production of marijuana all suggest a need for clinicians to educate the public about medical marijuana and its potential risks and benefits.3 According to Miller, further distinction in the proposed reclassification of marijuana announced today may also help with these efforts. “As we have opined in Psychiatric Times over the years, it would be more beneficial and scientifically accurate to redefine this policy for tetrahydrocannabinol (THC), as cannabidiol (CBD) is already a legal and unscheduled drug federally,” Miller told Psychiatric Times. “The terms marijuana and cannabis are vague, and they include plant products that contain over 100 different cannabinoids, most of which are not well characterized. THC and CBD are the best studied and have dramatically different clinical effects and pharmacologies.” Note: This article originally appeared on Psychiatric Times

  • ADHD, Stimulant Use, and Failure to Thrive in Pediatric Patients

    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

  • The Failed Concept of Treatment Resistance

    CONFERENCE REPORTER According to some estimates, about 20% to 60% of psychiatric diagnoses eventually become labeled “treatment resistant,” yet psychiatry seems to lack a consensus on what “treatment resistance” means, including clear criteria, H. Paul Putman III, MD, told Psychiatric Times in an exclusive interview. Putman, a Distinguished Life Fellow of the American Psychiatric Association and a Fellow and former Laughlin Fellow of the American College of Psychiatrists (ACP), led the session “Encountering Treatment Resistance and Finding Solutions” at the 2024 American Psychiatric Association Annual Meeting in New York City, May 3-8, 2024.1 In his presentation, he explored the concept of treatment resistance and how these cases may actually be a result of treatment failure. The goal, he noted, is to help patients, including those whose initial outcomes are disappointing. Putnam said the field needs to shift its focus. Part of that, he told Psychiatric Times, is remembering that clinicians are humans who make mistakes. Before leveraging the term treatment resistant, Putnam, it is important to examine and rethink the facts. “We have innate biases that distort our clinical reasoning,” he explained. “We are not as aware of them all the time as we need to be, and I include myself.” He explained clinicians need to use metacognition to avoid being on autopilot, which should result in less treatment failures for patients. Metacognition should help clinicians consider if the tools they are using as part of the treatment strategy are the most appropriate tools for each particular case. Similarly, it should allow clinicians to learn more tools and find new ways to apply those tools during diagnosis and treatment planning. Moreover, this approach encourages clinicians to go back and reexamine the problem from the beginning when there is a treatment failure, so they can better understand what data is missing and how to obtain that data. “This creative iteration needs to go on over and over again until you get satisfactory results for your patients,” he explained. Note: This article originally appeared on Psychiatric Times

  • Suicide and Other Deaths From Unnatural Causes in Bipolar Disorder

    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®

  • Benzodiazepines: The Considerable Risk of Abuse & How to Taper

    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

  • Customized Video Games Promising for ADHD, Depression, in Kids

    Targeted video games could help reduce symptoms of attention-deficit/hyperactivity disorder (ADHD) and depression in children and adolescents, results of a new review and meta-analysis suggested. Although the video game–based or "gamified" digital mental health interventions (DMHIs) were associated with modest improvements in ADHD symptoms and depression, investigators found no significant benefit in the treatment of anxiety. "The studies are showing these video games really do work, at least for ADHD and depression but maybe not for anxiety," Barry Bryant, MD, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, told Medscape Medical News. "The results may assist clinicians as they make recommendations to patients and parents regarding the efficacy of using these video games to treat mental health conditions." The findings were presented on May 6, 2024, at the American Psychiatric Association (APA) 2024 Annual Meeting. A Major Problem Childhood mental illness is a "big problem," with about 20% of kids facing some mental health challenge such as ADHD, anxiety, or depression, said Bryant. Unfortunately, these youngsters typically have to wait a while to see a provider, he added. DMHIs may be an option to consider in the meantime to help meet the increasing demand for treatment, said Bryant. Gamified DMHIs are like other video games, in that players advance in levels on digital platforms and are rewarded for progress. But they're created specifically to target certain mental health conditions. An ADHD game, for example, might involve users completing activities that require an increasing degree of attention. Games focused on depression might incorporate mindfulness and meditation practices or cognitive behavioral elements. Experts in child psychiatry are involved in developing such games along with professionals in business and video game technology, said Bryant. But the question is do these games really work? Effective for ADHD, Depression Investigators reviewed nearly 30 randomized controlled trials of gamified DMHIs as a treatment for anxiety, depression, and/or ADHD in people younger than 18 years that were published from January 1, 1990, to April 7, 2023. The trials tested a wide variety of gamified DMHIs that fit the inclusion criteria: A control condition, a digital game intervention, sufficient data to calculate effect size, and available in English. A meta-analysis was performed to examine the therapeutic effects of the gamified DMHIs for ADHD, depression, and anxiety. For all studies, the active treatment was compared with the control condition using Hedges's g to measure effect size and 95% CIs. Bryant noted there was significant heterogeneity of therapeutic effects between the studies and their corresponding gamified interventions. The study found gamified DMHIs had a modest therapeutic effect for treating ADHD (pooled g = 0.280; P = .005) and depression (pooled g = 0.279; P = .005) in children and adolescents. But games targeting anxiety didn't seem to have the same positive impact (pooled g = 0.074; P = .197). The results suggest the games "show potential and promise" for certain mental health conditions and could offer a "bridge" to accessing more traditional therapies, Bryant said. "Maybe this is something that can help these children until they can get to see a psychiatrist, or it could be part of a comprehensive treatment plan," he said. The goal is to "make something that kids want to play and engage with" especially if they're reluctant to sit in a therapist's office. The results provide clinicians with information they can actually use in their practices, said Bryant, adding that his team hopes to get their study published. Gaining Traction Commenting for Medscape Medical News, James Sherer, MD, medical director, Addiction Psychiatry, Overlook Medical Center, Atlantic Health System, said the study shows the literature supports video games, and these games "are gaining traction" in the field. He noted the app for one such game, EndeavorRx, was one of the first to be approved by the US Food and Drug Administration to treat ADHD in young people aged 8-17 years. EndeavorRx challenges players to chase mystic creatures, race through different worlds, and use "boosts" to problem-solve while building their own universe, according to the company website. By being incentivized to engage in certain activities, "there's a level of executive functioning that's being exercised and the idea is to do that repetitively," said Sherer. Users and their parents report improved ADHD symptoms after playing the game. One of the studies included in the review found 73% of children who played EndeavorRx reported improvement in their attention. The company says there have been no serious adverse events seen in any clinical trial of EndeavorRx. Sherer noted many child psychiatrists play some sort of video game with their young patients who may be on the autism spectrum or have a learning disability. "That may be one of the few ways to communicate with and effectively bond with the patient," he said. Despite their reputation of being violent and associated with "toxic subcultures," video games can do a lot of good and be "restorative" for patients of all ages, Sherer added. No relevant conflicts of interest were disclosed. Note: This article originally appeared on Medscape

  • Frequent Vaping in Teens Tied to Higher Toxic Metal Exposure

    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

  • Family History of TRD Increases Risk for Suicide, Antidepressant Resistance

    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

  • Efficacy of Antipsychotics for First-Episode Psychosis and Cannabis Use Disorder

    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

  • Incorporating Evidence-Based Cognitive Health Services In Large Systems of Care

    Keypoint: OnTrackNY (OTNY) piloted its Cognitive Health Toolkit to implement cognitive health services in large systems of care. The implementation of cognitive health services in large systems of care is possible with the help of training programs, quality assurance monitoring, and improvement activities, according to new research published in Schizophrenia Bulletin. Although a wealth of research indicates a critical need for improved cognitive support services, there have been relatively few large-scale efforts that systematically address cognitive health needs in systems of care. To address this gap between research and practice, the current study aimed to evaluate and outline the necessary adaptations for effective implementation of cognitive health services in routine clinical settings within larger systems of care. Investigators evaluated the implementation of cognitive health services within the OnTrackNY (OTNY) network of clinics that deliver Coordinated Specialty Care programs in New York state. OnTrack Central coordinated with local agencies and team leaders to govern the implementation process, and a Cognitive Health Toolkit was developed to facilitate the systematic assessment and integration of cognitive health interventions. The investigators evaluated the program via quality assurance monitoring from 2019 through 2022. The primary outcomes of interest included the use of the cognitive health screening tool, rates of self-reported and/or clinician-reported cognitive health needs, and participant interest in addressing cognitive health. OnTrack Central provided 18 OTNY teams with the Cognitive Health Toolkit and these teams received training on screening participants for cognitive health needs and providing participants with relevant psychoeducation and skills training. In the first full year of implementation, the use of cognitive health screening tools was 53.9% – although these rates varied from 8.3% to 100% across the OTNY network. Among participants who were screened in 2019, 95.5% were identified via self- report and/or clinician-report, with clinicians identifying cognitive health needs (68.4%) more frequently than participants (52.4%). Of those who were referred for the service based on an identified cognitive health need, 92.2% received a standardized neurocognitive assessment battery and 78.4% initiated cognitive remediation sessions. The investigators noted that before the development and implementation of the Cognitive Health Toolkit, there was significant variability in the methods used to assess cognitive health needs across OTNY teams, and the methods used were not always evidence-based. Additionally, the investigators found that the organizational infrastructure of OTNY facilitated the implementation of a standardized approach for cognitive health services throughout the larger system. The investigators concluded, “Our experience speaks to the need for a flexible, person-centered service model and a comprehen­sive, responsive system of implementation support to en­able the start-up, evolution, and improvement of cognitive health services within large systems of care.” Note: This article originally appeared on Psychiatry Advisor

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