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Keypoint: A recent study analyzed longitudinal data of patients with schizophrenia or major depressive disorder to rank treatment regimens in terms of weight gain, adverse effects, and response to treatment. Individuals with psychiatric diagnoses are especially vulnerable to experiencing obesity or rapid, undesirable weight gain due to psychotropic medications.1 Mental health treatment strategies often include polypharmacy; however, previous research on drug-induced weight gain mainly focused on monotherapy and is therefore not applicable. Investigators analyzed longitudinal data of 832 inpatients with ICD-10 diagnoses of either schizophrenia (n = 282) or major depressive disorder (n = 550) to rank treatment regimens in terms of weight gain, adverse effects, and response to treatment. These data were complemented by data from 3180 students aged 18 to 22 years, which the investigators used to identify factors for early detection and prevention of obesity and mental health disorders. Following 3 weeks of treatment, 47.7% of patients with schizophrenia and 54.9% of patients with major depressive disorder showed 2 kg or more in weight gain.2 Starting weight (r = 0.115), concurrent medications (r = 0.176), and increased appetite (r = 0.275) were major predictive factors. When investigators compared monotherapy (n = 409) with polypharmacy (n = 399), they found significant issues associated with polypharmacy, including increased weight gain (P = .0005), more severe adverse effects (P = .0011), and lower response rates (schizophrenia: P = .0008; major depressive disorder: P = .0101). The student data established that obesity often begins early in life, is interconnected with personality traits such as “defeatism,” and increases the risk of developing psychosomatic disturbances, mental health problems, or somatic illnesses. Results also demonstrated ways to successfully counteract weight gain during the early stages of treatment, even though the data did not create a comprehensive and applicable model of said weight gain. The investigators listed 8 questions for their research project to address, which could then be translated into clinical practice, including the following: To what extent is obesity more prevalent among psychiatric patients compared with the general population? To what extent do psychotropic drugs induce unwanted weight gain? What are the differences in drug-induced weight gain between patients with schizophrenia (antipsychotics) and patients with major depressive disorder (antidepressants)? What are the differences between monotherapy and polypharmacy for drug-induced weight gain? What is the severity of the adverse effects that cooccur with drug-induced weight gain? What factors might predict drug-induced weight gain? To what extent does obesity start developing in early life? What factors might influence obesity in early life? This study identified several major factors that contribute to drug-induced unwanted weight gain, thereby suggesting clinically easily realizable ways of avoiding such weight gain. On average, patients receiving treatment via polypharmacy took 4.19 ± 1.92 medications, consisting of 3.08 ± 1.81 psychotropic drugs, 0.74 ± 1.15 medications that alleviate adverse effects, and 0.37 ± 0.83 other somatic medications. Also of interest was the comparison between monotherapy (n = 409) and polypharmacy (n = 399), as far more patients with major depressive disorder (56.0%) were assigned to a polypharmacy regimen than patients with schizophrenia. (32.3%). Upon performing correlation analyses, investigators found several significant interrelations between weight gain and variables that reached significance in an explorative generalized linear regression model: (1) starting weight (r = 0.11469; P = .0117); (2) number of concurrent psychotropic drugs (r = 0.16553; P = .0002); and (3) a treatment-induced “increased appetite” from the treatment outset (r = 0.27525; P < .0001). Male patients showed higher average weight gains than female patients, although the differences did not reach statistical significance. Furthermore, there was a strong correlation between unwanted weight gain and the number of concurrent psychotropic medications (r = 0.16553; P = .0002). When comparing psychotherapy to pharmacotherapy, the investigators noted that patients who received psychotherapy alone experienced only minor adverse effects (n = 24), followed by patients receiving monotherapy (n = 409); however, patients receiving polypharmacy reported more severe adverse effects (n = 399). They noted the significant difference between monotherapy and polypharmacy (P = .0011). Additionally, the data of 3180 students aged 18 to 22 years made it clear that overweight and obesity often begin early in life among those affected, and are interconnected with personality traits, while increasing the risk of developing psychosomatic disturbances, mental health problems, or somatic illnesses. The student data also cleared the way for applications aiming at the early detection and prevention of overweight and obesity. “Given these results, we think psychiatry has developed to a significant extent in the wrong direction over the past 15 years. In particular, it seems to be time for psychiatry to reconsider its treatment strategies, which are far too one-sidedly fixated on psychopharmacology and pay far too little attention to alternative options, especially in mild cases,” the study authors wrote.1 “Most importantly, the polypharmacy approach to treating [patients with major depressive disorder] or [schizophrenia] can in no way—not even rudimentarily—solve the problem that there is no causal therapy in psychiatry.” Note: This article originally appeared on Psychiatric Times

Welcome everyone. I'm Dr. John White. I'm the chief medical officer at WebMD. Does your biologic sex impact your health? Does it have any play in how you're diagnosed, how you're treated in terms of what symptoms you have? Of course it does. We all know that. But that's not something that many people believed 5, 10 years ago, certainly not 20 years ago. And it was only because of leaders like my guest today, Phyllis Greenberger, who really championed the need for research on women's health. She has a new book out, which I love. It's called Sex Cells: the Fight to Overcome Bias and Discrimination in Women's Healthcare. Please welcome my very good friend, Phyllis Greenberger. Thank you. Phyllis. It's great to see you today. It's great to see you as well. Now, you and I have been talking about this for easily 2 decades. At least. And some people think, oh, of course it makes sense. Although I saw you disagreeing that not everyone still believes that. But what has been that journey? Why has it been so hard to make people understand, as you point out early on in your book, women are not smaller men? I think the basic reason was that it was just believed that men and women were the same except for their reproductive organs. So minus the reproductive organs, whether it was a device, a diagnostic, or therapeutic, if it was used and successful on a male, that it would be successful on a female. We're really very far from understanding the differences, and there's still a lot of distrust and disbelief and ignorance about it. And so there's still a long way to go. But you talk about that in the book, that there's still a long way to go. Why is that? What's the biggest obstacle? Is it just misinformation, lack of information? People don't understand the science? There's still resistance in some areas. Why is that? I think it's misinformation, and I gave a presentation, I don't know how many years ago, at least 20 years ago, about the curriculum. And at the time, there was no women's health in the curriculum. It was health. So if it was on cardiovascular issues or on osteoporosis, it was sort of the basic. And at the time, there would maybe be one woman whose job was women's health, and she'd have an office, and otherwise there was nothing. And maybe they talked about breast cancer, who knows. But I spoke to someone just the other day, in view of all the attention that the book is getting now, whether that's changed, whether it's necessary and required. And she said it's not. So, it's not necessarily on the curriculum of all research and medical institutions, and even if women's health, quote unquote, is on the curriculum, it doesn't mean that they're really looking at sex differences. And the difference is obvious. I mean, gender is really, it's a social construct, but biological sex is how disease occurs and develops. And so if you're not looking, and because there's so little research now on sex differences that I don't even know, I mean, how much you could actually teach. So what needs to change? This book is a manifesto in many ways in how we need to include women; we need to make research more inclusive of everyone. But we're not there yet. So what needs to change, Phyllis? During this whole saga of trying to get people to listen to me and to the society, we really started out just looking at clinical trials and that, as you mentioned, I mean, there are issues in rural communities. There's travel issues for women and child care. There's a lot of disbelief or fear of clinical trials in some ethnicities. I do think, going to the future, that technology can help that. I mean, if people have broadband, which of course is also an issue in rural areas. What could women do today? What should women listeners hear and then be doing? Should they be saying something to their doctor? Should they be asking specific questions? When they interact with the health care system, how can they make sure they're getting the best care that's appropriate for them when we know that sex cells matter? Well, that's a good question. It depends on, frankly, if your doctor is aware of this, if he or she has learned anything about this in school, which, I had already said, we're not sure about that because research is still ongoing and there's so much we don't know. So I mean, you used to think, or I used to think, that you go to, you want a physician who's older and more experienced. But now I think you should be going to a physician who's younger and hopefully has learned about this, because the physicians that were educated years ago and have been practicing for 20, 30 years, I don't know how much they know about this, whether they're even aware of it. Phyllis, you are a woman of action. You've lived in the DC area. You have championed legislative reforms, executive agendas. What do you want done now? What needs to be changed today? The curriculum is going to take time, but what else needs to change? That's a good question. I mean, if curriculum is going to take a while and you can ask your doctor if he prescribes the medication, whether it's been tested on women, but then if it hasn't been tested on women, but it's the only thing that there is for your condition, I mean, so it's very difficult. The Biden administration, as you know, just allocated a hundred million dollars for women's health research. What do you hope to accomplish with this book? Well, what I'm hoping is that I spoke to someone at AMWA and I'm hoping – and AMWA is an association for women medical students. And I'm hoping that's the audience. The audience needs to be. I mean, obviously everybody that I know that's not a doctor that's read it, found it fascinating and didn't know a lot of the stuff that was in it. So I think it's an interesting book anyway, and I think women should be aware of it. But really I think it needs to be for medical students. And to your credit, you built the Society for Women's Health Research into a powerful force in Washington under your tenure in really promoting the need for Office of Women's Health and Research in general. The book is entitled Sex Cells, the Fight to Overcome Bias and Discrimination in Women's Healthcare. Phyllis Greenberger, thank you so much for all that you've done for women's health, for women's research. We wouldn't be where we are today if it wasn't for you. So thanks. Thank you very much, John. Thank you. I appreciate the opportunity. This interview originally appeared on WebMD on May 23, 2024 Note: This article originally appeared on Medscape

Keypoint:Polypharmacy is often overlooked in patients with significant traumatic brain injury. How can you best manage medication in these patients? The issue of polypharmacy is often overlooked in patients with significant traumatic brain injury (TBI). In the acute setting—which includes the emergency department, critical care unit, and hospital floor—attention is appropriately fixed on survival and medical stabilization. To that end, interventions range from neurosurgical to pharmacological. In a typical severe TBI scenario, it is not unusual for a patient to undergo multiple surgical procedures (eg, craniotomy/craniectomy, ventricular drains, various orthopedic procedures to address polytrauma, tracheostomy, gastrostomy tube placement). The science behind the acute management of TBI is evolving, and any intervention that improves survival and reduces long-term morbidity is worthwhile. But as patients recover, many of the pharmacological interventions become counterproductive and should be discontinued. TBI is increasingly recognized as a chronic disease with chronic impairments. Therefore, the majority of care for the patient with TBI occurs post hospital. This care is often highly fragmented and many opportunities to reduce medications and avoid polypharmacy and comorbidity can be missed. Many categories of medication frequently used in patients with TBI can contribute to polypharmacy. Some medications sedate and cloud the sensorium, potentially limiting recovery. This group includes antipsychotics, anxiolytics, antiepileptics, and opiates. Another group includes preventive medications, whether for deep venous thrombosis (DVT) and pulmonary embolism (PE), seizures, or headaches. Yet another group might be referred to as convenience medication; for example, as-needed antiemetics. There are also medications directed at specific and frequent associated conditions such as syndrome of inappropriate antidiuretic hormone secretion (SIADH), cerebral salt wasting, autonomic dysfunction, neurogenic bowel/bladder, and so on. This article will attempt to address each medication briefly. What is important for clinical practitioners to know is that every successive evaluation is an opportunity to reexamine the medication list for necessity. Some of the most problematic contributors to polypharmacy are the most common: sedating medications. Antipsychotics, typically used in acute settings to manage behavioral complications of TBI, or in rare cases actual psychosis, are generally detrimental to TBI recovery in the long term, unless the patient is diagnosed with psychosis. Similarly, benzodiazepines are generally detrimental unless used for very specific and time-limited purposes such as obtaining diagnostics, performing procedures, and the like. In addition, like opiates, the addictive potential of these medications in a patient with TBI and associated impulsivity is high. Opiate medications are unfortunately frequently necessary in patients with TBI, at least temporarily, as there is frequently associated polytrauma. These medications carry known and varied risks as mentioned, including addictive potential. Awareness of the individual risks of each of these medications, as well as the cumulative effects of polypharmacy involving multiple agents, is paramount. Recovery from TBI is already difficult for a patient combating impaired sensation due to impairments in vision, proprioception, balance, spatial awareness, language, vertigo, and so on. Unnecessary sedation from medication does not improve the process. Antiepileptic medication is frequently initiated prophylactically during acute care for any patient who has a TBI with intracranial bleeding, and continued use is appropriate for patients who do experience seizure disorder post TBI. However, in patients without a history of seizure post TBI, guidelines suggest that this is not recommended beyond 7 days.1 Many antiepileptics have significant drug-drug interactions, pharmacokinetic impact, and other adverse effects. Older antiepileptics such as carbamazepine, oxcarbazepine, phenytoin, and phenobarbital have significant effects on cytochrome P450 enzymes. This leads to pharmacokinetic effects and risk for changes in serum drug levels. Valproic acid can similarly affect circulating drug levels through other mechanisms. Newer antiepileptics have less dramatic effect on serum drug levels but many remain hepatically metabolized, and therefore drug levels should be monitored and dosage adjusted. Fortunately, levetiracetam, considered a first-line agent by many for management of epilepsy post TBI, does not frequently alter the serum level of other drugs in clinical practice. In addition to seizure prophylaxis or management, some of these medications are also commonly used for various other purposes in the TBI population, including headache prevention (eg, topiramate), behavioral intervention (eg, lamotrigine, valproic acid), or neurogenic pain management (eg, gabapentin, pregabalin). These can be effective and beneficial, but as patients improve clinically over time, ongoing use should be addressed. Many patients with TBI suffer from immobility as a consequence, whether transiently or long term. In either instance, acute immobility confers risk for DVT/PE, which some patients do experience during their illness.2 Patients are commonly discharged on prophylaxis for treatment of DVT/PE. This may be with either heparin, low molecular weight heparin, warfarin, or one of the novel anticoagulants. All these medications carry their own adverse effect profiles, and many have significant polypharmacy risks due to drug-drug interactions and pharmacokinetic impacts. In cases where a patient’s mobility improves, prophylaxis should be discontinued appropriately. Other individuals with anticipated long-term immobility still do not benefit from prophylaxis indefinitely, because the risk for DVT/PE in this context wanes over time. Appropriate guidelines related to the duration of treatment for DVT or PE should be adhered to, with medication discontinued when appropriate.3 TBI is also frequently associated with other secondary complications. Disorders of homeostasis such as the SIADH or cerebral salt wasting can result in the addition of fluid restriction or the use of salt tabs and/or fludrocortisone. It is not uncommon for this condition to remain unresolved at the time of discharge from the hospital. However, most often this condition will resolve over time with recovery, and these interventions can then be discontinued. Various other medications, used during acute care to manage hypertension, hyperglycemia, nausea/vertigo, and so on, are frequently prescribed at the time of discharge. With patient improvement, these can also unnecessarily contribute to polypharmacy. This list is exhaustive, but the primary objective here is to highlight the beneficial role of a care provider paying close attention during each visit to the medication list and the ongoing indications (or lack thereof). Finally, as patients proceed through the recovery process, still other medications can be added. Antidepressants, headache prevention or abortive medications, antiepileptics, and many others may be clinically indicated, some even permanently. However, in all cases, vigilance on behalf of all treatment providers as to the polypharmacy concerns remains vital.

Keypoint: A more useful measure than BMI or waist circumference? Researchers analyzed the association between weight-adjusted waist index and depressive symptoms. CASE VIGNETTE “Ms Gray” is a 42-year-old Caucasian female with a 15-year history of recurrent, severe major depressive disorder (MDD) with psychotic features. She also has significant symptoms of anxiety. She does not smoke, drink alcohol, or use illicit drugs. She meets the criteria for obesity, with a current body mass index (BMI) of 33. She currently takes a selective serotonin reuptake inhibitor and sees a psychologist for cognitive-behavioral therapy. At an outpatient clinic visit, she reports increased interest in exercise. She says she plans to walk in the morning with a neighbor friend. She asks about the potential beneficial effects of exercise on her depression. As her psychiatrist, how would you respond? Depression is the leading cause of disability worldwide.1 Obesity is a replicated risk factor for the onset of depressive symptoms, with a magnitude of >50%.2 Conventional measures of obesity include BMI and waist circumference (WC). However, BMI does not distinguish between visceral fat and muscle mass; similarly, WC does not distinguish between visceral and subcutaneous fat. Weight-adjusted waist index (WWI) has been proposed as a new index of obesity reflecting central obesity, which standardizes WC to better reflect adiposity and muscularity.3 However, the relationship between WWI and depressive symptoms is unknown. The Current Study Liu and colleagues4 investigated associations between WWI and depressive symptoms in the National Health and Nutrition Examination Survey (NHANES) and made comparisons with traditional obesity indices. NHANES data are freely available in the public domain. Data were included for 32,374 participants from 7 2-year cycles (2005 to 2018). Exclusion criteria were age <20 years, pregnancy, and missing data on WC, weight, and/or depressive symptoms. WWI is calculated as the ratio of WC (in cm) to the square root of weight (in kg) (ie, WWI = WC / √ [Weight]). Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9). Additional covariates included age, sex, race/ethnicity, smoking, diabetes, hypertension, alcohol consumption, household income, education level, lipid panel, WC, BMI, and the poverty rate. Differences in demographic variables by WWI quartiles were investigated with t-tests and chi-square tests. Linear associations between WWI, WC, BMI, and depressive symptoms were analyzed using weighted multiple linear regression and logistic regression. The mean participant age was 50 years, 50% of participants were male, and 43% were non-Hispanic white. The mean WWI was 11.1 ± 0.9. There were 2810 participants (9%) with PHQ-9 scores ≥10, which was used as the definition of depressive symptoms. Higher quartiles of WWI were more likely to be female, non-Hispanic white, Mexican American, and smokers, and to drink more alcohol and have diabetes and hypertension. Higher WWI was also associated with higher total and LDL cholesterol, triglycerides, BMI, and WC, and lower education and HDL cholesterol. In a regression model adjusting for age, sex, race/ethnicity, smoking, diabetes, hypertension, alcohol consumption, household income, education level, lipid panel, and the poverty rate, the WWI (as a continuous measure) was associated with depressive symptoms (OR=1.18, 95% CI 1.05-1.34) more strongly than either BMI or WC (OR=1.01 for both). Participants in the highest (versus lowest) quartile of WWI were almost 1.5 times more likely to have depressive symptoms, after controlling for potential confounders (OR=1.49, 95% CI 1.14-1.96). Subgroup analyses indicated that this association was not moderated by age, sex, race/ethnicity, smoking, diabetes, or hypertension. Study Conclusions The investigators concluded that WWI was robustly associated with depressive symptoms with a significantly higher magnitude than either BMI or WC. Study strengths include the use of a large, nationally representative study sample and consideration of many potential confounding factors. Study limitations include the cross-sectional design (which limits causal inferences), the use of a self-report depression measure, and the absence of information on the duration of depressive symptoms and antidepressant treatments. The Bottom Line The weight-adjusted weight index was a stronger predictor of depressive symptoms than either BMI or WC. The WWI represents a potentially useful measure in clinical practice. Note: This article originally appeared on Psychiatric Times

Consuming highly processed foods may be harmful to the aging brain, independent of other risk factors for adverse neurologic outcomes and adherence to recommended dietary patterns, new research suggests. Observations from a large cohort of adults followed for more than 10 years suggested that eating more ultraprocessed foods (UPFs) may increase the risk for cognitive decline and stroke, while eating more unprocessed or minimally processed foods may lower the risk. "The first key takeaway is that the type of food that we eat matters for brain health, but it's equally important to think about how it's made and handled when thinking about brain health," study investigator W. Taylor Kimberly, MD, PhD, with Massachusetts General Hospital in Boston, told Medscape Medical News. "The second is that it's not just all a bad news story because while increased consumption of ultra-processed foods is associated with a higher risk of cognitive impairment and stroke, unprocessed foods appear to be protective," Kimberly added. The study was published online on May 22 in Neurology. Food Processing Matters UPFs are highly manipulated, low in protein and fiber, and packed with added ingredients, including sugar, fat, and salt. Examples of UPFs are soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hotdogs, and fries. Unprocessed or minimally processed foods include meats such as simple cuts of beef, pork and chicken, and vegetables and fruits. Research has shown associations between high UPF consumption and increased risk for metabolic and neurologic disorders. As reported previously by Medscape Medical News, in the ELSA-Brasil, higher intake of UPFs was significantly associated with a faster rate of decline in executive and global cognitive function. Yet, it's unclear whether the extent of food processing contributes to the risk of adverse neurologic outcomes independent of dietary patterns. Kimberly and colleagues examined the association of food processing levels with the risk for cognitive impairment and stroke in the long-running REGARDS study, a large prospective US cohort of Black and White adults aged 45 years and older. Food processing levels were defined by the NOVA food classification system, which ranges from unprocessed or minimally processed foods (NOVA1) to UPFs (NOVA4). Dietary patterns were characterized based on food frequency questionnaires. In the cognitive impairment cohort, 768 of 14,175 adults without evidence of impairment at baseline who underwent follow-up testing developed cognitive impairment. Diet an Opportunity to Protect Brain Health In multivariable Cox proportional hazards models adjusting for age, sex, high blood pressure, and other factors, a 10% increase in relative intake of UPFs was associated with a 16% higher risk for cognitive impairment (hazard ratio [HR], 1.16). Conversely, a higher intake of unprocessed or minimally processed foods correlated with a 12% lower risk for cognitive impairment (HR, 0.88). In the stroke cohort, 1108 of 20,243 adults without a history of stroke had a stroke during the follow-up. In multivariable Cox models, greater intake of UPFs was associated with an 8% increased risk for stroke (HR, 1.08), while greater intake of unprocessed or minimally processed foods correlated with a 9% lower risk for stroke (HR, 0.91). The effect of UPFs on stroke risk was greater among Black than among White adults (UPF-by-race interaction HR, 1.15). The associations between UPFs and both cognitive impairment and stroke were independent of adherence to the Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet, and the Mediterranean-DASH Intervention for Neurodegenerative Delay diet. These results "highlight the possibility that we have the capacity to maintain our brain health and prevent poor brain health outcomes by focusing on unprocessed foods in the long term," Kimberly said. He cautioned that this was "an observational study and not an interventional study, so we can't say with certainty that substituting ultra-processed foods with unprocessed foods will definitively improve brain health," Kimberly said. "That's a clinical trial question that has not been done but our results certainly are provocative." Consider UPFs in National Guidelines? The coauthors of an accompanying editorial said the "robust" results from Kimberly and colleagues highlight the "significant role of food processing levels and their relationship with adverse neurologic outcomes, independent of conventional dietary patterns." Peipei Gao, MS, with Harvard T.H. Chan School of Public Health, and Zhendong Mei, PhD, with Harvard Medical School, both in Boston, noted that the mechanisms underlying the impact of UPFs on adverse neurologic outcomes "can be attributed not only to their nutritional profiles," including poor nutrient composition and high glycemic load, "but also to the presence of additives including emulsifiers, colorants, sweeteners, and nitrates/nitrites, which have been associated with disruptions in the gut microbial ecosystem and inflammation." "Understanding how food processing levels are associated with human health offers a fresh take on the saying 'you are what you eat,'" wrote Gao and Mei. This new study, they noted, adds to the evidence by highlighting the link between UPFs and brain health, independent of traditional dietary patterns and "raises questions about whether considerations of UPFs should be included in dietary guidelines, as well as national and global public health policies for improving brain health." The editorialists called for large prospective population studies and randomized controlled trials to better understand the link between UPF consumption and brain health. "In addition, mechanistic studies are warranted to identify specific foods, detrimental processes, and additives that play a role in UPFs and their association with neurologic disorders," the editorialists concluded. Note: This article originally appeared on Medscape

For those outside the medical profession, it took a global pandemic to finally understand how pervasive distress and suicide are among medical professionals, particularly surgeons. For James Harrop, MD, it was made real years earlier by a colleague he'd trained alongside and worked with for decades — "one of the best surgeons I've ever seen" who, one day, just wasn't there. Lost in his own work, it wasn't until Harrop, a professor of neurological and orthopedic surgery at Thomas Jefferson University, Philadelphia, read an article in The New England Journal of Medicine and realized his friend Michael Weinstein, MD, MPH, had been profoundly depressed for years and was hospitalized for his own safety. Weinstein recovered and later gave grand rounds at Thomas Jefferson University, where he is an associate professor of surgery in the Acute Care Surgery Division. But the story stuck with Harrop. "I said to Mike afterward, I've known you for 20 years and, retrospectively, going back, I never saw a single sign that you were depressed, sad, or had any issues, and he said to me 'that's because I did everything I could to make sure no one knew I had a problem,'" Harrop said during a talk on physician suicide on May 4 at the recent American Association of Neurological Surgeons (AANS) 2024 Annual Meeting. "And that scared me because we need to help these people, we need to identify who they are." Surgeons at Greater Risk Studies have reported that suicide and suicidal ideation are nearly twice as common among physicians compared with among the general population. Among 9175 physicians surveyed in the 2023 Medscape Physician Suicide Report, 9% had considered suicide, and 1% had attempted it. The average for US adults is 4.9% and 0.5%, respectively. Surgeons are at particularly high risk. A 2011 survey of 7905 US surgeons found that 1 in 16 (6.3%) had considered suicide in the previous year. A post-pandemic survey of more than 600 surgeons and surgical trainees reported that one in seven had suicidal ideation. It's often estimated that between 300 and 400 physicians die by suicide each year in the United States, but exact numbers are not known. Recent updated estimates from the National Violent Death Reporting System put the number at 119 physician suicides annually. Notably, that's no better than data reported more than 50 years ago in the landmark policy paper The Sick Physician: Impairment by Psychiatric Disorders, Including Alcoholism and Drug Dependence. It sounded the alarm on poor mental health in physicians and reported that 100 doctors died by suicide annually — the equivalent of the average medical school graduating class at the time. "If I take my med school class and double it, that's how many physicians die each year," Harrop said. "And here's the bad news, it starts in medical school." Research shows higher rates of depression and suicidal ideation in medical students and residents than in other graduates, with rates varying by stage of training, he noted. In a multischool study, 12% of medical students and residents had probable major depression, 9.2% mild/moderate depression, and suicidal ideation jumped from 6.6% in the first year of medical school to 9.4% in year 4. A recent AANS survey of 346 neurosurgery residents revealed 67% had burnout, and 41% seriously considered quitting. Burnout rose to a high of 76% in the second year and decreased to 49% and 54% in years 3 and 4, respectively. Inadequate operating room exposure, hostile faculty, and stressors outside work were tied to burnout, whereas mentorship was linked to a threefold lower likelihood of burnout. Notably, a 2019 study conservatively estimated that the annual cost of burnout-related physician turnover and reduced clinical hours was $4.6 billion nationally and $7600 per employed physician for an organization. "We need to be kinder to each other, to look out for each other, and to talk to each other," Harrop told conference attendees. 'Death by a 1000 Cuts' A host of factors are associated with physician suicide including long work hours, delayed gratification, difficulty balancing work and home life, changing healthcare systems, lawsuits, and the unique ability to prescribe medications, said Harrop. "In my life, I think of it as death by 1000 cuts. Every day I come in, you've got another person attacking you," he said, referencing 'Death by 1000 Cuts': Medscape National Physician Burnout & Suicide Report 2021. Harrop told Medscape Medical News that talking with numerous experts in this field has made him appreciate that anyone is at a risk for suicide. "The problem is an overload of external resources crushing your existence to the point that you become paralyzed and make the irrational thought that the best solution is to end your life," he said. Ann Stroink, MD, immediate past president of the AANS, said in an interview that one potential trigger for burnout is the current shortage of neurosurgeons in the United States, which has led to increased workloads and potential sleep deprivation among existing neurosurgeons. "To address this critical issue, we've been advocating through legislative channels for additional Medicare[-funded] slots" to train more neurosurgeons, she said. "It's imperative that we take proactive steps to ensure that our healthcare system can sustainably meet the needs of patients, while also supporting the well-being of our neurosurgical professionals." The AANS is also advocating for decreased regulatory burdens associated with Medicare and insurance coverage, such as prior authorization, to help alleviate the administrative burdens that often contribute to burnout among its members, Stroink said. A Model for Suicide Prevention Harrop emphasized that suicide is preventable and that there is "some good news." Turning to another high-risk profession, he noted that the US Air Force was able to reduce its suicide rate by 42.7% between 1994 and 1998 by doing three basic things. The agency established a central surveillance database, restructured prevention services, and, more importantly, began conducting annual suicide prevention and awareness training, using gatekeepers to channel at-risk personnel to appropriate agencies and performing mental health questionnaires at enrollment and annually. Similarly, education, screening, and access to mental health treatment are core recommendations for a national response to depression and suicide in physician trainees, said Harrop, who noted that his own hospital has started using the Patient Health Questionnaire 9-item for its staff. Asked by Medscape Medical News how much progress has been made since The Sick Physician report, Harrop said, "we are probably doing worse" in terms of the number of physician suicides, but "on a positive note, we are better with resources and acknowledgement that a problem exists." He noted that the AANS, which has published a physician burnout series on its Neurosurgery Blog, has shown great interest in this topic and is working to spread the word to help neurosurgeons. "My simple talk has led to me being approached by numerous people and healthcare organizations on how to further focus resources and prevention of this problem." Asked the one thing he would tell his friend, Michael Weinstein, a fellow surgeon, or trainee who's struggling, Harrop said, "I am here for you, and we will get over these temporary problems, which are not significant in the big picture of what you mean to the world." Harrop reported serving as an advisor for Ethicon and Spiderwort. Patrice Wendling is a medical journalist based in Chicago. Note: This article originally appeared on Medscape

Preliminary 6-month results from the first-in-human trial of deep brain stimulation (DBS) of the subgenual singulate cortex (SCC) for chronic low back pain, suggested that the procedure reduces pain, opioid use, and disability. In addition, the procedure was well tolerated with no serious adverse events or complications. "We believe DBS is an option for those patients with severe low back pain who have tried and exhausted medications, physical therapy, and a trial of spinal cord stimulation," principal investigator Ausaf A. Bari, MD, PhD, University of California, Los Angeles, told Medscape Medical News. The findings from the first treated patient were presented on May 4, 2024, at the American Association of Neurological Surgeons 2024 Annual Meeting. A New Treatment Target? "There's a growing amount of scientific evidence including neuroimaging that pain, in general, and chronic low back pain, in particular, affects brain circuits," Bari noted. Therapies such as spinal cord stimulation (SCS) don't address these brain changes, he added, which could explain why SCS seems ineffective for low back pain. "Our hypothesis is that DBS will help these patients by modulating brain circuits that mediate chronic pain," Bari said. These brain circuits have known connections to the SCC, so the researchers propose it may serve as a target for DBS to control chronic low back pain. The patient was a 50-year-old male with a history of medically refractory chronic low back pain for > 20 years and failed back surgery syndrome, who had failed a trial spinal cord stimulation and was taking 10 mg oxycodone three times a day. He underwent stereotactic implantation of bilateral SCC DBS electrodes and placement of an implantable pulse generator. Probabilistic tractography was used to target the SCC region with connectivity to a combination of participant-specific white matter fibers associated with affective neural networks. Stimulation-related side effects were ruled out using awake intraoperative testing. At a 6-month follow up, the patient's pain levels had decreased significantly from baseline, including a 75% drop on the Visual Analog Scale and an 86% drop on the Pain Anxiety Symptom Scale. In addition, there was a 90% decrease in the Oswestry Disability Index score. Weekly opioid doses and oral morphine equivalents were also reduced by 95%, Bari reported. Bari said the trial defined nonsurgical pain as low back pain that does not have a surgically addressable cause and has been deemed to be nonoperative by two surgeons. Investigators plan to enroll a total of 15 patients in the phase 1 study. "We need more clinical trials of DBS that can test the most promising brain areas," said Bari. "This will require multisite clinical trials and cooperation between multiple centers and disciplines." Generalizability Challenging? Commenting on the research for Medscape Medical News, Michael Staudt, MD, MSc, University Hospitals Cleveland Medical Center, Ohio, who was not involved in the study, said one of the challenges is that the definition of nonsurgical back pain can vary widely between surgeons, payers, and interventionalists. "So, when we say nonsurgical back pain, we're already putting [patients] into a category that's a little bit muddy," Staudt said. He also noted that recent, large trials cleared by the US Food and Drug Administration are using spinal cord stimulation for nonsurgical back pain because it is low impact and offers another nonsurgical option for people who fail medical management. "The step between spinal stimulation and deep brain stimulation is a big step," Staudt said. "It's not brain surgery to do a spinal cord stimulator. You won't find many people who are putting in deep brain stimulators, and the challenge with that is it's hard to say if you'd get enough patients in a large enough trial to show overall benefits and cost effectiveness." "I do find it very interesting," Staudt added. "He's [Bari] published it and worked on it for a long time, but the applicability, the generalizability is challenging." The study was funded by the National Institutes of Health. Bari reported serving as a consultant for Medtronic and Novartis and on the scientific advisory boards of Nervonik and Vonova. Co-investigator Nader Pouratian, MD, PhD, reported consulting for Abbott Laboratories and Sensoria Therapeutics. Staudt reported serving as a consultant for Abbott and a scientific advisor and consultant for Boston Scientific. Patrice Wendling is a medical journalist based in Chicago. Note: This article originally appeared on Medscape

Although mental health disorders such as anxiety and depression are common, affecting more than 20% of US adults, many people experience significant delays (sometimes years) in seeking and receiving diagnosis and treatment.Screening for mental health disorders can help promote early detection and treatment, thus improving patients’ quality of life and reducing health care costs. The United States Preventive Services Task Force recommends that all adults be screened for depression and alcohol and drug abuse. To be most effective, tools to assess a patient’s mental health should be validated, brief, reliable, and easy administer. This article reviews some tools that clinicians to screen their patients for depression, anxiety, and substance/alcohol use disorders. Many of these tools are in the public domain and freely available for clinicians to incorporate in their practice. SCID-5 for Assessing Major Mental Disorders The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) provides the diagnostic criteria psychiatric clinicians use when assessing patients for a mental disorder. The Structured Clinical Interview for DSM-5, Clinician Version (SCID-5-CV) provides a semi-structured interview guide to assist in making the major DSM-5 diagnoses. This tool helps ensure that the major DSM-5 diagnoses are systematically evaluated. It is designed to be used by clinicians who are familiar with the DSM-5. A separate version of the SCID-5 is available for evaluating patients who may have a personality disorder. The SCID-5-CV is available for purchase here. Depression Rating Scales Patient Health Questionnaire-9 The Patient Health Questionnaire (PHQ) is a self-administered, criteria-based screening tool for depression and other common mental disorders.Several screening tools have been derived from the PHQ. The most common used is the 9-item PHQ-9, which represents the depression module from the full PHQ. The PHQ-9 takes 1 to 5 minutes to complete, and approximately the same amount of time for a clinician to review the responses. The PHQ-9 asks patients to rate how often during the past 2 weeks they have experienced each of 9 depressive symptoms, from 0 (not at all) to 3 (nearly every day), with a total score ranging from 0 to 27. Scores of 5, 10, 15 and 20 correlate with the lower limits of mild, moderate, moderately severe, and severe depression, respectively. Individuals with major depressive disorder (MDD) seldom score 10 or lower, while a score of 15 or higher usually signifies MDD. The PHQ-9 is available here. Beck Depression Inventory The Beck Depression Inventory (BDI) is a 21-question self-report inventory that asks about characteristic attitudes and symptoms of depression. The BDI takes approximately 10 minutes to complete, and patients need to have at least a fifth-grade reading level to be able to understand the questions in this tool. Each of the 21 questions contains a group of statements about symptom severity that are scored from 0 to 3, with a possible total score ranging from 0 to 63. A score of 29 or higher signifies severe depression. The BDI is available for purchase here. Hamilton Depression Rating Scale The Hamilton Depression Rating Scale (HDRS; also sometimes referred to as HAM-D) is an older, widely used 17-item tool designed for clinicians to use in an unstructured interview.The HDRS was originally developed in 1960 for use with inpatients. It takes approximately 15 minutes to complete. This rating scale does not evaluate atypical symptoms of depression, such as hypersomnia or hyperphagia. Patients with a score of 20 or higher are considered to have at least moderately severe depression. The HDRS is available here. Montgomery-Åsberg Depression Rating Scale The Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-question, clinician-rated tool designed to assess depression severity in adults age 18 and older. Each question is rated on a 7-point scale from 0 (minimal or no symptoms) to 6 (severe symptoms). The MADRS can be completed in 20 to 30 minutes. It is often used to monitor changes in depressive symptoms during treatment. The MADRS is available here. Anxiety Disorders Generalized Anxiety Disorder 7-item The 7-item Generalized Anxiety Disorder scale (GAD-7) is a self-administered tool that can be used to screen for and assess the severity of GAD. The GAD-7 asks patients about the presence of symptoms of anxiety over the past 2 weeks. It is scored from 0 to 21. Scores of 0 to 4, 5 to 9, 10 to 14, and 15 and higher correspond with minimal, mild, moderate, and severe anxiety, respectively. Most patients diagnosed with GAD have a score of 10 or higher. The GAD-7 is available here. Hamilton Anxiety Rating Scale The Hamilton Anxiety Rating Scale (HAM-A) is an older, 14-item, clinician-administered tool for assessing the severity of anxiety symptoms.14,15 The questions on the HAM-A are designed to detect both psychological and somatic symptoms of anxiety. The HAM-A takes 12 to 15 minutes to administer. Each question is scored from 0 (not present) to 4 (severe), with a total possible score of 56. A score of 25 or higher correlates with moderate to severe anxiety. The HAM-A is available here. Alcohol and Substance Use Disorders CAGE Questions Adapted to Include Drugs (CAGE-AID) CAGE is a brief tool originally designed to screen for alcohol abuse and dependence in adults.16, 17 Its name is a mnemonic based on the 4 questions it asks. The CAGE Adapted to Include Drugs (CAGE-AID) modified the original CAGE to include language about drug use as follows16,17: Have you ever felt you ought to Cut down on your drinking or drug use? Have people Annoyed you by criticizing your drinking or drug use? Have you ever felt bad or Guilty about your drinking or drug use? Have you ever had a drink or used drugs first thing in the morning (Eye-opener) to steady your nerves or to get rid of a hangover? Each question is scored 0 (no) or 1 (yes). A score of 2 or more should prompt a full assessment for an alcohol or substance abuse disorder. The CAGE-AID is available here. Alcohol Use Disorders Identification Test The Alcohol Use Disorders Identification Test (AUDIT) is widely used instrument for screening for alcohol abuse.19 It is a 10-question test that can be administered by health care professionals or self-administered by patients. The responses to questions 1 through 8 are scored 0, 1, 2, 3, or 4, while questions 9 and 10 are scored 0, 2, or 4. The possible total score ranges from 0 to 40, with scores of 8 to 14 suggesting hazardous or harmful alcohol consumption and scores of 15 or higher indicating likely alcohol dependence (moderate-severe alcohol use disorder). An interactive version of the AUDIT is available here. Note: This article originally appeared on Psychiatry Advisor

Most people experiencing homelessness have mental health disorders, according to a systematic review and meta-analysis. In an examination of studies that included nearly 50,000 participants, the current prevalence of mental health disorders among people experiencing homelessness was 67% and the lifetime prevalence was 77%. "The relationship is likely bidirectional, where experiencing homelessness may exacerbate mental health symptoms or where having a mental health disorder may increase an individual's risk for experiencing homelessness," lead author Rebecca Barry, PhD, a postdoctoral fellow at the University of Calgary in Calgary, Alberta, Canada, told Medscape Medical News. "There are also likely stressors that increase both risk for homelessness and risk for developing mental health disorders. This study examines prevalence but does not examine causal relationships," she said. The findings were published on April 17, 2024, in JAMA Psychiatry. A Growing Problem To determine the current and lifetime prevalence of mental health disorders among the homeless population, the researchers analyzed 85 studies that examined this question in participants aged ≥ 18 years. The review included 48,414 participants, including 11,154 (23%) women and 37,260 (77%) men. The lifetime prevalence of mental health disorders was significantly higher in men experiencing homelessness (86%) than in women (69%). The most common mental health disorder was substance use disorder (44%), followed by antisocial personality disorder (26%), major depression (19%), bipolar disorder (8%), and schizophrenia (7%). The prevalence of current and lifetime mental health disorders among the homeless population was higher than that that observed in the general population (13%-15% and 12%-47%, respectively). The results resembled those of a previous review that estimated that 76% of people experiencing homelessness living in high-income countries have mental health disorders. "Even though our results are not surprising, they still are drawing attention to this issue because it is a big problem in Canada, the United States, Europe, and other places," senior author Dallas Seitz, MD, PhD, professor of psychiatry at the University of Calgary's Cumming School of Medicine, told Medscape Medical News. "The problem is concerning, and it's not getting better. Addiction and mental health problems are becoming more common among people who are homeless." The bottom line is that people need affordable housing and mental health support, said Seitz. "It's a housing problem and a health problem, and we need adequate resources to find better ways for those two systems to collaborate. There are public safety concerns, and we have to try and bring services to people experiencing homelessness. You have to come and meet people where they're at. You have to try and establish a trusting relationship so that we can get people on the path to recovery." 'It's Really About Income' Commenting on the findings for Medscape Medical News, Stephen Hwang, MD, professor of medicine at the University of Toronto, Toronto, Ontario, Canada, said, "There have been previous studies of this type, but it is good to have an updated one." Hwang, who is also chair in Homelessness, Housing, and Health at St. Michael's Hospital, did not participate in the research. The findings must be understood in the proper context, he added. For one thing, grouping together all mental health disorders and giving a single prevalence figure can be misleading. "They are including in that category a diverse group of conditions. Substance use disorder, personality disorder, schizophrenia, and depression are all lumped together. The 67% prevalence seems very high, but it is a combination of many different conditions. I just don't want people to look at that number and think that this means that everyone is a substance user or everyone has schizophrenia," said Hwang. Also, some readers might interpret the findings to mean that mental problems are the reason people are homeless, he added. "That would be an incorrect interpretation because what this study is showing is that people with mental health disorders have a higher risk for becoming homeless. It doesn't mean that it caused their homelessness. What really causes homelessness is a lack of affordable housing," said Hwang. "In a city or community where housing is very expensive, there's not enough for everyone to be housed, there is a lot of competition for housing, and there's not enough affordable housing for a number of reasons, we know that people with mental health conditions and substance use disorders will be among the first to lose their housing," he said. "It's really about income. There are many reasons why a person cannot afford housing. So, not being able to earn enough money to afford it because you have a mental health disorder or substance use disorder is a common underlying reason for homelessness." Hwang also pointed out that people with mental illness who can access support, either through family members or through mental health care, and who also have the income to afford such services do not become homeless. "Schizophrenia is seen in every population of the world at a rate of 1%. But you travel to certain cities and you see people who appear to have schizophrenia wandering the streets, and you go to other cities in the world and you don't see anyone who looks like they're homeless and have schizophrenia," he said. "It's not because there are fewer people with schizophrenia in those cities or countries; it's because people with schizophrenia are treated differently. The rate of homelessness is determined not by how many people have that condition [eg, schizophrenia] but by how we treat those people and how we set up our society to either support or not support people who have disabilities." The study was funded by the Precision Care With Information, Science and Experience - Mental Health grant funded by the Calgary Health Foundation. Barry is supported by the Harley Hotchkiss Samuel Weiss Postdoctoral Fellowship awarded by the Hotchkiss Brain Institute at the University of Calgary. Barry reported having no relevant financial relationships. Seitz reported grants from Calgary Health Foundation during the conduct of the study as well as grants from University Health Foundation, the Canadian Institutes of Health Research, the Public Health Agency of Canada, the Alzheimer's Association, and the Hotchkiss Brain Institute. He received honoraria for guideline development from the Canadian Coalition for Seniors Mental Health outside the submitted work. Hwang reported no relevant financial relationships. Note: This article originally appeared on Medscape

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

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

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