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Keypoint: Why a blue dye may be a viable treatment for psychiatric disorders. Methylene blue is both a dye and a medicine. Methylene blue has been demonstrated to improve depression, as well as anxiety and Alzheimer's disease. Methylene blue also enhances memory. Methylene blue is both a dye and an FDA-approved medication. Described as the first fully synthetic drug used in medicine, methylene blue was initially synthesized by a German chemist in 1876, and 15 years later, it was employed as a treatment for malaria. This dye/medicine continued to play an important role as an antimalarial medication during the First and Second World Wars. In the late 19th century, methylene blue was explored as a treatment for schizophrenia, and later, it was employed as a treatment for urinary tract infections, an antidote for carbon monoxide and cyanide poisoning, and a drug for septic shock. Today, this amazing medicant is being explored as a treatment for neuropsychiatric conditions. The chemical structure of methylene blue is similar to that of both tricyclic antidepressants and the anti-seizure medicine carbamazepine. However it’s mechanisms of action are quite different from these medications. Some of these mechanisms are dose dependent, meaning that higher doses can have the opposite effects of lower doses. The specific mechanisms of methylene blue include antibacterial, antiviral, and anti-inflammatory effects; blockade of GABA-A receptors; inhibition of monoamine oxidase A (MAO-A); improvement in mitochondrial functioning; and inhibition of tau protein aggregation. Methylene blue also affects the transmission of the primary excitatory neurotransmitter in the human brain, glutamate, by inhibiting N-methyl-D-aspartate (NMDA) receptors. This results in an increase in brain-derived neurotrophic factor (BDNF). In this way, methylene blue functions similarly to ketamine and other psychoplastogens such as psilocybin and LSD, but it does not cause alterations in consciousness, such as those produced by psychedelic medicines. Antidepressant effects Since the 1970’s, methylene blue has been found to be an effective antidepressant medicine in multiple studies. For example, a 1986 study performed by researchers in Scotland explored the effects of 15 mg of methylene blue administered daily to 13 women who suffered from severe depression. Their response was compared to 15 women who were given a placebo. The women who received a placebo did not improve, but those who were given methylene blue showed marked improvement. In fact, within one week, the women who were receiving methylene blue showed a statistically significant improvement in their depressive symptoms relative to those in the placebo group. In another study, 24 chronically and/or severely depressed participants were treated with methylene blue 200 mg or 300 mg daily. Nineteen of these individuals were diagnosed with bipolar disorder, and 14 of these showed “definite improvement.” In 1986, a two-year randomized, cross-over study examined the effects of 300 mg versus 15 mg of methylene blue daily in 17 individuals with bipolar disorder . All participants also took lithium throughout the study. The investigators found that individuals who took the higher dose were significantly less depressed than those who took the lower dose, and no change in manic symptoms occurred in either group. Hospitalization rates were reduced following treatment with either dose. Another study involved a double-blind crossover design with men or women who were diagnosed with bipolar I or bipolar II disorder and were partially stabilized on lamotrigine. Participants were randomly assigned to receive either methylene blue at a dose of 15 mg or 195 mg daily for three months, then they were switched to the other dose. They continued to take lamotrigine throughout the study. Twenty-seven individuals completed the study. Methylene blue was well tolerated, and no severe side effects were reported. None of the individuals experienced a worsening of manic symptoms. However, there was an overall reduction in symptoms of depression and anxiety . Methylene blue as a treatment for other psychiatric disorders In 1938, a study described the use of methylene blue as a treatment for schizophrenia. More than 50 years later, another study explored the use of methylene blue in eight patients with schizophrenia who failed to respond to conventional antipsychotic medications. These individuals demonstrated statistically significant improvement following treatment with methylene blue, and their symptoms worsened when the medicine was discontinued. A double-blind, randomized, placebo-controlled Phase II trial involving 321 individuals with mild or moderately severe Alzheimer’s disease found moderate improvement following the administration of 138 mg of methylene blue daily after 24 weeks, but higher (228 mg) and lower (69 mg) doses were ineffective. Methylene blue has also been found to enhance memory and exert neuroprotective effects. Side effects with this medicine, which are typically mild and well tolerated, may include blue-colored urine, nausea, and headache. Summary While newer antidepressant medications often cost hundreds of dollars per month, older therapeutics that can no longer be patented may provide effective and more affordable options for people suffering from psychiatric illnesses who cannot afford more expensive treatments. Methylene blue is one such medicine. Further studies will help us understand more about the potential benefits of this unique therapeutic, as well as its benefits for the treatment of psychiatric and neurodegenerative disorders. Note: This article originally appeared on Psychology Today .

Keypoint: Recent updates in suicide prevention interventions for older adults and how a novel tablet application may provide relief to individuals at high risk of suicide. Suicide in late life constitutes a major public health concern. In 2019, the Centers for Disease Control and Prevention (CDC) reported that the suicide rate for all ages in the United States was 14.5/100,000. Middle-aged and older adults have higher rates of suicide than their younger counterparts (19.41/100,000 for individuals aged 55 to 64), and the highest rate of suicide remains for older males (39.9/100,000 for males aged 75 and older).1 Despite the alarmingly high rates, psychosocial interventions for this population are understudied and urgently needed. Mobile devices provide a unique and powerful opportunity to deliver interventions to suicidal individuals during periods of increased suicide risk.2 With the current COVID-19 pandemic , reliance on digital health technology is growing, and developing targeted interventions that can be used remotely by older adults during times of emotional crisis is of paramount importance. Characteristics and Risk Factors To establish effective psychosocial interventions, risk factors for late-life suicide must be examined. Sociodemographic and clinical factors that are more commonly found in middle-aged and older individuals (eg, widowhood, cognitive decline, etc) play an important role in suicide risk . Understanding the complex interaction of these late-life occurrences can guide efforts in designing preventative interventions. Demographic Factors According to the CDC, middle-aged and older adults account for the highest number of suicides compared to younger populations. In 2018, adults aged 65 and older were reported to make up 16% of the US population, but were responsible for 18.8% of suicides. While there are an estimated 25 suicide attempts for every completed suicide in the general population, approximately 1 in 4 suicide attempts results in death for older adults. Gender, race, and ethnicity also influence suicide risk and behavior. Women consistently account for a higher number of suicide attempts than men. There are 3 female attempts for each male attempt, yet an estimated 3.6 males die by suicide for every 1 female death. This discrepancy is attributed to the difference in method, because men often use more lethal methods when attempting suicide. In comparison to other racial and ethnic groups, non-Hispanic American Indian/Alaska Native and non-Hispanic white people account for the highest rates of suicide at 22.3 and 17.6/100,000, respectively. Cognitive Functioning and Physical Illness As many as 1 in 9 older adults suffer from some form of cognitive impairment. Cognitive impairment is often responsible for reducing decision-making capacity and affecting emotion regulation abilities, potentially contributing to suicidal ideation and behavior. Discrepancies in literature regarding suicide risk and cognitive impairment suggest that dementia can either be a risk factor or a protective factor depending on the progression and severity of symptoms. However, a review on suicide risk and Alzheimer disease found that Alzheimer disease is associated with a moderate suicide risk in older adults, even several years after diagnosis. Physical illness and functional disability in late life are also strongly associated with suicide. In a cohort study by Erlangsen and colleagues,12 investigators found that certain cancers and liver disease, specifically, are most closely associated with suicidal outcomes. Despite strong associations found in research, reviewers of the literature advise caution when using physical illness to determine risk, many noting that identifying physical illness does not serve as a predictor for suicide, nor does quantifying the severity of symptoms. Psychiatric Illness and Suicidal Behavior Psychiatric illness is noted in up to 97% of late-life suicides, with major depression cited as the most strongly associated psychiatric disorder. Retrospective analysis of psychiatric illness and suicide mortalities in older adults in Denmark highlight recurrent depression as contributing to the highest rate of suicides in adults aged 60 and older, followed closely by other affective disorders and reaction to stress/adjustment disorders. This risk was significantly increased for individuals who were hospitalized for any type of psychiatric disorder, with hospitalized psychiatric illness accounting for 22.3% of male suicides aged 60 and older. One of the predictors of suicidal behavior is suicidal ideation, especially active suicidal ideation with intent or plan. However, in older adults who are seeking aging services, even passive suicidal ideation is an indicator of suicide risk. Despite the elevated number of late-life suicides, suicidal older adults often go undetected due to lower rates of reporting, especially in primary care where older adults most likely seek medical treatment. This information highlights the need for increased identification strategies, as well as enhanced efforts to prevent the onset of suicidal ideation given the high mortality rate in late-life suicide attempters. Psychosocial Factors Interpersonal losses including widowhood or death of friends and family are commonplace in advancement of age. The accompanying stress, sense of loneliness, and social disconnection in response to loss is associated with elevated suicide risk, especially within the first year after the death of a close relative. Passive and active suicidal thoughts are particularly common among older adults in long-term care facilities, and social isolation and loneliness are some of the most frequently reported bases for suicidal thoughts. The relationship between perceived social support and psychiatric illness, most notably depression, is strong even when controlling for other factors, such as negative affectivity and overreporting of experiences. This points toward a need for more dynamic psychosocial interventions. Existing Psychosocial Interventions for Suicide Prevention Current randomized, controlled trials (RCTs) that evaluate psychosocial interventions for older adults are typically developed to address depression or other affective disorders in young adults and are not specifically targeted toward suicidality. Of the few published RCTs that measure suicidal ideation as a primary outcome in older adults, the intervention and assessment methods are diverse. Conwell investigated the effect of a peer companionship program on socially disconnected older adults, but saw no significant difference in suicidal ideation outcomes between the treatment and control groups. Two studies, conducted by Ecker and Kumpula, evaluated adaptations of CBT on veterans with suicidal ideation. The first study was a 4-month brief cognitive behavioral therapy (CBT), and the second was CBT for depression compared against 2 other evidence-based psychotherapies. Both authors reported a reduction in suicidal ideation in the CBT/bCBT groups compared to control groups. Gustavson and Lutz examined suicidal ideation as a primary outcome in tests of problem-solving therapy in older adult populations. These studies both saw significant reductions in suicidal ideation in the treatment groups; however, 1 study tailored the intervention toward older adults with depression and executive dysfunction, and the other targeted subjects with functional disability, making the interventions difficult to compare. Kiosses investigated the effects of problem adaptation therapy (PATH) on suicidal ideation, an intervention that utilizes emotion-regulation techniques and compensatory strategies in older adults with depression and cognitive impairment. The authors saw a reduction in suicidality in the PATH participants, but the reduction was not significantly different from the supportive therapy control group. The samples in the aforementioned studies represent specific populations (ie, veterans with medical illness, older adults with functional disabilities), and are not representative of the general older adult population. The heterogeneity of the interventions creates difficulty in both between-study comparisons and generalizability to the general population. Moreover, these studies often exclude those who express active suicidal ideation, leaving out those who are at greater risk of suicide. The results are promising; however, it is important that findings be replicated with larger and more representative samples to more accurately examine the effectiveness and promote generalizability of the interventions. Role of Technology in Treatment The onset of the COVID-19 pandemic and the associated policies have the potential to exacerbate the severity of the previously identified risk factors for suicide in older adults. Social-distancing guidelines, stress, and limited access to health care may contribute to increased feelings of isolation and loneliness, worsening of cognitive and functional abilities, and intensification of symptoms of psychiatric disorders. Technology offers the opportunity to alleviate logistical barriers to receiving clinical interventions for older adults who may have difficulty adhering to treatment. As the reliance on telehealth increases, more thorough investigation into remote psychosocial intervention methods targeted specifically for this population is particularly essential. Literature on the role of technology treatment for suicide prevention in older adults is sparse. Preliminary findings available on feasibility and acceptability of technology-based mobile interventions suggest promising effects of improvement, but further testing is needed. In a review of mobile health technology for suicide prevention, one intervention, Virtual Hope Box (VHB), was tested in middle-aged adults. The study recruited both young and middle-aged veterans with a mean age of 46 years old and tested an augmentation of CBT using smartphone capabilities to enhance and personalize the experience with a “hope box.” The study evaluated the effect of the application on intensity of suicidal ideation and importance of reasons for living, but the results yielded no statistically significant treatment effect on these outcomes between the treatment and control groups. Our research at the Emotion, Cognition, and Psychotherapy Lab at Weill Cornell Medicine aims to reduce suicide risk by employing a simplified, personalized, and easy-to-use mobile intervention. WellPATH is a tablet application that focuses on emotion regulation strategies (specifically, cognitive reappraisal strategies, which focus on seeing a situation from a different perspective) to reduce negative emotions associated with increased suicide risk. It is a personalized, mainly standalone, mobile intervention that incorporates patient-specific techniques that can be accessed when the patient is faced with negative emotions. The patient and WellPATH interventionist identify situations, problems, or concerns that trigger intense negative emotions that may lead to increased suicidal ideation or behavior and develop personalized cognitive reappraisal strategies to reduce the intense negative emotions. Preliminary results indicate that patients are able to utilize the user-friendly interface with ease and are highly satisfied with the support provided by WellPATH. The WellPATH application takes into consideration characteristics unique to older adults and offers immediate access to an intervention that is easy to use. It addresses the need for a mobile suicide prevention intervention for middle-aged and older adults at high suicide risk, which is particularly germane, given the increased reliance on telehealth . Concluding Thoughts The topic of suicide in older adults requires greater consideration. Identification of risk factors is valuable in understanding elder suicidality; however, further attention is encouraged for the development and evaluation of effective interventions tailored to older adults. The few psychosocial interventions mentioned show overall promising results, but unfortunately, there is little available data beyond what has been described. The novel WellPATH tablet application has the opportunity to provide relief to individuals at high risk of suicide by offering an immediate intervention to patients in their actual environment. With the rapid increase in population of middle-aged and older adults, the continued exploration of adaptive preventative interventions is essential for safeguarding the well-being of this increasingly vulnerable population. Note: This article originally appeared on Psychiatric Times .

How common are psychiatric disorders in unhoused individuals? Key points: Psychiatric illnesses are common in unhoused individuals, and the prevalence appears to be increasing. Substance use disorders, including alcohol use disorder, occur in over 40% of the unhoused population. About 14% of unhoused persons have a psychotic disorder. Interventional approaches should address both housing and mental health care. Homelessness can predispose individuals to psychiatric disorders. Conversely, certain psychiatric disorders can increase the risk of becoming homeless. A recent article in JAMA Psychiatry by Rebecca Barry, Dallas Seitz, and colleagues provides important information about the prevalence of specific psychiatric disorders in persons who are experiencing homelessness. These authors performed a meta-analysis of data reported in 85 research articles. They selected these articles because they fulfilled rigorous quality criteria and included diagnoses based on the International Classification of Disease (ICD), the Diagnostic and Statistical Manual of Mental Disorders (DSM), or standardized diagnostic instruments. They excluded studies on suicide, self-harm, cognitive impairment (except dementia), neurological disorders, and smoking. They also excluded studies where the entire population was likely to have a psychiatric diagnosis; for example, studies focusing on patients in psychiatric clinics. Most studies defined “homeless” as living in shelters or in places not intended as a permanent dwelling. The final analysis examined data from 48,414 unhoused adults (18 years and older). Current psychiatric disorders Overall, the investigators found that two-thirds (67%) of unhoused persons were diagnosed with a current psychiatric disorder. The most common was substance use disorder. Alcohol use disorder occurred in over 25% of these individuals, and substance use disorders, including alcohol use disorder, occurred in over 43%. Unhoused individuals experienced psychotic disorders at a markedly increased rate compared to the general population. In some studies, about 14% of those experiencing homelessness were diagnosed with a psychotic disorder. In other studies, about 7% were diagnosed with schizophrenia and 8% with bipolar disorder. Although not specifically reported in this study, many individuals with psychotic disorders also have substance use disorders. Antisocial personality disorder, major depression, anxiety disorders, and post-traumatic stress disorder were also common in unhoused individuals, occurring in about 26%, 19%, 14%, and 10.5%, respectively. The overall lifetime prevalence of psychiatric disorders among individuals experiencing homelessness was estimated to be 75%. It was higher for men (86%) than for women (69%). Important trends The authors report that there are indications that the prevalence of current mental illness in unhoused populations may be increasing. In studies conducted prior to 2010, the prevalence was 48% compared with 76% in studies reported after 2010. Implications The great majority of unhoused individuals have a current psychiatric disorder. Homelessness may exacerbate psychiatric disorders, and certain psychiatric disorders may increase the risk of homelessness. For strategies addressing the mental health needs of unhoused individuals to be most successful, access to both housing and mental health treatment must be considered. In addition, better access to quality mental health care may help prevent some individuals from experiencing homelessness in the first place. Note: This article originally appeared on Psychology Today .

There is a bidirectional, causal relationship between mental illness and poverty, new research showed. "This study indicates that certain mental health problems can make a person's financial situation uncertain. But conversely, we also see that poverty can lead to mental health problems," study investigator Marco Boks, MD, PhD, corresponding author, Amsterdam University Medical Center, Amsterdam, the Netherlands, said in a press release. The findings were published online on July 10, 2024, in Nature Human Behavior . Disentangling Cause and Effect Previous research shows a correlation between poverty and mental illness, but the direction of the association has always been uncertain and complicated by factors such as stress, housing insecurity, and substance use. To investigate a potential causal relationship between poverty and mental illness, investigators used data from more than 500,000 participants in the UK Biobank and the international Psychiatric Genomic Consortium, including 18 genome wide association studies. Investigators developed a measure of poverty based on household income, occupational income, and social deprivation. They then examined the causal relationship of poverty on nine mental illnesses. These included attention-deficit hyperactivity disorder (ADHD) , anorexia nervosa (AN), anxiety disorder, autism spectrum disorder, bipolar disorder, major depressive disorder (MDD), obsessive-compulsive disorder, posttraumatic stress disorder, and schizophrenia. They also extended the analyses to potential confounders such as cognitive ability. Using genomic structural equation modeling, the team found a causal bidirectional relationship between poverty, ADHD, and schizophrenia. They found that lower income was causally related to these disorders and that there was also a causal relationship between the disorders and lower income. They also found a one-directional causal effect of poverty on MDD and an inverse causal relationship between poverty and AN, which was causally associated with higher incomes (all P < .05). "This evidence supports a vicious cycle between poverty and severe mental illness," the authors noted. The effects of poverty on mental illness were reduced by approximately 30% when investigators adjusted for cognitive ability. The investigators noted that the generalizeablity of the findings are limited because most of the genetic studies were conducted in populations of European ancestry from high-income countries. In addition, they noted that psychiatric phenotypes are complex and heterogeneous, which generally translates to low power. "The findings of this study reiterate the need to further unravel the roles of poverty and mental illness and to use this insight to advance mental health for all. The choice of which action to take to address the problem is a political matter, but attention is warranted considering increasing income inequalities worldwide, as well as the increasing incidence of mental illness," the researchers noted. Note: This article originally appeared on Medscape .

Keypoint: NIH-funded study of conduct disorder identifies new brain areas associated with the disorder, offering future directions for research efforts and clinical practice. A neuroimaging study of young people who exhibit a persistent pattern of disruptive, aggressive, and antisocial behavior, known as conduct disorder, has revealed extensive changes in brain structure. The most pronounced difference was a smaller area of the brain’s outer layer, known as the cerebral cortex, which is critical for many aspects of behavior, cognition, and emotion. The study, co-authored by researchers at the National Institutes of Health (NIH), is published in The Lancet Psychiatry. “Conduct disorder has among the highest burden of any mental disorder in youth. However, it remains understudied and undertreated. Understanding brain differences associated with the disorder takes us one step closer to developing more effective approaches to diagnosis and treatment, with the ultimate aim of improving long-term outcomes for children and their families,” said co-author Daniel Pine, M.D., Chief of the Section on Development and Affective Neuroscience in NIH’s National Institute of Mental Health. “Critical next steps are to follow children over time to determine if differences in brain structure seen in this study are a cause of conduct disorder or a long-term consequence of living with the disorder.” A collaborative group of researchers examined standardized MRI data from youth ages 7 to 21 who had participated in 15 studies from around the world. Analyses compared the surface area and thickness of the cerebral cortex and the volume of deeper subcortical brain regions between 1,185 youth diagnosed with conduct disorder and 1,253 youth without the disorder. Additional analyses compared the cortical and subcortical brain measures between boys and girls, age of symptom onset (childhood vs. adolescence), and level of empathy and other prosocial traits (high vs. low). Youth with conduct disorder had lower total surface area across the cortex and in 26 of 34 individual regions, two of which showed significant changes in cortical thickness. Youth with conduct disorder also had lower volume in several subcortical brain regions, including the amygdala, hippocampus, and thalamus, which play a central role in regulating behaviors that are often challenging for people with the disorder. Although some of these brain regions, like the prefrontal cortex and amygdala, had been linked to conduct disorder in previous studies, other regions were implicated in the disorder for the first time. The associations with brain structure did not differ between boys and girls and were seen across conduct disorder subgroups based on age of onset and level of prosocial traits. Youth who exhibited signs of a more severe form of the disorder, indicated by a low level of empathy, guilt, and remorse, showed the greatest number of brain changes. These findings from the largest, most diverse, and most robust study of conduct disorder to date are consistent with a growing body of evidence that the disorder is related to the structure of the brain. The study also provides novel evidence that brain changes are more widespread than previously shown, spanning all four lobes and both cortical and subcortical regions. These findings offer new avenues for investigating potential causal links between differences in brain structure and symptoms of conduct disorder and for targeting brain regions as part of clinical efforts to improve diagnosis and treatment. Note: This article originally appeared on NIMH .

The commercialization of cannabis that followed its legalization for nonmedical use was associated with an increase in hospitalizations for cannabis-related health problems, including cannabis-induced psychosis, according to new research. In a repeated cross-sectional analysis that included some 26.9 million individuals, researchers found that the rate of hospitalizations due to cannabis increased 1.62 times between 2015 and 2021. The rate of hospitalizations increased most precipitously after commercialization, including a 40% increase in hospitalizations for cannabis-induced psychosis. Decline With Legalization Canada has a universal healthcare system, and the researchers accessed health administrative databases that recorded all acute hospitalizations for patients aged 15 to 105 years in the four most populous provinces: Ontario, Quebec, Alberta, and British Columbia. They compared changes in rates of hospitalizations due to cannabis over the following three time periods: prelegalization (January 2015 to September 2018), legalization with product and store restrictions (October 2018 to February 2020), and commercialization (March 2020 to March 2021). There were 105,203 hospitalizations due to cannabis during the study period. Most (65.8%) were in males, and one third were in adolescents and young adults aged 15 to 24 years. The age- and sex-standardized rate of hospitalizations due to cannabis increased 1.62 times: from 3.99 per 100,000 individuals in January 2015 to 6.46 per 100,000 individuals in March 2021. The largest relative increase in hospitalizations was for cannabis-induced psychosis, which rose 40% during the commercialization period, compared with the prelegalization period (rate ratio, 1.40). The period of legalization with restrictions was associated with a gradual monthly decrease of −0.06 in hospitalizations due to cannabis per 100,000 individuals. During the commercialization period, which coincided with the COVID-19 pandemic, there was an immediate increase of 0.83 hospitalizations due to cannabis per 100,000 individuals. 'Legalization, Not Commercialization' Legalizing cannabis removes an important reason for incarceration, said Myran. "That is an important public health gain. There’s very compelling data that making cannabis illegal ended up giving a lot of young people criminal records, and in Canada, it’s disproportionately in Black and indigenous youth. You get a criminal record, and it has major social harms." Before cannabis was legalized in Canada, it became easier to obtain. Gray market stores selling cannabis were no longer being closed by the police. In the lead-up to legalization, cannabis use increased. But once legalization with restrictions was instituted, hospitalizations for cannabis use declined, said Myran. "Legalization in Canada has taken a graduated rollout, so you have an initial legalization with restrictions, where the government would only allow the sale of dried cannabis flower, there were almost no stores, and you actually see these rates decline. But later on, when the market matures and you have a vast amount of stores, new products like vape pens and edibles and concentrates and cannabis-infused beverages, and which happens to overlap with the COVID-19 pandemic, you see a jump in cannabis hospitalizations," he said. Cannabis use can be very harmful for some individuals. It is well known that cannabis use in adolescents and young adults is associated with the development of psychosis, said Myran. "There are individuals who are predisposed to develop psychosis, and cannabis seems to bring on psychotic episodes in those who are vulnerable. In one study, 26% of people who presented to the emergency department with an episode of cannabis-induced psychosis went on to develop schizophrenia within the next 3 years," he said. We need legalization, not commercialization, Myran said. Promoting Cannabis Misuse? Increased commercialization is increasing the availability of cannabis, hence problems with abuse and overuse will occur, he added. Sherry did not participate in the research. "We know from the alcohol literature, the tobacco literature, and increasingly from the cannabis literature that with the increase of the physical availability of cannabis outlets, you also increase potential for abuse of cannabis," he said. While claims that sales of cannabis products provide a source of revenue for governments may be true, the main source of that revenue is the regular user, Sherry said. "The dirty secret in the legalization and commercialization of cannabis is that most of the revenue comes from frequent or addicted customers. Someone who buys 1 gram and uses it recreationally in a month is not a good customer. The good customers are frequent and addicted individuals who are going to smoke 5 grams of cannabis a day." Commercialization results in more direct appeals to addiction-prone people, Sherry added. "For instance, in Nova Scotia, we promote cannabis as a way to relax and enhance your experience. If you are addiction-prone, that messaging, and the increased physical availability of cannabis with commercialization, means that we are going to see more cannabis problems. So, if you add more cannabis outlets, as you heavily commercialize cannabis products, you add more cannabis problems to our society." Cannabis is not a benign substance, Sherry emphasized. Increasing awareness of the associated harms, as has occurred with tobacco, would be a better way of marketing cannabis, he suggested. "Rather than the current relaxed and permissive attitude, we need to switch to one of grudging tolerance, recognizing that cannabis is going to be part of our landscape, that some people are going to use it and some are going to misuse it, and that we need to discourage the consumption of cannabis as a public health problem," said Sherry. The study was supported by a grant from the Canadian Centre on Substance Use and Addiction and fellowships from the Canadian Institutes of Health Research and the University of Ottawa Department of Family Medicine. Myran reported grants from Canadian Institutes of Health Research during the conduct of the study. Sherry reported no relevant financial relationships. Related Topics: One Life Psychiatry

HELSINKI — Nightmares in middle age are linked to a significantly increased risk for subsequent dementia, new research suggested. However, one expert is skeptical that this is the case. Investigators found that middle-aged adults who reported having weekly distressing dreams at baseline had a fourfold increased risk of developing dementia compared with their counterparts who had no nightmares. "It is likely that distressing dreams are either a causal risk factor for dementia or one of the earliest signs of it," said study investigator Abidemi Otaiku, MD, Imperial College London, London, England. The findings were presented here at the Congress of the European Academy of Neurology (EAN) 2024 annual meeting. Robust Link As previously reported by Medscape Medical News , Otaiku and colleagues found healthy middle-aged adults from the MIDUS study who had bad dreams at least once a week were four times more likely to experience cognitive decline over the following decade than those without distressing dreams. In addition, older adults who reported nightmares had a twofold increased risk for all-cause dementia. The current study furthers the previous research by analyzing a subset of study participants who had genetic data available that was based on blood tests, saliva samples, and family history to determine if these had any impact on the previous findings. "We found that after controlling for genetic factors, the association between distressing dreams and both cognitive decline and dementia remained robust," Otaiku told Medscape Medical News. "We also found that there was no significant relationship between distressing dream frequency and genetic factors in either age group." Given that there's no cure for Alzheimer's disease (AD) or other dementia types, "it's important that we identify people at the early stage before they develop symptoms, so they can benefit from disease-modifying drugs, when available, and preventive strategies," Otaiku added. Future studies are needed to determine whether treating distressing dreams could help slow cognitive decline and/or prevent dementia, he said. In response to a question from the audience about rapid eye movement (REM) sleep behavior disorder following his talk, Otaiku said he did not have data on this but added that he believes it's unlikely that it explains the association between bad dreams and dementia. He pointed out that REM sleep behavior disorder is very rare, affecting < 0.05% of the population of those aged 50 years and older. Second, he said there has been one study, to his knowledge, looking at REM sleep behavior disorder and all-cause dementia, which showed the disorder did not predict all-cause dementia, whereas nightmares were predictive. Finally, said Otaiku, there are data on diagnosed sleep disorders from one of his studies, which showed that even when all participants with a diagnosed sleep disorder were excluded, the relationship between nightmares and dementia risk remained robust. "Therefore, it seems unlikely that REM sleep behavior disorder explained the association," he said. Otaiku noted his team also adjusted for neuropsychiatric disorders such as anxiety, depression, and stress, and still the link between nightmares and dementia risk remained robust. Similarly, they adjusted for medication use, including antidepressants, benzodiazepines, and hypnotics, and found this also didn't explain the increased dementia risk. He noted that the study had an outcome of all-cause dementia and that his team didn't have access to data on specific dementia diagnoses. "Presumably, Lewy body dementia would be one of the strongest associations, but given that this makes up less than 5% of diagnoses in the community, it's likely that the effects may apply to Alzheimer's disease too, and previous studies have shown that nightmares are more common in Alzheimer's disease at certain stages," he concluded. A More Likely Culprit? Commenting on the research for Medscape Medical News , Sebastiaan Engelborghs, MD, PhD, professor and chair of neurology, Vrije Universiteit Brussel, Brussels, Belgium, and co-chair of the EAN Scientific Panel on Dementia and Cognitive Disorders, said the findings are not novel. "I suspect the subjects with 'distressing dreams' to have rapid eye movement (REM) sleep behavior disorder. This can only be ruled out by a sleep exam, which was not performed — to my knowledge — in this study." "It is well-known that REM sleep behavior disorder may precede dementia by many years. One of the key symptoms of REM sleep behavior disorder are nightmares, or 'distressing dreams'…and this is why we always ask about sleep and nightmares during consultations in the memory clinic," Engelborghs added. "That is also why we follow up on cognitively healthy subjects who show up with nightmares, suggestive of REM sleep behavior disorder, as we do know that they are at increased risk of developing dementia, and we disclose this to them," he added. Speaking to Otaiku's suggestion that future trials could assess whether treating distressing dreams might slow the onset of, or prevent, dementia, Engelborghs said that his patients with REM sleep behavior disorder are treated with specific medications "as the symptoms can be very distressing." However, he noted treating sleep symptoms does not reduce dementia risk. Disordered sleep is often the first, early manifestation of neurodegeneration that is the cause of future dementia, he said. Note: This article originally appeared on Medscape .

Keypoint: Research shows an increased risk for suicidal thoughts, suicide attempts, and even death by suicide following brain injury. europsychiatric disorders regularly occur following brain injury and are often diagnosed within a year of the injury. Mood disorders, particularly major depressive disorder (MDD), are the most frequently diagnosed DSM-5 psychiatric disorders after brain injury. Mood disorders can develop with or without a preinjury history of psychiatric disorder, and can increase risk for suicidal thoughts. MDD Following Brain Injury Prospective studies using structured clinical interviews report rates of depression between 13.9% and 23.2% within the first year of injury for mild brain injury. Reported rates of MDD for a wider range of injury severity are higher, ranging from 15.3% to 33%. Risk factors for MDD include preinjury depression, focal lateral lesions and left anterior lesions, and psychosocial stressors including social isolation and maladaptive coping. MDD following brain injury was associated with comorbid anxiety and self-reported lower quality of life at 1 year after the injury. Suicide Risk and Suicidality Studies report an increased risk for suicidal thoughts, suicide attempts, and even death by suicide following brain injury. Makelprang followed a cohort of adults with traumatic brain injury (TBI) for 1 year after discharge from the hospital, and found that 25% of the sample reported suicidal ideation within the first year of injury. The strongest predictors of suicidal ideation after brain injury included prior history of suicide attempt, neuropsychiatric diagnosis (depression, bipolar disorder), and less than a high school education. Simpson and Tate reported a lifetime prevalence rate of 26.2% for suicide attempt in an outpatient sample with TBI. They also examined the clinical features of suicide attempts after TBI in an outpatient cohort followed over a 24-month period. Their data set included 43 patients who made a total of 80 suicide attempts; 30% of the attempts were preinjury and 70% postinjury. Over 55% of the sample made a single attempt, 25.6% made 2 attempts, and 18.6% made 3 or more attempts. Of those that made 3 or more attempts, the repeat attempts occurred within 13 months of the index attempt, and over one third making multiple attempts used the same method. Excessive alcohol intake within the prior 24 hours, psychological distress brought on by antecedent stressors (arguments, loss of a significant relationship, negative feedback, etc), and hopelessness combined with high suicidal ideation, were associated with suicide attempt after TBI. Treatment and Prevention Prevention and treatment interventions for suicidal ideation and attempt can include pharmacological and psychosocial approaches, substance misuse treatment, environmental modifications, and when necessary, emergency intervention.10,11 Given the multiple and complex challenges associated with this population, practitioners are encouraged to adapt and individualize treatment and prevention practices.11 In terms of pharmacological intervention, SSRIs, namely sertraline, have been found to be effective an first line treatment for depression.12 In addition to treating depressive symptoms, SSRIs may also improve other frequently reported TBI symptoms, such as irritability, aggression and poor impulse control. When prescribing medications following TBI, a conservative, approach to dosing (ie, “low and slow”) is recommended as individuals with TBI may be sensitive and susceptible to medication adverse effects.13 Psychosocial interventions, such as support groups, strengthening family relationships, and involving patients in social skills training have been effective in decreasing feelings of loneliness and isolation.10 In a controlled trial, Simpson et al randomized a group of adults with severe TBI and severe hopelessness or suicidal ideation to either an intervention group (n=8) or a wait list control group (n=9).14 The participants in the intervention group received a 20-hour, manualized cognitive behavior therapy program. Interventions assisted participants to live a positive lifestyle by promoting expression of thoughts and feelings, reframing/reappraising disturbing situations, acquire adaptive coping skills (ie, problem-solving, asking for help, etc), and promoting posttraumatic growth by making meaning of the brain injury. The treatment group demonstrated a significant reduction in hopelessness, and this effect was maintained at 3-month follow-up for 75% of participants. Given that substance abuse, particularly alcohol abuse, is a risk factor for suicide attempt, substance abuse treatment can be an important component in a suicide prevention plan.9,10 Environmental modifications, such as restricting access to sharps, guns, toxic chemicals, and other means of self-harm, has been shown to be effective in reducing suicide.10 Use of “No Harm Contracts” could be an appropriate intervention for patients with brain injury. A no harm contract is an intervention intended to prevent self-harm.15 It is a written agreement between a clinician and a patient (ie, person receiving psychotherapy or mental health services) whereby the patient promises not to harm themself. Reviewers of the literature on the efficacy of No Harm Contracts argue a lack of quantitative evidence to support the use of such contracts.16 Conceptual and ethical issues related to the use of No Harm Contracts include: Potential for coercion from the clinician for their own protection (ie, legal protection) Patients who agree to such contracts remain at high risk for suicide Contracts can falsely reassure clinicians which may result in decreased attention and concern about a patient’s suicide risk A significant percentage of patients that signed a contract either attempted or completed suicide However, alternatives to No Harm Contracts have shown limited or questionable utility. Some clinicians believe that the absence of extensive research concerning the efficacy of contracts in the prevention of suicide should not be used to conclude that contracts have no therapeutic benefit or usefulness in treating suicidal patients. Some potential benefits could include: A patient’s willingness to engage in a contract can be a useful tool in assessing suicidality A contract allows the clinician an opportunity to express genuine concern and commitment to the patient which may bolster the therapeutic relationship Emphasizing a shared common goal may increase the connection between therapist and patient and provide a calming effect The contract may also provide an opportunity for the patient to safely explore self-destructive feelings and meanings of life and death. Like all therapeutic interventions and techniques, those that address suicidality must be tailored to each patient. Note: This article originally appeared on Medscape .

TOPLINE: More time spent exposed to screens is associated with a higher risk for myopia in children and adolescents; the use of computers and televisions appears to have the most significant effects on eye health. METHODOLOGY: Researchers conducted a meta-analysis of 19 studies involving 102,360 children and adolescents to assess the association between screen time and myopia. Data were collected from studies published before June 1, 2023, in three databases: PubMed, Embase, and Web of Science. Screen time was categorized by device type, including computers, televisions, and smartphones, and analyzed using random or fixed-effect models. The analysis included both cohort and cross-sectional studies. TAKEAWAY: High exposure to screen time was significantly associated with myopia in both cross-sectional (odds ratio [OR], 2.24; 95% CI, 1.47-3.42) and cohort studies (OR, 2.39; 95% CI, 2.07-2.76). In cohort studies, each extra hour per day spent using screens increased the risk for myopia by 7% (95% CI, 1.01-1.13). Subgroup analyses revealed significant associations between myopia and screen time on computers (OR, 8.19; 95% CI, 4.78-14.04) and televisions (OR, 1.46; 95% CI, 1.02-2.10), whereas time spent using smartphones was not significantly associated with myopia. IN PRACTICE: "With the development of technology and GDP [gross domestic product], educational pressure may lead students to use screen devices such as smartphones and computers for long periods of time to learn online courses, receive additional tutoring or practice, and increase the incidence of myopia," wrote the authors. LIMITATIONS: The majority of the studies included were cross-sectional, which cannot establish causality. High heterogeneity was found among the included studies, possibly due to differences in research design, population characteristics, and exposure levels. Some studies did not adjust for important confounding factors such as outdoor activities. Note: This article originally appeared on Medscape .

I'm going to talk about improving the physical health of people living with severe mental illness such as schizophrenia, bipolar disorder, and severe depression. The association between mental illness and physical health is both fascinating and very, very important. The ancient Greek philosopher Plato famously said that the greatest mistake in the treatment of diseases is that there are physicians for the body and physicians for the soul, although the two cannot be separated. The unarguable and unavoidable truth is that there is a huge excess mortality among those living with severe mental illness. People living with severe mental illness die, on average, 15-20 years earlier than the general population. Most of this excess mortality, around 75%, is due to common physical comorbidities such as cardiovascular disease, respiratory disease, diabetes, and cancer, rather than suicide. If these conditions were diagnosed and managed at an earlier stage, outcomes could be improved. Tragically, this mortality gap continues to widen, driven particularly by cardiovascular disease. Over the past 25 years, the incidence of cardiovascular disease has fallen in the general population, whereas it has not declined at all in people living with severe mental illness. Why is this the case? Severe mental illness often presents in younger individuals and can lead to unhealthy lifestyles, social disadvantage, and the use of antipsychotic medication with adverse cardiometabolic effects. As such, risk factors for cardiometabolic disease appear much earlier in people living with severe mental illness than in the general population. For example, by the age of 40 years, people with severe mental illness are three to four times more likely to have features of the metabolic syndrome compared with the general population. Type 2 diabetes is two to three times more frequent, eventually affecting 10%-15% of people living with severe mental illness. Cardiovascular disease is three times more frequent in those living with schizophrenia. Although it is challenging to address the social determinants of health, such as income, education, unemployment, and housing, we as healthcare professionals can pay closer attention to cardiometabolic risk factor management in people living with severe mental illness from the point of diagnosis rather than waiting, as usual, until the middle ages. This recalls another, more recent quote by Julian Tudor-Hart, a Welsh GP, who sadly died in 2018. He coined the famous inverse care law back in 1971. The availability of good medical or social care tends to vary inversely with the need of the population served. Perversely, those who need healthcare most, such as our patients living with severe mental illness, are least likely to be able to access it. What can we do in primary care? We need to consider cardiometabolic disease prevention from point of diagnosis. The late UK professor Helen Lester, a GP and academic, encouraged us not to just screen but intervene. During 2012, she contributed toward the Positive Cardiometabolic Health Resource, an intervention framework for people experiencing psychosis and schizophrenia. This was recently updated during 2023. This resource gives recommendations relating to the monitoring of physical health in people experiencing psychosis and schizophrenia. Note: This article originally appeared on Medscape .

Extended-release injectable naltrexone combined with extended-release oral bupropion (NTX + BUPN) for moderate or severe methamphetamine use disorder was associated with a significant decrease in use of the drug, a new study showed. Investigators leading the randomized clinical trial found a 27% increase in negative methamphetamine urine tests in the treatment group — indicating reduced use — compared with an 11% increase in negative urine tests in control participants. "These findings have important implications for pharmacological treatment for methamphetamine use disorder. There is no FDA-approved medication for it, yet methamphetamine-involved overdoses have greatly increased over the past decade," lead author Michael Li, MD, assistant professor-in-residence of family medicine at the David Geffen School of Medicine at UCLA, Los Angeles, said in a news release. The study was published online on June 10 in Addiction . Methamphetamine use has increased worldwide, from 33 million users in 2010 to 34 million in 2020, with overdose deaths rising fivefold in the United States over the past decade, the authors wrote. A previous open-label study of NTX + BUPN showed efficacy for treating severe methamphetamine use disorder, and NTX and BUPN have each shown efficacy separately for this indication. This new study is the second phase of the multicenter ADAPT-2 trial, conducted between 2017 and 2019 in 403 participants with methamphetamine use disorder. In the first stage, 109 people received NTX + BUPN and 294 received placebo. The treatment group received extended-release NTX (380 mg) or placebo as an intramuscular injection on weeks 1, 4, 7 and 10. Extended-release BUPN or placebo tablets were administered weekly, with BUPN doses starting at 150 mg on day 1 and increasing to 450 mg by day 3. At week 13, participants received a tapering dose for 4 days before discontinuing. As previously reported by Medscape Medical News , the two-drug combo was effective at reducing methamphetamine use at 6 weeks. The current analysis measured change in methamphetamine use during weeks 7-12 of the trial and in posttreatment weeks 13-16. Participants in the intervention group during stage 1 showed an additional 9.2% increase (P = .038) during stage 2 in their probability of testing negative for methamphetamine. This represented a total increase of 27.1% in negative urine tests across the complete 12 weeks of treatment, compared with a total 11.4% increase in negative tests in the placebo group. The 12-week increase in methamphetamine-negative urine tests in the intervention group was 15.8% greater (P = .006) than the increase in the placebo group. There was no significant change in either group at posttreatment follow-up in weeks 13-16. "Our findings suggest that ongoing NTX + BUPN treatment yields statistically significant reductions in methamphetamine-use that continue from weeks 7 to 12," the authors wrote. The lack of change in methamphetamine use from weeks 13-16 corresponds to the conclusion of treatment in week 12, they added. It "remains to be determined "whether continued use of NTX + BUPN treatment past 12 weeks would yield further reductions in use," the authors wrote, noting that prior stimulant use disorder trials suggest that change in use is gradual and that sustained abstinence is unlikely in merely 12 weeks of a trial. Rather, it is dependent on treatment duration. "This warrants future clinical trials to quantify changes in methamphetamine use beyond 12 weeks and to identify the optimal duration of treatment with this medication," they concluded. The study was funded by awards from the National Institute on Drug Abuse (NIDA), the US Department of Health and Human Services; the National Institute of Mental Health, and the O'Donnell Clinical Neuroscience Scholar Award from the University of Texas, Southwestern Medical Center. Alkermes provided Vivitrol (naltrexone for extended-release injectable suspension) and matched placebo free of charge for use in this trial under a written agreement with NIDA. Li reports no relevant financial relationships. The other authors' disclosures are listed on the original paper. Note: This article originally appeared on Medscape .

TOPLINE: Rates of cardiorespiratory depression are not significantly different between patients with severe agitation treated with olanzapine alone and those receiving a combination of olanzapine and a benzodiazepine. METHODOLOGY: Researchers assessed 693 patients with severe agitation in an emergency department who received intramuscular or intravenous olanzapine coadministered with either a second parenteral dose of olanzapine (n = 549) or a benzodiazepine (n = 144) within 60 minutes of each other between January 2017 and May 2019. The primary outcome was tracheal intubation. The secondary outcomes included hypoxemia (oxygen saturation less than 90%), hypotension (systolic blood pressure less than 90 mmHg), and death during hospitalization. TAKEAWAY: No significant difference in tracheal intubation rates was found between the olanzapine-only group and the olanzapine plus benzodiazepine group (3.8% vs 3.5%; difference, 0.3%; 95% CI, −3.0% to 3.7%). Respiratory depression was the reason for tracheal intubation in 10 out of 21 patients in the olanzapine-only group and 4 out of 5 patients in the olanzapine plus benzodiazepine group. The occurrence rate of hypotension was 9% in both groups. Among patients with a detectable alcohol concentration, 3.6% were intubated following two doses of olanzapine, and 6.4% received olanzapine plus a benzodiazepine. IN PRACTICE: "Our data suggest that if olanzapine monotherapy is not effective in this instance, rescue therapy with parenteral benzodiazepines is safe even if coadministered within 60 minutes," wrote the authors of the study. Note: This article originally appeared on Medscape .