Premature opioid-related deaths doubled in Canada after the onset of COVID-19 pandemic, and more than one in four deaths occurred in young adults, a new study suggested. "The intersection of the COVID-19 pandemic with the drug toxicity crisis in Canada has created an urgent need to better understand the patterns of opioid-related deaths across the country to inform targeted public health responses," the study authors wrote. Some Canadian provinces were disproportionately affected by the crisis, they noted. For example, in Alberta, close to half of all deaths among people aged 20-39 years were opioid-related. "Although the finding that the early loss of life was increasing over time was expected, the magnitude of this burden across Canada surprised me," lead author Shaleesa Ledlie, MPH, a PhD candidate at the Leslie Dan Faculty of Pharmacy of the University of Toronto, Toronto, Ontario, Canada, told Medscape Medical News. In addition to the increase in Alberta, she said, "in Manitoba, opioid-related death rates and the associated years of life lost increased almost fivefold between 2019 and 2021. This really reinforces the urgency of this issue across Canada and identifies regions where focused attention might be warranted." The study was published online on April 15 in Canadian Medical Association Journal. Significant Increases Researchers conducted a repeated cross-sectional analysis of accidental opioid-related deaths from 2019 through 2021 in nine Canadian provinces and territories. All provinces and territories for which age- and sex-stratified data were available at the time of the study were included: British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec, New Brunswick, Nova Scotia, and the Northwest Territories. These areas represent 98% of Canada's population. Deaths were determined to be accidental or intentional by the coroner or medical examiner in each province or territory who investigated the death, according to Ledlie. The primary outcome was the burden of premature opioid-related death, measured by potential years of life lost (YLL). The secondary outcome was the proportion of deaths attributable to opioids. Overall, the annual YLL from opioid-related deaths doubled during the study period, from 3.5 YLL per 1000 population in 2019 to 7.0 YLL per 1000 in 2021. In 2021, the highest burdens of death were observed among men (9.9 YLL per 1000) and young adults aged 20-29 years (12.8 YLL per 1000) and 30-39 years (16.5 YLL per 1000). More than 70% of all opioid-related deaths occurred among men each year (73.9% in 2021), and about 25% of deaths occurred among people between the ages of 30 and 39 years (29.5% in 2021). Geographic Variation The annual increases by age and sex in each province and territory were generally consistent with the overall analysis. The observed changes in YLL over time varied geographically, however. They ranged from a 0.8-fold decrease in Nova Scotia (1581 YLL in 2019 to 1324 YLL in 2021) to a 4.7-fold increase in Manitoba (2434 YLL in 2019 to 11,543 YLL in 2021). In 2021, the rate of YLL ranged from a low of 1.4 per 1000 in Nova Scotia to a high of 15.6 per 1000 in Alberta, whereas the absolute number of YLL ranged from 93 in the Northwest Territories to 111,633 in Ontario. Between 2019 and 2021, the average percentage of all deaths attributed to opioids increased in all age groups. In 2019, 1.7% of deaths among people younger than 85 years were related to opioids. This proportion increased to 3.2% of deaths in 2021. The largest relative increase between 2019 and 2021 (50.3%) was among young people. Opioid-attributable deaths increased from 19.3% to 29.0% among those aged 30-39 years. This change was followed by a 48.0% increase among those aged 20-29 years from 19.8% to 29.3%. The authors noted that the study was limited by their inability to examine four provinces and territories for which the numbers of opioid-related deaths were suppressed because of small counts (ie, < 5). However, sensitivity analyses suggested that the demographic distribution of these deaths followed a pattern like that of the overall results. More Information Needed Commenting on the study for Medscape Medical News, S. Monty Ghosh, MD, MPH, an assistant professor at the University of Alberta, clinical assistant professor at the University of Calgary, and co-medical lead of Alberta Health Services' Rapid Access Addiction Medicine program in Calgary, said, "The study was fairly robust in its evaluation. Their approach statistically is sound and makes sense, given the quality of data they received." Ghosh did not participate in the analysis. It would be important to know whether the premature deaths were polysubstance related, he noted. "More nuanced data in Alberta demonstrated that most of the deaths are related to polysubstance use on top of fentanyl. This includes alcohol, meth, as well as substance contaminants such as benzodiazepines, and more lately (outside of the research period), xylazine." Furthermore, Ghosh added, "It would be good to see more demographic information around the youth in Alberta. For instance, were they housed or unhoused? Are they Indigenous? Anecdotally, we know that blue-collar workers, especially those in Alberta who work in construction and oil rigs, have a disproportionate rate of substance use and at times substance death. This was seen in British Columbia and Ontario." What's Being Done The government of Alberta is responding to these data, said Ghosh. For example, in 2022, specialized funding was provided to enable young adults to access gold-standard opioid agonist treatment. The treatment was rolled out through Alberta's Virtual Opioid Dependency Program (VODP) and other community-based addiction programs. "This [program] still needs to be more focused on homeless youth, however, who may not have access to technology or other resources." Furthermore, the government recently announced a $1.55-billion plan to continue building the Alberta Recovery model, he said. "This is the largest investment seen in our province. Safer supply or prescribed alternatives is very controversial in Alberta and thus is not an option available to this population." In addition, he said, the Ministry of Seniors and Community Social Services recently began "coordinated work with other ministries to support vulnerable and equity-deserving populations around this issue, including creating navigation centers for housing, income support, and access to treatment through the VODP." Ledlie noted that various policies and programs have been developed in response to the ongoing drug toxicity crisis. Some were included in a recent review that her team conducted to summarize the evidence from Canadian safer opioid supply programs. "We found that in general, these programs had positive impacts on clients, including reduced rates of opioid toxicities and improvements in quality of life." "Because most healthcare is coordinated at the provincial or territorial level, the investments into, and accessibility of, treatment and harm-reduction services tend to vary across Canada," she said. "Even in regions where these programs exist, we know that they are not always accessible for various reasons, such as a lack of resources preventing widespread expansion and geographic barriers in more remote and rural regions." "One example of a simple yet life-saving harm reduction measure that has been effectively implemented by most provincial and territorial governments is the availability of publicly funded naloxone kits," she added. "Given the widespread societal impacts of opioid toxicities described in our study, we believe it is pivotal for all levels of government to coordinate to ensure equitable access to evidence-based services across the country, while still providing the opportunity to tailor and adapt those responses to the unique needs of local communities." The study was supported by grants from the Ontario Ministry of Health and the Canadian Institutes of Health Research. Ledlie is supported by an Ontario Graduate Scholarship and the Network for Improving Health Systems Trainee Award. Ledlie and Ghosh declared no relevant financial relationships. Note: This article originally appeared on Medscape

Keypoint: Current behavioral therapies may not be effective for anxious-depressed pediatric patients with a history of trauma. Brief behavioral therapy (BBT) is broadly effective for pediatric patients with depression and anxiety. However, BBT does not outperform assisted referral to outpatient community care (ARC) among children and adolescents with pediatric trauma exposure. These findings were published in NPJ Mental Health Research. Although anxiety and depression are the most common psychiatric disorders among children and adolescents, these disorders frequently go untreated before adulthood. Recently, evidence-based transdiagnostic psychotherapies have been developed in the hopes of increasing access to treatment among pediatric patients. However, little is known about whether these therapies are effective in children and adolescents who have been exposed to trauma. Therefore, researchers conducted a study to determine if trauma exposure and clinically significant depression were moderators of BBT treatment outcomes among pediatric patients with anxiety. In this randomized controlled trial, the researchers recruited pediatric patients with an anxiety disorder and/or depression who were not currently receiving treatment for their disorder(s). Clinical diagnoses were confirmed at baseline using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), the Children’s Depression Rating Scale-Revised (CDRS-R), and Diagnostic and Statistical Manual of Mental Disorders, Fourth Revision (DSM-IV), criteria. Participants who were experiencing suicidality, did not speak English, and/or had other comorbid disorders were excluded from the study. The researchers used the Clinical Global Impressions severity scale (CGI-S), the Children’s Global Assessment Scale (CGAS), and the Pediatric Anxiety Rating Scale (PARS) to evaluate clinical response, functioning, and anxiety symptoms at 16-week and 32-week follow-up appointments. A total of 175 children and adolescents (aged 8 to 16 years) were included for analysis and the researchers randomly assigned participants to BBT (n=89) or ARC (n=86). At baseline, 46.3% of participants reported exposure to at least 1 traumatic event. Among participants with a history of trauma, 48.1% were exposed to more than 1 type of traumatic event. The most common single types of traumatic events were car/other accidents (32.1%), domestic violence (25.9%), natural disaster (18.5%), fire (14.8%), physical abuse (8.6%), violent crime (6.2%), and victim or witness to sexual abuse (2.5%). At the 16-week follow-up, the researchers found a significant main effect of the treatment group favoring BBT over ARC for treatment response (P =.031) and anxiety symptoms (P =.013). However, there was also a significant 3-way interaction between treatment group, comorbid depression, and trauma exposure. These findings indicated that a history of pediatric trauma exposure ameliorated the significant effect of BBT over ARC for treatment response and anxiety. At 32 weeks, BBT again outperformed ARC for treatment response (P =.013) and anxiety (P <.001). The researchers also observed a significant 3-way interaction between treatment group, comorbid depression, and trauma exposure for anxiety symptoms, in which BBT was not significantly different than ARC for anxiety symptoms. The researchers noted, “Although there were differences in outcomes across the patterns of comorbid depression and trauma exposure, the significant positive effect of BBT over ARC was generally robust, except for [patients] who were anxious, depressed, and endorsed a history of trauma exposure.” Study authors concluded, “This is a critically important subgroup of youths, given the high prevalence of trauma exposure in the community, the strong overlap between trauma exposure and the presence of depression, and the high comorbidity of anxiety and depression.” Study limitations include an underpowered sample size for analyses of 3-way interactions and the use of a binary variable for trauma exposure.

Providing care to individuals with borderline personality disorder (BPD) within inpatient medical settings can bring unique challenges for patients and medical teams. Individuals with BPD are more likely to have limited medical literacy, engage in challenging behavior and verbal altercations with their medical team, and be psychiatrically misdiagnosed. They also often are considered high-risk patients in hospital settings due to the increased possibility of intentional or unintentional self-harm behaviors. These include overdoses, impulsive verbal arguments, unprotected sexual activity, poor medication and treatment adherence, nonsuicidal self-injurious behaviors, and suicide attempts. These factors can be barriers for patients with BPD when they undergo admission, as medical units are less equipped to adequately address primarily psychiatric symptoms. This can then affect the care of other hospitalized patients as well as staff morale. Consultation-liaison (C-L) psychiatry assumes the pivotal role in correctly discerning the presence of BPD, facilitating effective communication between patients and medical teams, and providing effective treatments as well as behavioral management during these patients’ admissions. There are unique considerations during an obstetric hospitalization. Clinicians need to incorporate pregnancy and lactation safety data in their treatment recommendations and to be mindful of attachment and infant safety. BPD can impact parenting behaviors and influence infant attachment in mother-baby dyads where the mother is diagnosed with BPD.1 Women with BPD are at elevated risk for comorbid psychiatric disorders, including mood and anxiety disorders, eating disorders, substance abuse histories, and trauma/stressor-related disorders. Navigating disposition planning can be a challenge, as postpartum patients are expected to be hospitalized for a brief time. This requires rapid evaluation and treatment planning to support a safe discharge home for mother and baby. For those requiring inpatient psychiatric admission, it may be challenging to find a unit willing to admit a pregnant or breastfeeding patient. Providing care to individuals with borderline personality disorder (BPD) within inpatient medical settings can bring unique challenges for patients and medical teams. Individuals with BPD are more likely to have limited medical literacy, engage in challenging behavior and verbal altercations with their medical team, and be psychiatrically misdiagnosed. They also often are considered high-risk patients in hospital settings due to the increased possibility of intentional or unintentional self-harm behaviors. These include overdoses, impulsive verbal arguments, unprotected sexual activity, poor medication and treatment adherence, nonsuicidal self-injurious behaviors, and suicide attempts. These factors can be barriers for patients with BPD when they undergo admission, as medical units are less equipped to adequately address primarily psychiatric symptoms. This can then affect the care of other hospitalized patients as well as staff morale. Consultation-liaison (C-L) psychiatry assumes the pivotal role in correctly discerning the presence of BPD, facilitating effective communication between patients and medical teams, and providing effective treatments as well as behavioral management during these patients’ admissions. There are unique considerations during an obstetric hospitalization. Clinicians need to incorporate pregnancy and lactation safety data in their treatment recommendations and to be mindful of attachment and infant safety. BPD can impact parenting behaviors and influence infant attachment in mother-baby dyads where the mother is diagnosed with BPD.1 Women with BPD are at elevated risk for comorbid psychiatric disorders, including mood and anxiety disorders, eating disorders, substance abuse histories, and trauma/stressor-related disorders. Navigating disposition planning can be a challenge, as postpartum patients are expected to be hospitalized for a brief time. This requires rapid evaluation and treatment planning to support a safe discharge home for mother and baby. For those requiring inpatient psychiatric admission, it may be challenging to find a unit willing to admit a pregnant or breastfeeding patient. BPD and Trauma Patients with BPD are more likely to endorse a trauma history, especially prior experiences of repeated child abuse and neglect and instances of sexual trauma.4 Trauma is a known contributor to emotional lability, dissociative symptoms, and interpersonal difficulties. Patients with a trauma history and BPD traits are at higher risk for developing comorbid posttraumatic stress disorder. During the peripartum period, there are many opportunities for patients with a trauma history to experience retraumatization. Many aspects of routine care and pregnancy include sensitive exams (eg, cervical checks), physical discomfort (eg, hyperemesis, pelvic floor changes), and personal questions (eg, sexual history, birth preparation). For patients with a trauma history, these experiences can be more distressing. The underlying personality traits of BPD can lead to maladaptive behaviors employed to cope with the distress of these experiences. Researchers are starting to recognize that childbirth itself can be a potential trauma for peripartum patients. Patients with BPD are at heightened risk for poor outcomes if they experience a loss of control during the delivery, require unanticipated or emergency intervention, experience medical complications affecting themselves or their newborn, or perceive their medical team to be uncaring or even actively harmful. Medical professionals can help by maintaining a calm, firm communication style and speaking from an emotionally empathic position. A trauma-informed approach is critical in supporting these patients before, during, and immediately after their delivery, with clinicians prioritizing clear communication and informed consent early in the medical decision-making process. BPD and Bipolar Disorder BPD is associated with increased likelihood for a co-occurring bipolar I or II disorder. When both are present, it suggests worsened overall functioning, heightened risk of suicide, and higher psychiatric acuity.5,6 The significant overlap in symptoms (eg, emotional lability, suicidal behavior, and impulsivity) can lead to the misdiagnosis of bipolar disorder in patients with BPD. It is critical to correctly identify when bipolar disorder is present, as the gold standard of treatment for bipolar disorder—psychopharmacological treatments with adjunctive psychotherapy—differs from BPD, where behavior management and coping skills take precedence over medication. Furthermore, patients with BPD are at heightened risk of polypharmacy, despite minimal evidence that medication is effective in treating BPD. In the perinatal period, it is recommended that clinicians thoroughly assess for individual and family history of bipolar disorder, as it is a known risk factor for the development of postpartum psychosis (PPP) following delivery.9 PPP is a medical emergency that can progress rapidly, develops most often within 10 days after delivery, and carries an acute risk of infanticide and suicide. One of the most used questionnaires to identify patients with bipolar disorder, the Mood Disorder Questionnaire, has been shown to have a high false-positive rate in the BPD population.11 It is critical to correctly differentiate bipolar disorder from BPD within the peripartum population with thorough diagnostic interviewing to maximize treatment gains and mitigate risks from medication management. A patient who presents with self-reported or even a historical diagnosis of bipolar disorder, as identified through a chart review, might be unnecessarily exposed to a mood stabilizer if this diagnosis is incorrectly assigned. Case Example, Part 2 Upon further evaluation, it was determined that the patient’s acute risk of self-harm was high. She was placed on a safety watch, and a search for an available inpatient psychiatry bed was started. Over the next several days, her behavior on the unit escalated, with the patient engaging in threatening and violent behavior toward hospital staff. Some examples include: Requiring that she receive care from only a select group of staff. When other staff attempted to provide care, she began yelling at staff to leave and shouting expletives. She yelled racial insults at non-White staff. Typically, the charge nurse or unit manager moved staff around to give the patient her preferred staff member. The staff member on the receiving end of these interactions often was distressed afterward. Telling staff that she would hurt them when they began assessments related to her housing or talking about her plans for the baby. She occasionally followed up these statements by throwing items in her room or shoving furniture in the room toward them. Making suicidal statements daily. These typically resulted in immediate outreach to C-L psychiatry and significant distress for the staff, who felt ill equipped to manage suicidal patients. C-L psychiatry made treatment recommendations with the goal of minimizing problematic behaviors, supporting staff, and increasing the patient’s engagement in her medical treatment. Although medication is not the first line of treatment for BPD traits, several short-acting medications are recommended to manage acute outbursts and agitation. The bulk of the treatment for the patient included implementing a behavior plan, along with individual therapy sessions 4 to 5 times a week. This behavior plan was created to provide clear guidance to staff. The goals of therapy were to build rapport with the patient, provide emotional support, and teach appropriate coping and communication skills. Clinical Implications Patients with BPD are at a higher risk of medical hospitalization, during which they are more likely to engage in self-harming behaviors, require constant observation for safety, and attempt or complete suicide.12,13 These behaviors are challenging to treat in the medical setting and can complicate or undermine medical care. For patients with BPD, symptoms are best managed with therapeutic intervention focused on teaching appropriate coping skills, along with effective behavior management techniques from those around them. Treatment Recommendations Excluding clinical presentations where there is a comorbid mood or anxiety disorder, long-term medication management is not recommended for these patients, as personality disorders are inherently pervasive and global. The maladaptive behaviors seen in this population respond robustly to behavior-based psychotherapies (eg, dialectical behavior therapy). Goals of therapy should be triaged across 4 stages beginning with minimizing self-harming behaviors and increasing treatment adherence. Following clinical improvement, the plan concludes with a focus on creating a meaningful and rich life (Table). For clinicians caring for hospitalized obstetric patients with BPD, it is most likely that these patients will require the immediate skill-building and distress tolerance components in the initial stage of treatment. Treating clinicians should prioritize the following: First, psychiatry should take a proactive approach, ensuring that patients are seen near daily to minimize the potential for secondary gains from reactive psychiatry consults occurring after patients engage in problematic behavior. Second, psychiatry should model direct, clear, and consistent communication for both the team and the patient. Clinicians should ensure that patients understand what to expect from all team members (ie, say what you mean and do what you say). Third, prioritize patient safety in session content by working on minimizing self-harm behaviors (eg, suicide attempts, aggression toward others) and increasing treatment adherence (eg, attending required appointments and tests). Finally, the therapeutic relationship can be used to build a positive association with mental health treatment for the peripartum patient with BPD, increasing the likelihood of successful outpatient treatment upon eventual discharge. This is helpful in managing symptoms of BPD and supporting a secure infant attachment in the postpartum period. Behavior Planning As staff on medical units receive significantly less exposure to and training in psychiatric symptom management, C-L psychiatry is a critical resource for medical teams. Compared with other medical units, obstetric units see fewer acute psychiatric emergencies due to higher patient turnover, more “healthy” patients, and shorter admissions. The presence of newborns on the unit also adds an additional team to coordinate with, along with the responsibility of ensuring a safe discharge for the birthing parent and the newborn. All these factors can lead to increased uncertainty about how to manage problematic behaviors in an obstetric unit in a way that is consistent and unbiased and supports patient autonomy. Behavior planning is an effective tool for staff and providers of these patients and should be based on the principles of behaviorism. When creating a behavior plan, there are several components to consider. First, the clinician should meet with unit leadership, nursing, and medical team decision makers to elicit goals of care, barriers to discharge, and interpersonal concerns and to create a unified treatment plan. Second, the clinician needs a good understanding of the function of the patient’s behavior. In other words, why is the patient engaging in problematic behaviors—what are they hoping to gain or avoid? With this answer, the clinician can then guide staff in teaching more appropriate ways to support the patient in getting needs met. Behavior plans should clearly label target behaviors using observable and specific language. For example, the target behavior “patient will not get mad at staff” is unclear and hard to measure or intervene upon. This target behavior can be more specific: “patient will not throw items at staff, use expletives or racially derogatory terms, or speak to staff at a loud volume.” This target behavior could be further improved by making a language shift that explicitly communicates behavior expectations such as “the patient will speak at an appropriate volume using respectful, nonderogatory language.” Consequences should be clearly communicated and consistently implemented across all staff and settings. Behaviorism divides consequences as either a reinforcer (outcome that makes a behavior more likely) or a punisher (outcome that makes a behavior less likely). When a behavior’s function is identified, the consequence should be readily identified. For example, if the patient is engaging in verbally aggressive behavior to see a favorite staff member and have the team round on her at her preferred time, the consequence should directly address those variables. If looking to reinforce appropriate behaviors, allow the patient to do those things after she engages appropriately. Notably, the most effective behavior planning prioritizes reinforcement and limits the use of punishment solely to behaviors that are harmful to the patient and/or others. Reinforcement is the most effective tool in teaching new, robust behavioral repertoires while supporting and respecting patient autonomy. The previously outlined target behavior could include a reinforcer of allowing the patient a choice of when she would like the team to round on her or extra time with a preferred staff member after a period without verbal aggression. Finally, behavior plans work best when they focus on a single behavior or a small group of behaviors. Prioritize behaviors that support the patient’s self-identified treatment goals, promote patient health and well-being, minimize treatment nonadherence, and reduce harm to staff.

Keypoint: Children living in poverty experience higher rates of daily screen time. An average daily screen time of 2 hours or more is associated with lower psychological well-being among preschool-aged children in the United States, according to study findings published in the JAMA Network Open. High screen time (HST) was particularly prevalent among children living in poverty. Previous research has demonstrated that screen time among young children has increased globally, especially at the onset of the COVID-19 pandemic. However, relatively little is known about whether these levels have remained elevated in preschool-aged children in the US across race, ethnicity, and family income. To this aim, investigators conducted a cross-sectional, population-based survey study using data collected between 2018 to 2021 from the National Survey of Children’s Health (NSCH) to evaluate screen time among US children 6 months to 5 years of age (as reported by their primary caregivers). Primary caregivers reported each child’s daily screen time and the investigators used the American Academy of Pediatrics (AAP) screen time recommendations to define HST as 1 hour or greater for children 6 months to 1 year of age, and at least 2 hours per day for children 2 to 5 years of age. The primary outcome of interest was psychological well-being, assessed using 4 NSCH items in the survey that included questions on flourishing and externalizing behaviors. A total of 48,775 participants were included for analysis, 50.7% of which were girls. Overall, 50.7% (95% CI, 49.7%-51.7%) of children had HST. In 2019, the overall proportion of children with HST was 49.2% (95% CI, 47.0%-51.5%). This value increased to 55.3% (95% CI, 53.4%-57.2%) in 2020 during the pandemic and returned to pre-pandemic levels in 2021 (50.0%; 95% CI, 48.3%-51.6%). These values were even more pronounced among children living in poverty, as the proportion of children with HST was 60.9% (95% CI, 55.4%-66.4%) in 2020 and remained elevated at 58.9% (95% CI, 53.7%-64.1%) in 2021. The investigators found that HST was associated with worse psychological well-being among young children. Children 3 to 5 years of age had lower odds of flourishing if they had an average daily screen time of 2 hours (adjusted odds ratio [aOR], 0.81; 95% CI, 0.66-0.99), 3 hours (aOR, 0.68; 95% CI, 0.52-0.88), or 4 or more hours (aOR, 0.53; 95% CI, 0.42-0.69), relative to children with only 1 hour of daily screen time. No association was found between daily screen time and flourishing among children 6 months to 2 years of age. A similar trend was observed with externalizing behaviors. Relative to an average daily screen time of 1 hour, the adjusted externalizing behavior score among children 3 to 5 years of age was increased by 0.5 (95% CI, 0.3 to 0.8) points with 2 hours of daily screen time, 1.3 (95% CI, 1.0 to 1.6) points higher with 3 hours, and 2.1 (95% CI, 1.7 to 2.5) points higher with 4 or more hours per day. By race/ethnicity, the overall proportion of children with high screen time was highest among non-Hispanic Black participants (64.4%), followed by Hispanic participants (55.8%), and non-Hispanic White participants (45.0%). The investigators concluded, “These findings highlight urgent needs to provide support for healthy screen use to families with young children.” Study limitations include the use of proxy-reported measures for screen time and psychological well-being and incremental vs continuous measurement of screen time. Additionally, there was a lack of data on the type of screen content children were consuming. Note: This article originally appeared on Psychiatry Advisor

Keypoint: In a meta-analysis, older and female children were likely to recall acute pain more intensely than was experienced, especially in a clinical context. Children aged 18 years and younger tend to overestimate pain memory when comparing the experienced vs recalled intensity of acute pain, with only sex and age predictive of pain memory accuracy, according to study results published in Pain. Following PRISMA guidelines, investigators conducted a systematic review and meta-analysis with a meta-regression to analyze accuracy of the memory of pain and the variables that may influence it in children with acute, experimental, and chronic pain. They searched 5 databases (MEDLINE/PubMed, Embase, CINAHL, Web of Science, and APA PsychInfo) from inception to February 11, 2022, and performed a statistical analysis using RStudio software (Rstudio, PBC, Boston, Mass.) and shared the Rscript and data on the Open Science Framework. The quality of the evidence was evaluated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) framework. Standardized mean differences (SMDs) and 95% CIs for continuous variables were calculated to assess clinical effects, with subgroup analyses using a fixed-effects model conducted to discern differences in pain-related context (clinical vs experimental). Additional robustness checks included a leave-one-out method and checks for publication bias using visual and quantitative tools. Heterogeneity was assessed using I2 index, Cochran Q test, and meta-regression analysis, with effect-size heterogeneity applied to predict the accuracy of childrens’ memory of pain based on the study characteristics. The review evaluated the accuracy of pain memory in children across various pain types (acute, experimental, and chronic). Meta-regression analysis was used to explore the relationship between memory accuracy and factors such as age, anxiety, fear, and delay in recall. Included in the review were 15 articles with a total of 942 participants, 49% of whom were girls. There were 12 observational studies and 3 randomized controlled trials. Only 3 studies focused on the memory of experimental pain in healthy children. The remaining 12 studies analyzed the memory of acute pain in diverse pediatric populations, including children with leukemia (study not included in meta-analysis because it only provided change scores); children undergoing dental procedures, venipuncture, and vaccinations; and children undergoing surgeries such as tonsillectomy, spinal fusion, and pectus repair. Data on pain memory were collected at various intervals, from 1 day up to 1 year following the pain event. Pain assessments were generally made at baseline, pretreatment/preintervention, immediately or several days post-treatment/postintervention, and at follow-up weeks to months after the given painful treatment/experimental intervention. Despite heterogeneity among studies, there was no evidence of publication bias. Results showed that the recalled intensity of acute pain tended to be overestimated, with a slight standardized mean difference (SMD) of 0.28 (95% CI, 0.08-0.49). This overestimation was more pronounced in clinical contexts (SMD= 0.33; 95% CI, 0.09-0.58), with a statistically significant heterogeneity (P <.01) vs experimental contexts, in which no significant difference between experienced vs recalled pain intensity was found. Age (β=0.08 [95% CI, 0.01-0.14]; F(1,17)=6.68, P =.02, R2*=28.28%) and the proportion of girls (β=0.03 [95% CI, 0.01-0.05]; F(1,17)=7.55, P =.01, R2*=32.62%) were significant predictors of this overestimation, suggesting that older children and a higher percentage of female participants may be more likely to recall pain more intensely than was experienced. Other factors, such as the period of time since pain was experienced, expected and recalled fear, anxiety sensitivity, and trait anxiety, did not significantly predict the accuracy of pain memory. High collinearity between participants’ mean age and the percentage of girls prevented conduction of a multiple meta-regression analysis. The meta-regression analysis did not show a significant relationship between anxiety factors (expected and recalled fear, anxiety sensitivity, and trait anxiety) and the accuracy of pain memories, challenging initial hypotheses. This result might be due to the fact that most of the included studies focused on the sensory dimension of pain, potentially overlooking influence of anxiety on affective aspects of pain. Individual differences in attentional style or coping strategies, not controlled for in several of the evaluated studies, could also have obscured potential relationships. Notably, a significant relationship was identified between the effect size and the mean age of participants and the proportion of girls, suggesting age and gender may influence pain memory bias. Younger children’s cognitive limitations and the unsuitability of certain pain assessment tools for different age groups highlight the need for age-appropriate evaluation methods. In discussing the meta-analysis, the investigators noted that their identification of gender differences in pain memory, with girls often reporting higher pain intensity than boys, aligns with previous findings in adolescents with cancer. These differences, they said, could be attributed to several factors: girls tend to catastrophize pain more than boys, possibly developing a stronger self-concept as individuals who experience pain, which could enhance their pain memories. Additionally, girls may experience more distress or anxiety related to pain, negatively affecting their memory of the pain experience. Stereotypical gender roles, which portray men as less susceptible to pain and women as more sensitive, could also influence these perceptions. This suggests that gender differences in cognitive processing of pain experiences may significantly impact pain memories. Study limitations included that only memory of acute and experimental pain was assessed and not all baselines were assessed immediately after the end of the painful experience. The investigators concluded, “Children showed an overestimation in pain memory between the experienced and recalled intensity of acute pain, especially in a clinical context.” They added, “Furthermore, only gender and age were [accurate] predictors of pain memory. These results highlight the relevance of pain memory to medical practice and future research, as biased pain memory may lead to avoidance in the use of health care systems and the possible development of chronic pain.” Note: This article originally appeared on Clinical Pain Advisor

Keypoint: All-cause mortality risk was lower with stimulant – but not nonstimulant – ADHD medication use. Among individuals with attention-deficit/hyperactivity disorder (ADHD), ADHD medication use is associated with a reduced risk for all-cause mortality and unintentional injuries leading to emergency department (ED) visits, according to study results published in Translational Psychiatry. Previous research has established that ADHD is associated with adverse health outcomes and comorbidities. Although ADHD medications are efficacious in treating ADHD symptoms, relatively little is known about how these medications – both stimulants and nonstimulants – affect mortality and unintentional injuries. To address this knowledge gap, researchers conducted a population-based cohort study using health administrative data in Quebec, Canada. The study evaluated mortality and injury outcomes among individuals with ADHD who were aged 24 years and younger between April 1, 2000, and March 31, 2021. Eligible participants had a physician claim or hospital diagnosis of ADHD. Additionally, the researchers used prescription data to verify ADHD medication use for amphetamine or methylphenidate-based stimulants and nonstimulants. Participants were followed until emigration, death, 25 years of age, or the conclusion of the study. The researchers identified 217,192 participants with ADHD. At study start, 64.2% of the participants were 11 years of age and younger when first diagnosed with ADHD, 64.1% were boys, and 78.5% had a comorbid mental or substance use disorder. The researchers found that the average all-cause mortality rates per 1000 person-years for individuals with ADHD were notably lower during episodes of ADHD medication use (0.26; 95% CI, 0.21-0.32) relative to periods without ADHD medication (0.48; 95% CI, 0.44-0.53). The average rate of injuries leading to ED visits per 1000 person-years was also reduced when individuals were using ADHD medications (91.0; 95% CI, 90.1-91.9) compared with episodes of nonuse (98.3; 95% CI, 97.7-99.0). Hospitalizations due to unintentional injuries showed similar patterns, as the average rates per 1000 person-years were 8.7 (95% CI, 8.5-8.8) without ADHD medication and 7.4 (95% CI, 7.2-7.7) with ADHD medication. These findings were confirmed in hazard ratio models, as the researchers found a reduced risk for all-cause mortality (adjusted hazard ratio [aHR], 0.61; 95% CI, 0.48-0.76) during episodes of ADHD medication use relative to nonuse. This risk reduction was observed during periods of stimulant use alone (aHR, 0.61; 95% CI, 0.48–0.77), but the risk was not reduced with the use of nonstimulants or a combination of stimulants and nonstimulants. The researchers also found that ADHD medication use decreased the risk for unintentional injuries leading to ED admissions (aHR, 0.75; 95% CI, 0.74-0.77) and hospitalizations (aHR, 0.71; 95% CI, 0.68-0.75). This risk reduction was robust across both stimulant and nonstimulant use across both outcomes. Regarding, ADHD medication use also showed a decreased risk with an) compared with no medication use under the public drug plan. This protective effect was similarly observed with stimulant use (aHR 0.76; 95% CI, 0.75–0.77), nonstimulant use (aHR, 0.77; 95% CI, 0.73–0.81), and combined use of stimulants and nonstimulants (aHR, 0.66; 95% CI, 0.62–0.70). The researchers concluded, “The findings of the current study should inform clinical decision making on the choice of starting a pharmacological treatment for ADHD, when a balance needs to be struck between expected benefits and possible risks.” Study limitations include the reliance on prescription claims for ADHD medication use (without verifying medication adherence), potential residual confounding, and a lack of generalizability to other populations or healthcare systems. Note: This article originally appeared on Psychiatry Advisor

Keypoint: Offspring of parents with AUD are at increased risk for ADHD. When evaluating the familial vulnerability to and genetics of alcohol use disorder (AUD), investigators found that offspring of parents with AUD were at increased risk for AUD, drug use disorder, attention-deficit/hyperactivity disorder (ADHD), depression, and anxiety. These results were published in the American Journal of Psychiatry. Although environmental factors play a significant role in the development of AUD, research has consistently demonstrated a strong genetic component. Previous studies have shown that individuals with a family history of AUD are at a higher risk of developing the disorder themselves compared to those without such a history. Moreover, the risk increases with the degree of genetic relatedness to an affected individual. However, relatively little is known about whether this risk for AUD – and additional psychiatric disorders – is elevated for the offspring of parents who both have AUD. To explore this association, the investigators used data from multiple nationwide Swedish registers to cover all individuals born in Sweden from 1970 to 1990 and raised in intact families. A total of 1,244,516 offspring (51.4% boys/men) were followed from 10 years of age until time of diagnosis, conclusion of the study, death, or emigration. The outcomes of interest included the time to first diagnosis of AUD, drug use disorder, ADHD, major depression, and anxiety disorder in the offspring of parents with AUD. Offspring of parents with AUD demonstrated increased hazard ratios (HRs) for AUD (HR, 2.36; 95% CI, 2.28-2.44), drug use disorder (HR, 2.04; 95% CI, 1.97-2.11), and ADHD (HR, 1.82; 95% CI, 1.74-1.90), with smaller but still elevated risks for major depression (HR, 1.43; 95% CI, 1.41-1.46) and anxiety disorder (HR, 1.43; 95% CI, 1.40-1.46). The investigators also observed that this risk was similar across parental genders. The risk for AUD was similar for the offspring of mothers (HR, 2.36; 95% CI, 2.23-2.51) and fathers (HR, 2.35; 95% CI, 2.28-2.44) with AUD. Additionally, although daughters and sons of parents with AUD displayed comparable overall outcomes, sons showed elevated HRs for major depression and anxiety disorder in comparison to daughters. Furthermore, an offspring’s risk for developing AUD was significantly higher when both parents had AUD (HR, 4.64; 95% CI, 4.26-5.05) relative to having just 1 parent with AUD (HR, 2.36; 95% CI, 2.28–2.44). The investigators concluded, “[O]ur results suggested a decomposition of the familial risk for AUD into three components: a largely nonspecific risk that included both common internalizing and externalizing disorders, a moderately specific liability to externalizing disorders, and a specific risk of AUD.” Study limitations include the reliance on diagnoses from Swedish registries – which may only detect more severe cases – and the confounding influence of parental or child comorbidity. The investigators found that the overall prevalence of disorders among the population sample was 2.72% for AUD, 3.51% for drug use disorder, 2.09% for ADHD, 15.23% for major depression, and 14.90% for anxiety disorders. Note: This article originally appeared on Psychiatry Advisor

TOPLINE: High-dose valproate is associated with weight gain in psychiatric patients, with the greatest gain reported in those taking ≥ 1300 mg/d, new data showed. METHODOLOGY: The researchers used 1-year data from two longitudinal studies conducted between 2007 and 2022. The study included 215 patients (median age, 48 years; 50% female) who had been diagnosed with bipolar disorder (38%), schizoaffective disorders (26%), schizophrenia (17%), or other conditions (16%). The researchers used linear mixed-effect models and logistic regressions to analyze the association between doses of valproate and metabolic outcomes. TAKEAWAY: Each 500-mg increase in valproate dose was associated with a weight increase of 0.52% per month over a year (P < .001), an association that was evident before and after 3 months of treatment. Weight gain was greatest for treatment durations of < 3 months (+0.56%, P < .001) compared with ≥ 3 months (+0.12%, P = .02). The greatest weight gain was observed in patients receiving doses ≥ 1300 mg/d, with a 0.50% increase in weight for each dose increment of 500 mg (P = .004). In men, each 500-mg dose was associated with an increase of 0.59%, while the trend in women was for an increase of 0.40% (P = .09). The researchers did not find associations between valproate doses and blood glucose, lipid levels, or blood pressure across a treatment period of 6 months. IN PRACTICE: "These findings underscore the need for clinicians to closely monitor patients on [valproate] for weight gain and to prescribe the lowest effective doses," the authors wrote. SOURCE: Chin B. Eap, PhD, of the Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, and the Hôpital de Cery, Prilly-Lausanne, Switzerland, was the senior and corresponding author of the study. It was published online on March 27, 2024, in the Journal of Clinical Psychiatry. LIMITATIONS: The study demonstrates an association, not causation. Treatment compliance could not be verified, although the daily dose administered to hospitalized patients was available. The study did not include information regarding lifestyle that could affect weight gain, such as dietary habits, physical activity, and substance use. DISCLOSURES: This study was funded by the Swiss National Research Foundation. Eap has received honoraria for conferences from Forum pour la formation medicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor Pharma, and Zeller in the past 3 years.

Keypoint: A digital media campaign was able to target individuals experiencing early psychosis, but did not improve treatment outcomes. A digital media campaign in New York State showed promise in identifying and engaging young individuals experiencing early psychosis online. However, the campaign did not result in significant improvements in the prompt initiation of treatment and duration of untreated psychosis (DUP), according to study results published in Schizophrenia Bulletin. Although many young people in the United States experience a first episode of psychosis (FEP), there is often a significant amount of time before individuals begin treatment. Because of the adverse health outcomes associated with prolonged DUP, researchers and health officials have increasingly explored methods to increase treatment engagement and shorten DUP. To this aim, investigators conducted a stepped-wedge randomized controlled trial (ClinicalTrials.gov Identifier: NCT03975400) to evaluate the efficacy of a digital marketing campaign aimed at reducing DUP and increasing referrals to FEP services in New York State. The campaign began in October 2020 and expanded in October 2021, targeting 6 clusters of FEP programs across New York. Each cluster underwent the intervention at varying intervals over 18 months, enabling a comparison between the intervention and control conditions before granting all sites access to the campaign. The digital campaign was advertised to target audiences who searched for relevant key terms. Once on the website, individuals were invited to take a quiz and interact with the website. The website also provided peer/clinician support and could refer individuals to mental health/social services. Participants received remote clinical assessments via text or video, identifying psychiatric symptoms and treatment history. Referral options were determined weekly based on clinical information, with suspected FEP referred to programs. The campaign also engaged individuals with suspected clinical high risk (CHR), schizophrenia spectrum disorder, or other psychotic disorders, offering referrals based on their needs. A total of 41,372 visitors accessed the website, of whom 371 proceeded to remote clinical assessment. Out of the 371 individuals assessed, 14.3% (n=53) reported symptoms aligned with psychotic spectrum disorders and these individuals were primarily girls/women (62.2%). Within the cohort of individuals with psychosis symptoms, 10.5% (n=39) showed symptoms consistent with either CHR or FEP, of which 51.3% (n=20) successfully accessed care. Most individuals suspected of CHR (n=26) or FEP (n=13) had no prior treatment (62%). Median durations of psychotic experiences were 1 to 2 years for suspected FEP and 6 months or less for suspected CHR. Among individuals who declined care (n=19), common barriers included lack of familial support, feeling unprepared for psychiatric treatment, and geographical obstacles. The campaign had no significant impact on the DUP or the number of referrals to programs for FEP participants. The DUP was similar between the control period (204.2 days) and the campaign period (196.3 days; P =.70), with no notable difference observed). Similarly, the number of program referrals and new admissions showed minimal change between the 2 periods. “This study highlights that online education and professional support alone are not sufficient to overcome help-seeking barriers and that new approaches must be developed to effectively advance the work,” the investigators concluded. Study limitations include the difficulty in assessing the COVID-19 pandemic’s influence on campaign effectiveness, the absence of comprehensive diagnostic assessments, and the potential lack of generalizability to locations outside of New York. Disclosures: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. Note: This article originally appeared on Psychiatry Advisor

Keypoint: Almost one-third of children and adolescents with ASD who report suicidal thoughts are aged 8 years and younger. Children with autism spectrum disorder (ASD) experience suicidality at a younger age than their peers without ASD, according to study results published in JAMA Pediatrics. Suicidal thoughts and behaviors were present among children with ASD who were aged 8 and younger. Individuals with ASD are at a higher risk of experiencing suicidal thoughts and behaviors. Due to the increasing prevalence of suicidality among children and adolescents in the United States more generally in recent years, investigators conducted a study to determine the age at which such suicidal thoughts and behaviors are first experienced among children with ASD. The investigators used data from the Mental Health and Suicidal Behaviors Questionnaire, a caregiver-completed online survey that was distributed by the Interactive Autism Network (IAN). The IAN is a web-based registry of approximately 28,500 children and adults with professionally-verified diagnoses of ASD. The investigators collected responses from the questionnaire from May to October 2017 and included responses from caregivers of children and adolescents with ASD aged 8 to 17 years. The current dataset comprised responses from 968 caregivers of children and adolescents diagnosed with ASD. On average, the children and adolescents were 13.4 years of age, 81.0% were boys, 19.0% were girls, and 84.8% were White. Additionally, 54.8% of the participants were on medications for emotional, behavioral, or mood-related issues. According to caregiver responses to the Mental Health and Suicidal Behaviors Questionnaire, 40.5% (n=392) of children and adolescents with ASD had expressed a wish to die, 19.3% (n=187) had wanted to end their own life, and 7.4% (n=72) had formulated a suicide plan. Among those who reported suicidality, early onset of suicidal thoughts and behaviors (at 8 years of age or younger) was noted among 36.2% of the children and adolescents expressing a wish to die, 35.3% of those who wanted to end their life, and 18.1% of respondents who had a suicide plan. Additionally, there was a single instance of a suicide attempt in a child aged 8 years or younger. The investigators noted that these results suggest a “possible earlier onset of [suicidal thoughts and behaviors] than what has been observed in typically developing youths.” Study authors concluded, “The unexpectedly high frequency of [suicidal thoughts and behaviors] among children with ASD who were 8 years or younger is particularly disturbing given the lack of validated suicide risk screening tools and interventions for this age group.” Study limitations include the reliance on parent reports that may underestimate suicidal thoughts and behaviors among offspring and the use of a survey that was not nationally representative of the population. This article originally appeared on Psychiatry Advisor

Keypoint: Among US adolescents surveyed, the prevalence of self-reported delta 8-THC use was 11.4% and the prevalence of self-reported marijuana use was 30.4% Marijuana and delta 8-tetrahydrocannabinol (THC) use is significant among adolescents in the United States, with higher THC usage in states without delta 8-THC regulations or current marijuana legalization, according to study findings published in the Journal of the American Medical Association. Investigators sought to estimate self-reported prevalence of marijuana and delta 8-THC use among adolescents in the US in the past year along with associated sociodemographic and policy factors. The investigators conducted a nationally representative cross-sectional analysis from February to June 2023, using a Monitoring the Future Study (MTF) in-school survey in which a third of the 12th grade respondents were randomly asked about delta 8-THC use. Study respondents included 2186 randomly selected 12th grade students in 27 US states. Self-reported marijuana or delta 8-THC use in the past year (any vs no use, plus the number of occasions substances were used) was the primary endpoint. In the overall analytic sample, respondents had a mean age of 17.7 years; 48.9% were women, 45.8% men, and 5.3% reported other sex or preference or declined to report; and 46.1% were White, 11.1% Black, 23.5% Hispanic, 14.2% multiracial, and 4.0% Asian. Geographically, 16.9% lived in the Northeast US census regions, 22.0% in the Midwest, 24.5% in the West, and 36.7% in the South US census regions. Overall, 34.8% lived in states with delta 8-THC regulations and 44.2% lived in states with adult-use marijuana legalization. More than half (51.7%) of respondents had a parent with a college degree. The investigators found prevalence of self-reported delta 8-THC use in the past year was 11.4% (95% CI, 8.6%-14.2%) and prevalence of self-reported marijuana use was 30.4% (95% CI, 26.5%-34.4%). Among those participants reporting delta 8-THC use (n=295), more than one-third (35.4%) used it 10 or more times in the past year. Western vs Southern census regions showed a lower prevalence of delta 8-THC use (5.0% vs 14.3%; risk difference [RD], -9.4 percentage points; 95% CI, -15.2 to -3.5 percentage points; adjusted risk ratio [aRR], 0.35; 95% CI, 0.16-0.77). Notably, these regions showed a lower prevalence of delta 8-THC use in states where delta 8-THC is regulated vs not regulated (5.7% vs 14.4%; RD, -8.6 percentage points; 95% CI, -12.9 to -4.4 percentage points; aRR, 0.42; 95% CI, 0.23-0.74) and in states with vs without legal adult-use marijuana (8.0% vs 14.0%; RD, -6.0 percentage points; 95% CI, -10.8 to -1.2 percentage points; aRR, 0.56; 95% CI, 0.35-0.91). The investigators found use in the past year for delta 8-THC was lower among Hispanic vs White youth (7.3% vs 14.4%; RD, -7.2 percentage points; 95% CI, -12.2 to -2.1 percentage points; aRR, 0.54; 95% CI, 0.34-0.87) and use in the past year for marijuana was lower among Hispanic vs White youth (24.5% vs 33.0%; RD, -8.5 percentage points; 95% CI, -14.9 to -2.1 percentage points; aRR, 0.74; 95% CI, 0.59-0.94). No difference by sex or parental education was found for delta 8-THC or marijuana use prevalence. Study limitations include the exclusion of 23 states from the survey sample as well as the exclusion of students who were absent or not enrolled in school. Also, the use of hemp-derived products was not measured. The study authors concluded, “In this nationally representative 2023 survey, 11.4% of 2186 US 12th-grade students self-reported delta 8-THC use and 30.4% self-reported marijuana use in the past year. Delta 8-THC use prevalence was higher in the South and Midwest US and in states without legal adult-use marijuana or delta 8-THC regulations.” The investigators added, “Marijuana use prevalence did not differ by cannabis policies.” This article originally appeared on Pulmonology Advisor

Keypoint: Patients treated with iloperidone had significantly larger improvements vs placebo based on the change from baseline in the Young Mania Rating Scale total score. The Food and Drug Administration (FDA) has expanded the approval of Fanapt® (iloperidone) to include the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. Fanapt is also indicated for the treatment of schizophrenia in adults. The expanded approval was based on data from a phase 3 study (ClinicalTrials.gov Identifier: NCT04819776) that evaluated the efficacy and safety of iloperidone, an atypical antipsychotic, in 414 adults with a history of bipolar I disorder who had a current episode of mania. Patients were randomly assigned 1:1 to receive either oral iloperidone (n=206) or placebo (n=208). Findings showed patients treated with iloperidone had significantly larger improvements vs placebo based on the change from baseline in the Young Mania Rating Scale (YMRS) total score at week 4 (primary endpoint; treatment difference: -4.0 [95% CI, -5.7, -2.25]; P =.000008). Significant improvements were observed as early as week 2. Secondary endpoints, including change from baseline in the Clinician Global Impression of Severity (P =.0005) and Clinician Global Impression of Change (P =.0002) scores, were also statistically significant. The safety profile of iloperidone was found to be consistent with previous trials in patients with schizophrenia. The most common adverse reactions reported were tachycardia, dizziness, dry mouth, increased alanine aminotransferase, nasal congestion, weight gain, and somnolence. “With over 100,000 patient years of experience, Fanapt is a familiar therapeutic agent that offers flexible dosing with a well-known safety profile,” said Mihael H. Polymeropoulos MD, Vanda’s President, CEO and Chairman of the Board. “This FDA approval gives patients and service providers a new treatment option for managing bipolar I disorder.” Note: This article originally appeared on MPR