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Keypoint: A third of adults with ADHD experience some form of work disability. Attention-deficit/hyperactivity disorder (ADHD) medication use is associated with a lower risk for hospitalizations – both psychiatric and nonpsychiatric – and suicidal behavior, according to study results published in JAMA Network Open. Although pharmacotherapy is the primary treatment recommendation for ADHD, there are ongoing concerns about its long-term effectiveness and safety, particularly regarding its potential effect on cardiovascular health and the risk of inducing psychosis. To this aim, researchers conducted a prospective population-based cohort study to evaluate the relationship between ADHD medication use and both hospitalization outcomes and work disability. The researchers used data from Swedish national registers to identify individuals 16 to 65 years of age who were residing in Sweden and diagnosed with ADHD between January 2006 and December 2021. The primary exposure was ADHD medication use, confirmed via Anatomical Therapeutic Chemical codes. The primary outcomes of interest included psychiatric hospitalizations, attempts of suicide or suicide-related deaths, hospitalizations for nonpsychiatric reasons, and instances of work disability (defined as instances of sickness absence lasting over 14 days or the issuance of a disability pension of any level). Both ADHD diagnoses and outcomes were verified using International Classification of Diseases (ICD) codes. A total of 221,714 individuals were included for analysis. On average, individuals were 25 years of age at baseline and 54.6% (n=120,968) were boys/men. Over half of the individuals (56.5%) presented with psychiatric comorbidities, which primarily consisted of anxiety or stress-related disorders (24%) and depression or bipolar disorders (19.5%). The majority of participants (61%) possessed a low level of education, though this was largely attributed to the group’s relatively young age. The researchers found that methylphenidate was the most commonly used ADHD medication, as it was utilized by 68.5% (n=151,837) of individuals. Lisdexamphetamine was the second most common (35.2%; n=78,106), followed by polytherapy (27.1%; n=60,102) and atomoxetine (15.6%; n=34,631). Over the 15-year study period, 25.6% (n=56,704) of individuals experienced psychiatric hospitalization. The risk for psychiatric hospitalization was significantly lower among individuals using amphetamine (adjusted hazard ratio [aHR], 0.74; 95% CI, 0.61-0.90; P =.003), lisdexamphetamine (aHR, 0.80; 95% CI, 0.78-0.82; P <.001), ADHD polytherapy (aHR, 0.85; 95% CI, 0.82-0.88; P <.001), dexamphetamine (aHR, 0.88; 95% CI, 0.83-0.94; P <.001), and methylphenidate (aHR, 0.93; 95% CI, 0.92-0.95; P <.001), relative to periods when ADHD medications were not used. The risk for suicidal behavior was also significantly lower among those using dexamphetamine (aHR, 0.69; 95% CI, 0.53-0.89; P =.004), lisdexamphetamine (aHR, 0.76; 95% CI, 0.68-0.84; P <.001), ADHD polytherapy (aHR, 0.85; 95% CI, 0.74-0.98; P =.02) and methylphenidate (aHR, 0.92; 95% CI, 0.86-0.98; P =.007). The ADHD medications associated with a lower risk for nonpsychiatric hospitalizations included amphetamine (aHR, 0.62; 95% CI, 0.45-0.84; P =.002), lisdexamphetamine (aHR, 0.64; 95% CI, 0.61-0.67; P <.001), polytherapy (aHR, 0.67; 95% CI, 0.62-0.72; P <.001), dexamphetamine (aHR, 0.72; 95% CI, 0.65-0.80; P <.001), methylphenidate (aHR, 0.80; 95% CI, 0.78-0.82; P <.001), and atomoxetine (aHR, 0.84; 95% CI, 0.78-0.90; P <.001). Additionally, the researchers evaluated work disability among a subset of 189,380 participants and found that 30% faced work disability over a 6-year follow-up period. Atomoxetine was associated with a marginally lower risk for work disability (aHR, 0.89; 95% CI, 0.82-0.97), particularly in adolescents and young adults aged 16 to 29 years (aHR, 0.82; 95% CI, 0.73-0.92). Conversely, the use of polytherapy was associated with an increased risk for work disability (aHR, 1.12; 95% CI, 1.05-1.20). “Considering the high prevalence of psychiatric comorbidity in persons with ADHD, these results suggest that ADHD medication use can reduce morbidity in adolescents and adults with ADHD,” the researchers concluded. Study limitations include limited adjustment for psychiatric conditions, incomplete clinical data due to the reliance on nationwide registers, and a lack of accurate data regarding nonpharmacological treatments, work disability (beyond the study definition), and suicide attempts that did not lead to hospital admission. Note: This article originally appeared on Psychiatry Advisor

Autism spectrum disorder (ASD) is a complex developmental condition involving persistent challenges with social communication, restricted interests, and repetitive behavior. While autism is considered a lifelong disorder, the degree of impairment in functioning because of these challenges varies between individuals with autism. Diagnosis of Autism Spectrum Disorders Early signs of this disorder can be noticed by parents/caregivers or pediatricians before a child reaches one year of age. However, symptoms typically become more consistently visible by the time a child is 2 or 3 years old. In some cases, the functional impairment related to autism may be mild and not apparent until the child starts school, after which their deficits may be pronounced when amongst their peers. Social communication deficits may include: Decreased sharing of interests with others Difficulty appreciating their own & others' emotions Aversion to maintaining eye contact Lack of proficiency with use of non-verbal gestures Stilted or scripted speech Interpreting abstract ideas literally Difficulty making friends or keeping them Restricted interests and repetitive behaviors may include: Inflexibility of behavior, extreme difficulty coping with change Being overly focused on niche subjects to the exclusion of others Expecting others to be equally interested in those subjects Difficulty tolerating changes in routine and new experiences Sensory hypersensitivity, e.g., aversion to loud noises Stereotypical movements such as hand flapping, rocking, spinning Arranging things, often toys, in a very particular manner Parent/caregiver/teacher concerns about the child's behavior should lead to a specialized evaluation by a developmental pediatrician, pediatric psychologist, child neurologist and/or a child & adolescent psychiatrist. This evaluation involves interviewing the parent/caregiver, observing, and interacting with the child in a structured manner, and sometimes conducting additional tests to rule out other disorders. In some ambiguous cases, the diagnosis of autism may be deferred, but otherwise an early diagnosis can greatly improve a child's functioning by providing the family early access to supportive resources in the community. The first step is seeking an evaluation. Most parents start with their pediatrician who is checking on developmental milestones. If your child is under the age of 3 years, you can obtain an evaluation through your local early intervention system. If your child is over the age of 3, you can get an evaluation through your local school (even if your child does not go there). Risk Factors The current science suggests that several genetic factors may increase the risk of autism in a complex manner. Having certain specific genetic conditions such as Fragile X Syndrome and Tuberous Sclerosis has been identified as conferring a particularly increased risk for being diagnosed with autism. Certain medications, such as valproic acid and thalidomide, when taken during pregnancy, have been linked with a higher risk of autism as well. (CDC) Having a sibling with autism also increases the likelihood of a child being diagnosed with autism. Parents being older at the time of pregnancy is additionally linked with greater risk of autism. Contrary to popular belief, vaccines have not been shown to increase the likelihood of an autism diagnosis, and race, ethnicity or socioeconomic status does not seem to have a link either. Male children tend to be diagnosed with autism more often than those assigned female sex at birth, albeit this ratio is changing over time. Treatment While there is no "cure" for autism, there are several effective interventions that can improve a child's functioning: Applied behavioral analysis: It involves systematic study of the child's functional challenges, which is used to create a structured behavioral plan for improving their adaptive skills and decreasing inappropriate behavior Social skills training: Done in group or individual settings, this intervention helps children with autism improve their ability to navigate social situations Speech & language therapy: It can improve the child's speech patterns and understanding of language Occupational therapy: This address adaptive skills deficits with activities of daily living, as well as problems with handwriting Parent management training: Parents learn effective ways of responding to problematic behavior and encouraging appropriate behavior in their child. Parent support groups help parents cope with the stressors of raising a child with autism Special education services: Under an Individual Education Plan provided by their school, which accommodates for their social communication deficits, restricted interests, and repetitive behaviors, children with autism can achieve their fullest potential academically. This includes special day classes for very young children to address language, social, and life skills. Treating co-occurring conditions: Children with autism experience insomnia, anxiety, and depression more often than peers without autism. They also more often have ADHD. Children with autism may have intellectual disability and this needs to be addressed. The impact of these conditions can be reduced with the proper services, which include all of the above, in addition psychotherapy and/or medication treatment Medication: A child psychiatrist can evaluate for co-morbid depression, anxiety, and impulsivity. If appropriate medications can be helpful. For example, autism-related irritability can be reduced by medications such as aripiprazole and risperidone (the two medications approved by the Food and Drug Administration for irritability associated with autism), prescribed judiciously by a knowledgeable clinician in collaboration with the child's parents. Several complementary and alternative interventions involving special diets and supplements have been tried over the years by parents/caregivers seeking ways to help their child with autism function better. To date compelling evidence has not been found to clearly recommend any such specific interventions. Research into these types of interventions continues, and parents/caregivers interested in them should discuss them with their child's treating clinician. Tips For Parents Learn as much as possible about autism spectrum disorder Provide consistent structure and routine Connect with other parents of children with autism Seek professional help for specific concerns Take time for yourself and other family members Having a child with autism affects the whole family. It can be stressful, time-consuming and expensive. Paying attention to the physical and emotional health of the whole family is important. Many national and local advocacy organizations provide information, resources and support to individuals with autism spectrum disorder and their families. A few are listed in the Resources section. Related Conditions Attention-deficit/hyperactivity disorder Social communication disorder Specific learning disorder Intellectual disability Source: American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Washington, DC: American Psychiatric Association Publishing.CDC. (2021, April 29). Autism Spectrum Disorder (ASD). Retrieved August 19, 2021, from: https://www.cdc.gov/ncbddd/autism/index.html

At a Glance Autism is a neurodevelopmental disorder that affects how people interact, communicate, and learn. Making early autism screening part of routine health care helps connect families to support and services as early as possible. Despite American Academy of Pediatrics guidelines, only a small fraction of pediatricians reported screening for autism at well-child visits. NIMH-supported efforts to close the gap between science and practice have yielded key insights into effective strategies for expanding early autism screening. Researchers are identifying new tools for detection, new models for delivering services, and new strategies for embedding early autism screening and rapid referral into routine health care. As many parents of young children know all too well, visits to the pediatrician typically involve answering a series of questions. Health care providers may ask about the child’s eating and sleeping habits or about their progress toward walking, talking, and many other developmental milestones. Increasingly, they’re also asking questions that could help identify early signs of autism. Autism is a neurodevelopmental disorder that affects how people interact, communicate, behave, and learn. It is known as a “spectrum” disorder because there is wide variation in the type and severity of symptoms people experience. Today, thanks to research focused on embedding routine screening in well-baby checkups, the early signs of autism can be identified in children as young as 12–14 months. These efforts, many supported by the National Institute of Mental Health (NIMH), show that making early autism screening part of routine health care can have a significant impact on children and families, helping connect them to support and services as early as possible. “This progress wasn’t inevitable or linear,” explains Lisa Gilotty, Ph.D., Chief of the Research Program on Autism Spectrum Disorders in the Division of Translational Research at NIMH. “Rather, it’s part of an evolving story that reflects the persistent, collective efforts of researchers and clinicians working to translate science into practice.” Identifying the disconnect The modern concept of autism as a neurodevelopmental disorder first emerged in the 1940s and coalesced into a diagnostic label by the 1980s. Diagnostic criteria evolved over time and, by the early 2000s, clinicians had evidence-based tools they could use to identify children with autism as early as 36 months. At the same time, evidence suggested that parents may notice signs even earlier, in the child’s second year of life. “Reducing this gap—between observable signs and later identification and diagnosis—became an urgent target for researchers in the field,” said Dr. Gilotty. “The research clearly showed that kids who were identified early also had earlier access to supports and services, leading to better health and well-being over the long term.” Researcher Diana Robins, Ph.D. , then a doctoral student, wondered whether an evidence-based early screening tool might help close the gap. With support from NIMH , Robins and colleagues developed the Modified Autism Checklist for Toddlers (M-CHAT) , which they introduced in 2001. They aimed to provide pediatricians with a simple screening measure that could identify children showing signs of autism as early as 24 months. The science behind early screening continued to build and gain momentum over the next few years. By the mid-2000s, researchers were exploring the possibility of using various developmental screening tools—such as the Communication and Symbolic Behavior Scales, First Year Inventory, and Ages & Stages Questionnaires—to identify early signs of autism. A young adult working on a computer gear with the text “Adults on the autism spectrum can benefit from services and supports that improve health and well-being across the lifespan.” The link points to nimh.nih.gov/autism. The growing body of evidence did not go unnoticed. In 2006, the American Academy of Pediatrics (AAP) issued evidence-based guidelines recommending autism-specific screening for all children at the 18-month visit. In a later update, they recommended adding another autism-specific screening at the 24-month visit, recognizing that some children may start showing signs a bit later in development. To the research community, these new guidelines signified a huge step forward for science-based practice. But this sense of progress was soon dashed by reality. When researchers actually surveyed health care providers, they found that very few knew about or followed the AAP guidelines. For example, in a 2006 study , 82% of pediatricians reported screening for general developmental delays, but only 8% reported screening for autism. Most of the pediatricians said they weren’t familiar with autism-specific screening tools, and many also cited a lack of time as a significant barrier to screening. The disconnect between science and practice prompted concern in the research community. A series of conversations in scientific meetings and workshops led to a crystallizing moment for the staff at NIMH. “There was a period of several years in which researchers would go off and do unfunded work and then bring it back to these meetings and say, ‘This is what I've been working on,’” said Dr. Gilotty. “It was an impetus for those of us at NIMH to say, ‘We’re going to do something about this.’” Bridging the gap Gilotty worked with colleagues Beverly Pringle, Ph.D., and Denise Juliano-Bult, M.S.W., who were part of NIMH’s Division of Services and Intervention Research (DSIR) at the time, to synthesize several file drawers’ worth of different measures, meeting notes, and research papers and distill them into an NIMH funding announcement. The announcement, issued in 2013, focused on funding for autism services research in three critical age groups: toddlers , transition-age youth , and adults . NIMH ultimately funded five 5-year research projects that specifically examined screening and services in toddlers. The projects focused on interventions that emphasized early screening and connected children to further evaluation and services within the first two years of life. In 2014, Denise Pintello, Ph.D., M.S.W., assumed the role of Chief of the Child and Adolescent Research Program in DSIR. She directed the research portfolio that included these projects, which sparked an idea: “It was such an exciting opportunity to connect these researchers because the projects were all funded together as a cluster,” she said. “I thought, ‘Let’s encourage these exceptional researchers to work closely together.’” At NIMH’s invitation, the researchers on the projects united to form the ASD Pediatric, Early Detection, Engagement, and Services (ASD PEDS) Research Network. Although the ASD PEDS researchers were using different research approaches in a range of settings, coming together as a network allowed them to share knowledge and resources, analyze data across research sites, and publish their findings together . The researchers also worked together to identify ways that their data could help address noticeable gaps in the evidence base. Building on the evidence Together, the ASD PEDS studies have screened more than 109,000 children, yielding critical insights into the most effective strategies for expanding early autism screening. For example, an ASD PEDS study led by Karen Pierce, Ph.D. , showed the effectiveness of integrating screening, evaluation, and treatment (SET) in an approach called the Get SET Early model. Working with 203 pediatricians in San Diego County, California, Pierce and colleagues devised a standardized process that the providers could use to screen toddlers for autism at their 12-, 18-, and 24-month well-child visits. The researchers also developed a digital screening platform that scored the results automatically and gave clear guidelines for deciding when to refer a child for further evaluation. These improvements boosted the rate at which providers referred children for additional evaluation and sped up the transition from screening to evaluation and services. The study also showed that autism can be identified in children as young as 12–14 months old, several years earlier than the nationwide average of 4 years. This and other studies showed that incorporating universal early screening for autism into regular health care visits was not only feasible but effective. Working closely with health care providers allowed researchers to build trust with the providers and address their concerns. “There is this sense that if you sit down and really talk with pediatricians, you can bring them into the fold,” said Dr. Gilotty. “Once you get some key people, you get a few more and a few more, and then it becomes something that ‘everybody’ is doing.” Meeting the need At the same time, the ASD PEDS studies have also explored ways to reach families with young children outside of primary care settings. Numerous studies have shown that some families are much less likely to have access to early screening and evaluation, including non-English-speaking families, families with low household incomes, and families from certain racial and ethnic minority groups. “Screening is most effective when everyone who needs it has access to it,” said Dr. Pintello. “Addressing these disparities is a critical issue in the field and NIMH’s efforts have prioritized focusing on underserved families.” One way to accomplish this is to integrate standardized universal screening into systems that are already serving these families. For example, in one study, ASD PEDS investigators Alice Carter, Ph.D. , and Radley Christopher Sheldrick, Ph.D. , worked with the Massachusetts Department of Public Health to implement an evidence-based screening procedure at three federally funded early intervention sites. The researchers developed a multi-part screening and diagnosis process that included both clinicians and caregivers as key decision-makers. They hypothesized that this standardized process would minimize procedural variations across the early intervention sites and help to reduce existing disparities in ASD screening and diagnosis. The results suggested their hunch was correct. All three study sites showed an increase in the rate of autism diagnosis with the new procedure in place, compared with other intervention sites that served similar communities. Importantly, the standardized procedure seemed to address existing disparities in screening and diagnosis. The increased rate of diagnosis observed among Spanish-speaking families was more than double the increase observed among non-Spanish-speaking families. Looking to the future Researchers are continuing to explore the best ways to put existing evidence-based screening methods into practice. At the same time, NIMH is also focused on research that seeks to develop new and improved screening tools. Evidence from neuroimaging and eye tracking studies suggests that, although the age at which observable features of autism emerge does vary, subtle signs can be detected in the first year of life. NIMH is supporting a suite of projects that aim to validate screening tools that can be used to identify signs of autism before a child’s first birthday. “In other words, are there measures we can use to identify signs even before parents and clinicians begin to notice them?” explained Dr. Gilotty. “This is the critical question because the earlier kids are identified, the earlier they can be connected with support.” These projects leverage sophisticated digital tools to detect subtle patterns in infant behavior. For example, researchers are using technology to identify patterns in what infants look at, the vocalizations they make, and how they move. They’re using technology to examine synchrony in infant–caregiver interactions. And they’re developing digital screening tools that can be administered via telehealth platforms. The hope is that new tools identified and validated in this first stage will go on to be tested in large-scale, real-world contexts, reflecting a continuous pipeline of research that goes from science to practice. “As a result of targeted research funded by NIMH over the last 10 years, we are seeing new tools for detection, new models for delivering services, and new strategies for embedding early screening and rapid referral into routine health care,” said Dr. Pintello. “I feel like it’s just the beginning of the story—we are just now seeing the impact of bringing science-based tools and practices into the hands of health care providers. Over the next few years, we hope that ongoing efforts to bridge science and practice will help us meet the unique needs of children at the exact time that they need services.” Note: This article originally appeared on NIMH

Keypoint: The device is designed to transcutaneously deliver low-level electrical stimulation to the skin behind the ears. The Food and Drug Administration (FDA) has cleared Modius Stress, a transdermal, home-use neurostimulation device that is indicated to treat the symptoms of generalized anxiety disorder in adults aged 22 and older, when used for approximately 4 weeks. The device is designed to transcutaneously deliver low-level electrical stimulation to the skin behind the ears, over the mastoid processes, through 2 self-adhesive electrode pads. The treatment is delivered for a period of 30 minutes before bed; users can engage in other activities while using the device. The prescription device includes a Modius headset, 150 electrode pads (enough for approximately 3 months use), alcohol cleansing wipes, and a micro USB charging cable. According to the Company, the clearance was granted based on data from two phase 3 trials conducted by Ulster University in the UK and Ireland and the Indian Center of Neurophysiology in India. Both were randomized, double-blind, sham-controlled trials that included patients diagnosed with generalized anxiety disorder. In the UK study, participants were instructed to use their allocated devices for 30 minutes per day for a 4-week duration at home. Results showed more patients in the Modius Stress group achieved a 4 point or more reduction in Generalized Anxiety Disorder (GAD)-7 score from the baseline visit to the week 4 visit compared with the sham group (75% [27 out of 36] vs 51% [20 out of 39], respectively). The Modius Stress group had a reduction of 5.41 in GAD-7 score vs a reduction of 3.96 in the sham group. Similar results were seen in the India study, where participants were asked to complete 20 sessions (30 minute duration) approximately 3 to 5 times per week. More participants in the Modius Stress arm achieved a 4 point or more reduction in GAD-7 score from baseline to the follow-up visit compared with the sham group (97% [33 out of 34] vs 24% [6 out of 25], respectively). The Modius Stress group had a reduction of 7.44 in GAD-7 score vs a reduction of 2.23 in the sham group (mean difference, -5.21 [95 CI, -6.57, -3.85]; P <.0001). “GAD affects an estimated 6.8 million adults in the US, over 3% of the population, with women twice as likely to be affected as men, according to the American Depression and Anxiety Association,” said Dr Jason McKeown, CEO of Neurovalens. “Modius Stress is a noninvasive device that treats the underlying issue to improve the lives of patients.” Note: This article originally appeared on MPR

Antidepressants differ in improving symptoms and preventing relapse of major depressive disorder (MDD) over a 2-year period, according to a nation-wide cohort study1 in Denmark. The study, designed to emulate a randomized controlled trial (RCT), compared long-term response of 17 antidepressants within their respective pharmacologic classes. Lars Vedel Kessing, MD, of the Copenhagen Affective Disorder Research Center, Psychiatric Center Copenhagen, and colleagues point out that clinical trials of antidepressants are commonly conducted against placebo, with few comparing active agents and fewer extending beyond short-term assessment of acute effects. They reference a comprehensive, systematic review and meta-analysis2 of 522 trials comprising 21 different antidepressants that differentiated some by acute treatment response, but point out that the need remains for comparisons by long-term effect. "Although antidepressants also reduce relapse rates, there is no consensus on which antidepressants should be preferred as a first option for long-term use," Kessing and colleagues assert. The present study, the investigators describe, "presents for the first time systematic, population-based, nationwide data on comparative 2-year long-term response within 6 antidepressant drug classes and 17 different antidepressants in patients with a first diagnosis of MDD in psychiatric hospital settings." Differentiating Antidepressants by Long-Term Response The investigators accessed Danish national health care records from between 1995 and 2018 to identify 106,920 patients treated for a first diagnosis of a single depressive episode or recurrent depressive disorder who then obtained a prescribed antidepressant. The cohort excluded patients with additional mental health disorder diagnoses and those who initially obtained multiple prescriptions, or who had antidepressants or antipsychotics prescribed 1 and 5 years prior to the index diagnosis. The antidepressants were compared within pharmacologic classes, and within each to a reference medication. Sertraline was the reference in both the selective serotonin reuptake inhibitor (SSRI) and noradrenalin reuptake inhibitor (NARI) classes, following Danish National Board of Health guidelines associating sertraline with fewer drug interactions, less association with cardiac effects, and greater safety during breast feeding. Although 8 pharmacologic classes were identified, the comparative analysis was not conducted when the sample size was less than 100. Six classes were used in the final analysis—then excluding monoamine oxidase inhibitors (MAOIs) versus sertraline, as well as bupropion versus sertraline. In addition to the SSRI and NARI, the classes were serotonin and noradrenalin reuptake inhibitors (SNRIs), venlafaxine reference, adrenergic receptor inhibitors (NaSSAs), mirtazapine reference, tricyclic antidepressants (TCAs), amitriptyline reference, and “other,” with sertraline reference. The study's primary measure was non-response, defined as switch to or add-on of another antidepressant, an antipsychotic or lithium, or inpatient hospitalization for depression. The analyses yielded estimated risk, risk difference, and relative risk (RR) of non-response for each antidepressant against the corresponding reference during a 2-year follow-up. Kessing and colleagues report that within the SSRIS, there was no statistically significant difference in absolute or relative risk difference between citalopram and the reference sertraline—but that in comparison with sertraline, there was statistically significantly higher RR of non-response with fluoxetine (1.13 [95% CI 1.10-1.17]), paroxetine (1.06, 1.01-1.10), and escitalopram (1.22, 1.18-1.25). In other analyses: Sertraline ranked higher, with less risk of non-response, than reboxetine in the NARI class. Venlafaxine ranked higher than duloxetine in the SNRI class. Mirtazapine ranked higher than mianserin in the NaSSA class. Imipramine was not statistically different from amitriptyline, which ranked higher than nortriptyline, clomipramine, and dosulepin in the TCA class. Sertraline ranked higher than agomelatine and vortioxetine in the "other" class. Contrasting Antidepressant Assessments Kessing and colleagues contrast some findings with those from a previous comparison2 of antidepressants by meta-analysis of short-term trials—typically 8 weeks—conducted by Andrea Cipriani, MD, of the Department of Psychiatry at the University of Oxford, and colleagues. Cipriani's group found, for example, no statistically significant differences in odds ratios (OR) of response between sertraline and other SSRIs, or between sertraline and reboxetine, agomelatine, or vortioxetine. There was also no statistically significant difference between the TCAs amitriptyline and clomipramine. In addition to the principal differences in these studies of short- and long-term treatment durations, Kessing and colleagues point out that their "real-world," naturalistic, register-based data minimized selection bias as well as recall bias. They also note that the meta-analysis encountered variations between clinical trials in design and cohort criteria and had relatively low statistical power available for some of the comparisons. Cipriani discussed this latest comparison of antidepressants and its focus on longer-term treatment with Psychiatric Times®. According to Cipriani, the findings that antidepressants are not all created equal for the maintenance treatment of depression and that there are differences within the same drug class, "is in line with what we found for the acute treatment of depression in our previous network meta-analyses of randomized controlled trials." Although their meta-analysis of all RCTs, including antidepressants versus placebo, revealed few differences in rates of response, subsequent analysis of only the head-to-head comparative trials did reveal diversity in range of efficacy and dropout patterns. In that analysis, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were the most effective; and fluoxetine, fluvoxamine, reboxetine, and trazadone were the least efficacious. Cipriani commented on the differences between RCTs and "real world" observations as a basis for comparing efficacy of agents. A principal distinction, he pointed out, is that RCTs apply strict inclusion and exclusion criteria and are designed primarily to assess relative effects. "Some studies have aimed to explore and quantify potential differences in drug effects between RCTs and observational real-world studies for the treatment of depression with selected antidepressants—ie, venlafaxine and duloxetine," Cipriani noted. "Differences in effect sizes between these real-world studies and RCTs were found, but it remains unclear whether they were due to differences in study populations—selected in RCTs versus unselected in real-world studies—or due to other factors. This is relevant, as lack of representativeness might impact the generalizability of RCT findings to real-world populations, particularly when there are important differences in the distribution of effect modifiers between RCT and RW patient populations." Cipriani anticipates that additional studies will help overcome the dichotomy between observational and randomized data, and appreciates that both contribute complementary information that can advance treatment. "The big challenge now is to move from estimating average effects at population level to predicting which is the best outcome for each individual patient, so we can personalize treatment and move a step forward in the field of precision psychiatry," Cipriani said. Keypoint: This article originally appeared on Psychiatric Times

Keypoint: During COVID-19, adolescents with high ACEs benefitted from in-person schooling. Among adolescents with adverse childhood experiences (ACEs), in-person schooling and coping behaviors were associated with significantly higher mental well-being during the COVID-19 pandemic, according to study results published in JAMA Network Open. Adolescent mental health has significantly deteriorated globally. With the onset of the COVID-19 pandemic, adolescents experienced disruptions to school and social routines, contributing to heightened anxiety, depression, and suicidal ideation. Mental health was particularly affected among adolescents with ACEs. However, relatively little is known about the factors which improve well-being of adversity-exposed adolescents. To this aim, researchers conducted a cross-sectional study of survey data from the Adolescent Brain Cognitive Development (ABCD) study during the COVID-19 pandemic. Adolescents 11 to 15 years of age who completed the COVID Rapid Response Research surveys of the ABCD study were included for analysis. The primary exposures were in-person schooling and 8 coping behaviors, including taking care of one’s body, exercising, engaging in healthy behaviors, neighborhood social distance activity, taking breaks from news, connecting with others online or by phone, and engaging in hobbies. Overall, 4515 adolescents were included in the analysis. On average, participants were 13.3 (SD, 0.88) years of age, 51% were girls, and 61% were White. Of the total sample, 1159 participants did not have ACEs, 3124 had 1 to 3 ACEs, and 232 experienced 4 or more ACEs. The investigators found adolescents with high ACEs had a significantly great improvement in positive affect (PA) scores with in-person schooling (B=5.55; 95% CI, 2.08-9.01) relative to adolescents with low-to-intermediate ACEs (B=1.27; 95% CI, 0.27-2.27). Additionally, in-person schooling was associated with lower perceived stress (PS) among adolescents with higher ACEs (B= -1.48; 95% CI, -2.69 to -0.28). For coping behaviors, adolescents with high ACEs benefitted from taking care of one’s body (PA: B=4.02; 95% CI, 1.39-6.66 and PS: B= -0.92; 95% CI, -1.84 to 0.00), exercising (PA: B=3.19; 95% CI, 0.46-5.92 and PS: B= -1.41; 95% CI, -2.40 to -0.43), and engaging in healthy behaviors (PA: B=4.07; 95% CI, 1.28-6.84 and PS: B= -1.01; 95% CI, -1.98 to -0.05). The researchers stated, “Among adolescents who had experienced high ACEs, in-person schooling, taking care of the body (stretching, meditating, and deep breathing), exercise, and engaging in healthy behaviors (eating healthy and sleeping well) were all associated with higher PA and lower PS scores.” Study authors concluded, “[W]e recommend that future studies build on these findings so that clinic and policy guidelines, as well as parents and educators, may identify protective factors to promote health equity and improved mental health among these adolescents at high risk of poor outcomes.” Limitations of the study include the variable timing of exploratory and outcome measures, lack of validated clinical associations for PA and PS scores, potential bias in ACE score reporting, limited generalizability due to the sample composition, insufficient power for analyzing high ACE exposure groups, and inability to investigate causal inferences due to the cross-sectional, observational design. Note: This article originally appeared on Psychiatry Advisor

People with autism spectrum disorder (ASD) face numerous healthcare disparities relative to their peers without ASD, as individuals with ASD often have reduced access to high-quality health care and experience lower satisfaction with patient-provider communication. Recent studies have begun to shed light on the unique obstetric challenges that people with ASD may experience during the perinatal period, although research on the intersectional experience of autism and pregnancy remains limited to date. “This population of childbearing people are unique in that they face multiple challenges such as unmet healthcare needs, communication issues, and experience more barriers to receiving appropriate education,” said Patricia D. Suplee PhD, RNC-OB, FAAN, associate professor at Rutgers University School of Nursing in Camden, New Jersey. Unique Challenges of Autism and Pregnancy Along with the physical, emotional, and service-related challenges that are associated with pregnancy more generally, people with ASD often experience additional perinatal difficulties compared to neurotypical individuals, according to Megan Freeth, MSc, PhD, professor of neurodevelopmental psychology and director of research and innovation in the Department of Psychology at the University of Sheffield in the United Kingdom. In a 2023 survey-based study published in the Journal of Autism and Developmental Disorders, Hampton et al compared the perinatal experiences of 384 individuals with ASD and 492 individuals without ASD. They found that those with ASD reported lower satisfaction with health care during perinatal medical encounters and were more likely to feel overwhelmed by the sensory aspects of childbirth. Although providers should avoid making assumptions about a patient’s sensory experience, Prof Freeth explained that many people with ASD can experience intense challenges with the sensory aspects of pregnancy.7 For example, they may have an extremely heightened sense of smell and taste, sensitivity to touch, or sensitivity to the lights and sounds of clinical environments. “For some, sensory experiences during birthing can result in feeling so overwhelmed that a disconnect from reality can be experienced,” she said. “Autistic people tend not to express emotional reactions in the same way as non-autistic people, and during birthing this can lead to clinical staff not realizing the severity of stress levels and can also exacerbate miscommunication, resulting in the autistic person not understanding their options and not having their preferences understood” by clinicians. Studies have also indicated that communication challenges could make it harder for individuals with ASD to ask providers for help during labor and the postpartum period. “Some autistic individuals may be unsure how to answer open-ended questions or convey how they are feeling during labor,” said Jane Donovan, PhD, RNC-MNN, assistant clinical professor at Drexel University College of Nursing and Health Professions in Philadelphia, Pennsylvania. “Additionally, during childbirth, there are numerous encounters with healthcare professionals and staff who have varying levels of experience and knowledge working with neurodiverse individuals, and these social encounters with unfamiliar people can be stressful for an autistic individual.” She noted that the stress and pain of labor can exacerbate communication differences for autistic individuals. Studies have also shown that individuals with ASD are more likely to experience postnatal depression and anxiety relative to their peers without ASD. Improving Obstetric Care and Outcomes in ASD In providing obstetric care to patients with ASD, Dr Donovan emphasized that providers need to recognize the vast diversity within this population. “It is essential to understand that autism is a spectrum condition with a great deal of variation among autistic individuals, and a provider’s view of autism should not be based on 1 patient,” she remarked. Dr Suplee offered the following recommendations for providers developing a care plan for autism and pregnancy: Assess each birthing person as an individual and do not assume that all patients with ASD will communicate or react the same way Do not make assumptions about how to provide intrapartum or postpartum care based on perceived client social interactions Learn how to interpret social cues and sensory overload and how to make appropriate accommodations to best meet the client’s needs10 Provide effective communication and tailor all education specifically to the client Discuss support services that can be incorporated during each phase of the client’s birthing journey Educate staff on what it means when a person experiences a heightened sensory perception of sound, light, or touch and what types of interventions can be utilized in these instances Prof Freeth noted, “Consistent support from the same team members throughout pregnancy is particularly valued by autistic people.” In addition, “Having clear, precise information provided in written form to supplement information provided via discussions tends to be helpful as some autistic people take a little longer than non-autistic people to process information and appreciate being able to go over key information again in their own time,” she explained. Other helpful adjustments may include options for individual or online classes or support groups — rather than large group-based formats — and allowing the presence of a patient advocate at appointments. Clinicians may need to take extra time to listen to the special concerns of these patients, especially regarding sensory issues. Providers and hospitals may also consider making small adjustments to the sensory environment, such as not having music playing or screens on in a waiting room, having the option to wait for appointments in a non-crowded space, or using a lamp for lighting instead of overhead lights, Prof Freeth recommended. Dr Donovan added that having sensory kits that contain items such as noise-canceling headphones, stress balls, sunglasses, and fidget toys available on obstetric units may help to ease sensory overload. “Implementing strategies to create a sensory-friendly environment in waiting rooms, examination areas, and on the labor and postpartum units can provide a more welcoming environment to neurodiverse individuals,” she stated. Given the high rates of comorbid mental health disorders among individuals with ASD, Dr Donovan advised that mental health screenings should be included in the plan of care for autism and pregnancy. Unmet Needs Experts point to the need for ongoing provider education and research to further understand and improve obstetric care for individuals with ASD. Ideally, such efforts would include “autistic-led training and co-production of service development whereby autistic people are involved in designing maternity services,” Prof Freeth suggested. She noted the need for research focused on the development and evaluation of such services, along with studies that would elucidate the lived experiences of pregnancy, birthing, and the postpartum period among people with ASD. Dr Donovan said she would like to see provider training programs focused on “interventions to facilitate communication and create sensory-friendly environments.” “Policies and protocols should be developed and used as guides when caring for birthing people with ASD during the intrapartum and postpartum periods,” Dr Suplee recommended. She cited the need for research exploring strategies for teaching new mothers with ASD about parenting skills and recognizing infant cues, as well as qualitative studies to “build evidence on how best to care for this population during the antepartum, intrapartum, and postpartum periods that will lead to improved maternal health outcomes.” Keypoint: This article originally appeared on Psychiatry Advisor

The ketogenic diet shows promise in reducing the symptoms of bipolar disorder and schizophrenia and reversing metabolic syndrome, results of a new pilot study show. Participants who adhered to the high-fat, low-carb diet experienced a 30% reduction in psychiatric symptoms and an average 10% reduction in weight. "We're seeing huge changes," first author Shebani Sethi, MD, of Stanford University in Stanford, California said in a press release. "Even if you're on antipsychotic drugs, we can still reverse the obesity, the metabolic syndrome, and the insulin resistance. I think that's very encouraging for patients." The findings were published online on March 27 in Psychiatric Research. Neuroprotective Effect? Recent research supports the hypothesis that psychiatric illness may stem, at least in part, from deficits in brain metabolism and that a keto diet may be neuroprotective by reducing inflammation and oxidative stress. The pilot study included 21 participants with schizophrenia (n = 5) or bipolar disorder (n = 16) who were aged 18-75 years. All were currently taking psychotropic medications. Participants were overweight (body mass index [BMI] ≥ 25) and had gained more than 5% of their body mass while taking psychotropic medication, or they had at least one metabolic abnormality, such as insulin resistance or dyslipidemia. At baseline, participants received a physical and psychiatric evaluation and 1 hour of instruction on how to implement the keto diet, which included 10% carbohydrate, 30% protein, and 60% fat. Investigators monitored blood ketone levels at least once a week and defined participants as keto-adherent if their levels were 0.5-5 mM for 80%-100% of the times they were measured. Health coaches checked in with participants for about 5-10 minutes each week to answer diet-related questions. Psychiatric assessments, which included mood rating and global functioning scales, were completed at baseline, 2 months, and at the end of the 4-month study. The research team tracked participants' adherence to the diet by weekly measurement of blood ketone levels. By the end of the trial, 14 patients had been fully adherent with the diet, six had been semi-adherent, and only one had been nonadherent. Higher ketone levels, suggesting greater adherence, correlated with better metabolic health. As measured by the Clinical Global Impression-Schizophrenia and Clinical Global Impression for Bipolar Disorder–Overall Severity, participants experienced a 31% reduction in symptom severity (P < .001). Overall, 43% (P < .02) of participants achieved recovery as defined by the Clinical Mood Monitoring Form criteria: 50% of the adherent group and 33% of those who were semi-adherent. Metabolic Benefits Initially, 29% of participants had metabolic syndrome and more than 85% had co-occurring medical conditions such as obesity, hyperlipidemia, or prediabetes. By the end of the study, none met criteria for metabolic syndrome. On average, participants experienced a 10% reduction in weight and BMI. Waist circumference was reduced by 11%, fat mass index dropped by 17%, and systolic blood pressure decreased by 6%. In addition, metabolic markers including visceral fat, inflammation, A1c, and insulin resistance also improved. All outcomes were significant at P < .001 except for systolic blood pressure, at P < .005. There was also a 20% reduction in triglycerides and a 21% increase in low-density lipoprotein cholesterol (both at P < .02). The study's limitations include its small sample size, the lack of control arm, and short duration. "Mental health and physical health are interconnected and addressing metabolic issues can complement psychiatric treatment to enhance overall well-being. Understanding the mechanisms and potential synergies between psychiatric treatment and metabolic improvements can also inform the development of more effective interventions," the researchers wrote. The study was funded by the Baszucki Group, Kuen Lau Fund, and the Obesity Treatment Foundation. The authors declare no competing interests. Note: This article originally appeared on Medscape

In this installment of Tales From the Clinic: The Art of Psychiatry, we see depression through the lens of an asylum seeker. This story is a reminder of the devastating impact of substance abuse, human trafficking, and conflict on individuals and communities. It underscores the importance of understanding the sociological aspects of drug use, including the need for structure, protection, and a sense of belonging. It highlights the critical role of trauma-informed care and policy interventions in addressing these complex challenges. This intersection between human trafficking, drug trafficking, ongoing conflict, and substance use exists in many parts of the globe. To understand this situation globally, one must consider the general principles underlying each phenomenon and leading to their confluence. In this piece, we look at the socio-economical background where the symptoms of interest developed, rather than the individual patient picture. Further, we wish to remind readers that militia, gang violence and human trafficking models share profound similarities across all countries and cultures. Case Study You see “Layla” in your outpatient clinic for depression. Her story stayed with you, as she softly cried recalling how she was able to seek asylum. Layla, a widowed mother of 2, struggled to make ends meet. The war had taken everything from her—her husband, her house, and her sense of security. They had fled and were internally displaced inside their home country of Syria. When she met “Amir,” a seemingly kind man, she felt relief. He promised to take care of her. He said that he loved her. One day, when overwhelmed by the memories of the home she had left behind, the life she once had, Amir offered her a white tablet and told her that it would help her relax. It did not take long for Layla to become dependent on it. Amir gave it to her willingly at first, then he changed. Amir told Layla that in order for him to keep giving her the tablets she had become dependent on, she needed to find other women who would work for him. Using the substance as both a lure and a means of control, Amir coerced Layla into recruiting other women. Whenever she had gone a while without using, she began to feel sick, and thought she had no other options. She complied. Layla found herself trapped in a vicious cycle of addiction and exploitation, her life spiraling out of control. One day, while wandering the streets, Layla stumbled upon a group of orphaned children. They, too, had fallen victim to the chaos, using gasoline to get high. Layla's heart ached for them, as she saw her own children reflected in their eyes. As she escaped her situation, years later, she remains depressed and bitter over her experiences, and sought care for those feelings. Substance Use Disorders and Trauma Usage Substance use, impairing an individual’s ability to function,1 can destabilize the lives of users as they experience increasing financial and social pressure to maintain and to conceal their disorder. Treatment options require a functional system for the diagnosis and treatment of users.2 Medications, therapy, and neuromodulation can be used to treat substance use disorders (SUDs). Medication assisted treatment (MAT) has been shown to be more efficacious than therapy alone.3 However, MAT requires a functional medical infrastructure for initiation of medication as well as long-term monitoring and maintenance. This medical infrastructure may be inaccessible to victims of human trafficking or patients in a zone experiencing conflict. In regions afflicted by both, those resources are effectively nonexistent. Research has shown that those who have experienced trauma are also more prone than others to SUDs. SUDs may in turn promote situations or lifestyles that are likely to result in further traumatic experiences. Many have proposed a self-medication hypothesis, suggesting that patients may utilize substances in order to ameliorate symptoms of posttraumatic stress disorder, to attempt to fall asleep better, to escape painful memories, or to reduce anxiety.4,5 For others, more stimulating medications might help to decrease feelings of anhedonia that are common after trauma, resulting in euphoria or the ability to enjoy pleasurable activities. Thus, an individual’s substance use patterns may be connected to their past traumatic experiences and ongoing substance use may make them vulnerable to an increased trauma burden and inhibit their ability to seek treatment for their SUD or a comorbid mental health disorder. Cultural and Sociological Considerations The cultural and social context of a given region greatly impacts substance users’ behavior and access to treatment. In many regions, cultural conceptions concerning substance usage affect access to care, identification of users, and adequate allocation of social resources to address these issues. In one study of individuals with SUDs, their families, and associated providers in Iran, women who used substances were more likely to be accused of engaging in sex work as a means of supporting their addiction. This stigma served as a deterrent for women seeking treatment.6 Primary care providers in Southeast Brazil were also found to negatively judge the use of tobacco, marijuana, and alcohol. Users of these same substances experience the highest rate of rejection in health care settings.7 Thus, cultural attitudes may shape barriers to care and differ across socioeconomic, geographical, and cultural contexts. Cultural conceptions surrounding substance abuse may also hinder researchers’ ability to interview individuals with a SUD, their families, or individuals in at-risk populations. These cultural barriers inhibit the ability to fully understand the scope of SUDs and, subsequently, may inhibit the ability to push for policy changes and the provision of resources to address the issue. Human Trafficking The presence of individuals who are vulnerable secondary to conflict, socioeconomic status, or legal status may predispose a region to having more trafficking activity. The intersection between human trafficking and substance abuse patterns is significant both theoretically and geographically. The overlap between forced labor and substance trafficking may be a contributing factor to the geographical overlap of drug trafficking and human trafficking routes. Human trafficking routes can also be seen in the Figure. Trafficking has several phases. In some cases, the recruitment stage is initiated by the trafficker feigning romantic interest in the victim. The trafficker may then begin to supply substances and facilitate the acquisition of these substances under certain conditions (ie, If the victim performs sex work or recruits additional victims to perform work for the trafficker). The travel-transit stage may involve confiscating documents and the initiation of violence. The exploitation phase involves the restriction of movement and poor working and living conditions as well as physical, sexual, and psychological violence. During this phase, detention or retrafficking may occur. Individuals who exit the exploitation stage without being retrafficked may reintegrate into their home country or integrate into the society of the host country.8 Understanding this framework is valuable to providers attempting to identify victims of trafficking, as victims may present for medical care at different points in this conceptual framework. Substance usage and human trafficking are intertwined as those trafficking substances may also engage in human trafficking and/or use victims as labor to support drug trafficking activities. Traffickers also often use substances as a coercion tool. Drug addiction and the threat of withdrawal may be used as a tool to coerce labor or sex.9 Victims of human trafficking may also develop SUDs as a means of coping with exploitation and trauma.10 Understanding the interactions between these phenomena may allow providers to identify more accurately patients at risk for human trafficking and increase assessment for comorbid SUDs. Groups, Conflict, and the Trafficking of Substances For organized groups, income generated from direct involvement in the sale and/or production of substances or taxation of such activities may be funneled into funding ongoing conflict via payment of combatants or acquisition of supplies.11 In Columbia, the FARC rebels funded their conflict with the government through the sale and trafficking of locally grown cocaine.12 Synthetic substances, especially, offer an opportunity for manufacturing drugs without the need for large tracts of land. As seizures of amphetamines in the Middle East reached a record high of 86 tons in 2021, double that of 2020,11 the United States sanctioned 2 relatives of a sitting president for their involvement in the production and exportation of Captagon.13 This development stresses the increasing importance of the production and trafficking of synthetic substances to fund the operations of the organized structures. The pattern of organized groups involved in conflict converting proceeds of illegal narcotic trafficking into operational funds is one which has occurred in many different regions of the globe throughout history. Increased access to substances may also serve as an incentive to fight for a given group. Historically, there is precedent for heads of armed groups giving substances to combatants to incentivize them to fight or enhance their fighting ability. Hasan-l Sabbah in the 11th century gave Hashish to his fighters, the Hashisheen, and then showed them an exquisite garden to entice them to fight for him.14 In this case, joining a fighting force provided access to substances. Drug consumption may also be used to fuel soldiers during combat. During World War II, both Allied and Axis powers distributed methamphetamines to soldiers for use as performance enhancers.15 Use of stimulants can lead to psychosis and poor judgment as well as create a dynamic in which combatants become addicted to a given substance. This may increase their reliance and allegiance to the group for which they fight. Organized groups who use trafficked substances to fund their operations contribute to the further traumatization of communities in conflict zones as violence secondary to drug trafficking further destabilizes these environments.16 Noncombatants may be lured into involvement in trafficking substances after being given the substances, as an alternative source of income after being displaced due to conflict,17 or as a coping mechanism. The illegal trafficking of substances by organized groups is a complex phenomenon which further damages communities in conflict zones. Concluding Thoughts The linkages between trauma, substance use, and human trafficking are complex and one cannot be fully understood in isolation from another. Practical implications for approaching the confluence of these issues should be considered by providers and regulators. Local health workers should be trained in trauma informed care due to the widespread political and economic instability. Policy changes should consider the interplay between trauma, substance use, and human trafficking. Providers should consider the overlapping phenomena which may lead to a patient using substances, having a trauma history, and experiencing trafficking. Overall, those seeking to tackle these issues and treat patients like Layla need to be cognizant of the economic, social, and cultural environment which shape patient’s experiences and interfere with their treatment and recovery.

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: 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