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Keypoint: About 6% of individuals with a suicide attempt have never been diagnosed with a psychiatric disorder. Approximately 20% of adults with lifetime suicide attempts did not meet the criteria for a psychiatric disorder diagnosis before their first attempt, according to new research published in JAMA Psychiatry. Although suicidality is commonly associated with pre-existing psychiatric disorders or distress, not all individuals who die by suicide have an antecedent psychiatric disorder. The current study sought to explore lifetime suicide attempts among psychiatrically healthy individuals by investigating the prevalence of lifetime suicide attempts in healthy volunteers, examining the timing of such attempts relative to the onset of psychiatric conditions, and comparing rates across different demographics. Researchers leveraged data for this cross-sectional study from the National Epidemiologic Study of Addictions and Related Conditions III (NESARC-III), which assessed diagnoses from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and surveyed respondents on suicidal behavior. Among those reporting a lifetime suicide attempt, the researchers calculated attempt frequencies for both healthy volunteers and persons with lifetime psychiatric disorders. Of the 36,309 NESARC-III respondents, 66.8% (95% CI, 64.1%-69.4%) were women and 1948 (5.2%; 95% CI, 4.8%-5.6%) reported lifetime suicide attempts. For those with a history of suicide attempts, 128 (6.2%; 95% CI, 4.9%-7.4%) were healthy volunteers without a prior psychiatric diagnosis and 261 (13.4%; 95% CI, 11.6%-15.2%) made a first suicide attempt before the onset of a psychiatric disorder. As such, an estimated 19.6% of respondents reported a lifetime suicide attempt with no evidence of a psychiatric disorder prior to their attempt. While women were approximately twice as likely as men to report a lifetime suicide attempt (P <.001), the percentage of individuals with lifetime suicide attempts who were healthy volunteers or lacked a psychiatric disorder prior to attempts did not significantly vary by sex. However, women were significantly more likely than men to make a suicide attempt in the same year as the onset of a psychiatric disorder (P <.001), while men were more likely to experience an attempt following the onset of a psychiatric disorder (P <.001). These study findings indicate that an estimated 6.2% of individuals in the United States who attempted suicide were healthy volunteers, and this percentage increased to 19.6% when including those whose suicide attempts occurred before the onset of a psychiatric disorder diagnosis. Study authors concluded, “This finding challenges clinical notions of who is at risk for suicidal behavior and raises questions about the safety of limiting suicide risk screening to psychiatric populations.” Study limitations include the reliance on self-reported information and a lack of data on psychiatric diagnoses that were not assessed in the NESARC-III survey. Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of author disclosures. This article originally appeared on Psychiatry Advisor

Keypoint: A daily 60-mg dose of atogepant significantly reduced mean monthly migraine days in patients with episodic migraine. A daily 60-mg dose of atogepant taken over the course of 12 weeks reduced mean monthly migraine days in adult patients with episodic migraine who failed 2-4 classes conventional treatments, according to study results published in The Lancet Neurology. Researchers conducted a randomized, double-blind, placebo-controlled, phase 3b trial (ELEVATE; ClinicalTrials.gov identifier: NCT04740827) to evaluate the safety, tolerability, and efficacy of daily atogepant in adult patients with episodic migraine who did not respond to 2-4 classes of conventional oral preventative treatments. The primary outcome of interest was change from baseline in mean monthly migraine days across the 12-week treatment period. Secondary outcomes included change from baseline in mean monthly headache days and medication use across the same treatment period. Both the primary and secondary endpoints were analyzed using a mixed model for repeated measures. Adult patients were eligible for the study if they had a history of migraine for at least 1 year and migraine onset prior to age 50. Patients included in the study also had 4-14 monthly migraine days and documented failures by 2-4 classes of oral migraine preventative treatments, 1 of which was propranolol or metoprolol, topiramate, flunarizine, or amitriptyline. Between March 2021 and August 2022, patients (N=315; 89% women; 96% White) were randomly assigned 1:1 to receive either 60 mg of oral atogepant (n=157) or placebo (n=158) daily during the treatment period. Of these 315 patients, 313 received treatment (atogepant, 156 vs placebo, 157) and were included in the safety population. The most common previous preventative treatment failures were topiramate (55%) and amitriptyline (53%). Most patients had been failed by 2 classes of treatment (56%), followed by those who had been failed by 3 (35%), and finally those who had been failed by 4 (9%). Compared with placebo, atogepant significantly reduced the mean monthly migraine days across the treatment period. The least squares mean changes from baseline in mean monthly migraine days across the treatment period was -1.9 (standard error [SE], 0.4) with placebo vs -4.2 (SE, 0.4) with atogepant. The least squares mean difference from placebo was -2.4 days with atogepant (95% CI, -3.2 to -1.5; adjusted P <.0001). Atogepant also demonstrated more significant improvements for all secondary efficacy endpoints. In the atogepant group, 78 (51%) patients had a reduction of at least 50% in mean monthly migraine days over the treatment period vs 28 (18%) patients in the placebo group (odds ratio [OR], 4.8; 95% CI, 2.9-8.1; adjusted P <.0001). The least squares mean difference for change from baseline in mean monthly headache days was -2.2 (95% CI, -3.1 to -1.3; adjusted P <.0001), indicating the superior performance of atogepant. Similarly, the least squares mean difference for change from baseline in mean monthly acute medication use days was-2.6 (95% CI, -3.4 to -1.9; adjusted P <.0001), again favoring atogepant. Treatment-emergent adverse events (TEAEs) were reported by 81 (52%) patients in the atogepant group vs 84 (54%) patients in the placebo group. Constipation, COVID-19, nausea, and nasopharyngitis were the most commonly reported TEAEs across both the placebo and atogepant groups (3% vs 10%; 10% vs 8%; 3% vs 7%; 8% vs 5%, respectively). Most TEAEs were mildly or moderately severe. Study limitations included a relatively brief treatment period, as well as the exclusion of patients who had been failed by more than 4 treatment classes and those with chronic migraine. “Future studies should consider examining the efficacy, tolerability, and safety of atogepant in patients with chronic migraine and for whom two to four previous preventive treatment classes have failed,” the researchers concluded. Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and or/device companies. Please see the original reference for a full list of disclosures. This article originally appeared on Neurology Advisor

Keypoint: Treatment with 2 doses of CYB003 led to robust and sustained improvements in depression symptoms at 4 months. The Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to CYB003, a proprietary deuterated psilocybin analog for the adjunctive treatment of major depressive disorder (MDD). The designation was based on data from a phase 2 trial (ClinicalTrials.gov Identifier: NCT05385783) that evaluated the psychedelic-based therapeutic in patients with moderate to severe MDD. Findings showed treatment with 2 doses of CYB003 (12 mg or 16 mg) led to robust and sustained improvements in depression symptoms at 4 months. In both dosing cohorts, the mean reduction from baseline in the Montgomery–Asberg Depression Rating Scale (MADRS) score was approximately 22 points from baseline. In the 16 mg group, roughly 75% of patients were considered responders, defined as at least a 50% improvement in MADRS score, after 2 doses. Remission rates (defined as MADRS score ≤ 10) were reported to be 60% and 75% in the 12 mg and 16 mg cohorts, respectively, following 2 doses. “The sustained reduction in depression symptoms at the four-month mark after just 2 doses of CYB003 is a critical milestone that demonstrates the durability of the response, following the rapid improvement in symptoms,” said Amir Inamdar, MBBS, DNB (Psych), MFPM, Chief Medical Officer of Cybin. “Unlike currently approved adjunctive treatments which require chronic, daily dosing, CYB003 allows for intermittent dosing without the challenges of withdrawing patients from their existing medications.” With regard to safety, no drug-related serious adverse events were reported in the study. Suicidal ideation or behavior were not observed during the trial period. “Considering these positive findings, we are eager to progress the program and bring relief and treatment alternatives to the millions of people who can benefit,” added Inamdar. The Company stated that a phase 3 trial is expected to begin in mid-2024. This article originally appeared on MPR

Keypoint: Psilocybin poisoning exposures started to significantly increase starting in 2019 for adolescents and in 2020 for adults. From 2018 to 2022, psilocybin poisoning calls have tripled for adolescents and doubled for young adults, as reported in the Journal of Adolescent Health. The psychoactive agent in hallucinogenic mushrooms, psilocybin, can cause intense psychedelic hallucinations, euphoria, and altered perception of space and time. Although psilocybin is designated as a Schedule I substance in the US, multiple cities and states have taken steps to decriminalize psilocybin. To evaluate trends in adolescent and young adult exposures to psilocybin in the US, investigators from the University of Virginia School of Medicine sourced data for this study from the National Poison Data System (NPDS). The investigators identified cases between 2013 and 2022 in which individuals (N=4055) aged 13 to 25 years were exposed to psilocybin. The investigators also collected the available demographic data, level of healthcare received, reason for exposure, and medical outcome. Among reported psilocybin exposures, 2372 cases involved adolescents and 1683 involved young adults. Most psilocybin poisoning calls involved boys or men (74.8% to 75.1%), most events involved intentional abuse (78.3% to 81.1%), and 65.8% were single-substance exposure events. The number of psilocybin-related cases was relatively stable between 2013 and 2018. However, the number of cases started to significantly increase starting in 2019 for adolescents and in 2020 for adults (both P <.001). By 2022, cases had more than tripled among adolescents (P <.0001) and more than doubled among young adults (P <.0001) compared with 2018. From 2013 to 2022, the number of cases more than doubled among men and boys (246 to 545; P <.0001) and almost tripled among women and girls (73 to 213; P <.0001). In single substance cases, 72.3% of adolescents and 72.1% of adults received medical attention and the event resulted in a moderate effect on 47.1% of adolescents and 45.3% of adults. The most common effects included hallucinations or delusions (36.6%), agitation (27.6%), tachycardia (20.2%), and confusion (16.0%). In addition, seizures were reported in 1.8% of cases. In multiple exposure cases, the most common co-occurring substances were marijuana among adolescents and alcohol among adults. Two deaths occurred in cases that involved fentanyl and hallucinogenic amphetamine, in which psilocybin was determined to be the secondary cause of death in both cases. These findings indicate that psilocybin poisoning exposures have significantly increased in recent years among adolescents and young adults in the US. Study authors concluded, “As psilocybin might become more available, continued surveillance is critical to inform lawmakers and guide public policy.” The primary limitation of this study is that reporting to poison control is voluntary and only includes cases that rise to the level requiring medical attention, so rates of psilocybin use in this study are likely an under-representation of real-world use. Note: This article originally appeared on Psychiatry Advisor

Adverse childhood experiences (ACEs) are associated with a significantly increased risk for adult depressive, anxiety, and stress-related disorders, new data from a large registry study of twins showed. Researchers found that each additional adverse event placed children at a 52% greater risk for a psychiatric disorder as an adult, with sexual abuse associated with the greatest risk. The findings showed that the association held even after controlling for shared genetic and environmental factors. The results suggested that "interventions targeting ACEs, including primary prevention and enhanced access to evidence-based trauma therapies to individuals who experienced ACEs, may be associated with reduced risk of future psychopathology," the investigators, with first author Hilda Björk Daníelsdóttir, MSc, of the University of Iceland, Reykjavik, Iceland, wrote. The findings were published online on March 6 in JAMA Psychiatry. Dose-Dependent Effect Previous research has shown a robust link between childhood abuse and an increased risk for psychiatric disorders in adulthood, but evidence of this association in studies that adjust for familial confounding is "completely lacking," the investigators wrote. To learn more about how genetic factors may affect the relationship between ACEs and later psychiatric diagnoses, the investigators used data from the nationwide Swedish Twin Registry, which includes data on more than 25,000 identical and nonidentical twins. The twin registry is linked to the Swedish National Patient Registry, which includes information on inpatient or outpatient psychiatric diagnoses after age 19. The twins responded to a large web-based questionnaire about past-week depressive symptoms as a measure of current mental health and distinct types of ACEs including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime. Three birth cohorts from the twin registry were surveyed between 2005 and 2016 and followed up in the national registry from age 19 until the end of 2016. Among the sample of 25,000 twin pairs (15,000 female; mean age at assessment, 29 years), 9750 (39%) participants reported exposure to at least one ACE, while 2000 (8%) reported exposure to three or more ACEs. Most respondents — 61% — reported no ACE exposure. More than 2300 participants received a psychiatric diagnosis as an adult. The incidence of any psychiatric disorder increased from 503 individuals (6.4%) among participants without any ACEs to 993 individuals (24.6%) among those reporting three or more. At the cohort level, a greater number of ACEs was associated with increased odds of any psychiatric disorder in a dose-dependent manner, the investigators noted (odds ratio [OR], 1.52; 95% CI, 1.48-1.57). Untangling Genes and Environment To determine how much of the increased risk for adult mental illness is due to ACEs and how much can be attributed to genetics and environment, the researchers focused on twin pairs where one had exposure to one type of ACEs and the other did not. This analysis revealed that the association remained but was attenuated. In identical twins, the effect of each ACE raised the odds of having a psychiatric condition by 20% (1.20; 95% CI, 1.02-1.40), and for nonidentical twins, the odds increased by 29% (1.29; 95% CI, 1.14-1.47). The weakening of the risk "suggests that familial confounding contributed to the association between ACEs and adult mental health outcomes," the authors wrote. Of all the ACEs, sexual abuse carried the highest risk for adult psychiatric disorders. Children who were exposed to sexual abuse, compared with those who were not, had up to a 200% higher risk for any psychiatric disorder in the following comparisons: Full cohort (OR, 3.09; 95% CI, 2.68-3.56), dizygotic twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and monozygotic twin pairs (1.80; 95% CI, 1.04-3.11). "Our results demonstrated that familial factors contributed to a lesser extent to the association between sexual abuse and adult psychiatric disorders," the authors wrote. One major limitation of the study was that ACEs were based on retrospective report and thus may be subject to recall bias. Also, the findings cannot be generalized to other countries or cultures. The study was funded by the European Research Council, the Icelandic Center for Research, and the European Union Horizon 2020. Disclosures are noted in the original article. Note: This article originally appeared on Medscape

Keypoint: A reduced risk was seen for venous thromboembolism, arterial thrombosis/thromboembolism, and heart failure. HealthDay News — COVID-19 vaccination is associated with a reduced risk for post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cardiac and thromboembolic outcomes, according to a study published online March 12 in Heart. Núria Mercadé-Besora, from the University of Oxford, and colleagues conducted a staggered cohort study based on national vaccination campaigns using electronic health records from the United Kingdom, Spain, and Estonia to examine the association between COVID-19 vaccination and the risk for post-COVID-19 cardiac and thromboembolic complications. Outcomes included heart failure, venous thromboembolism (VTE), and arterial thrombosis/thromboembolism (ATE) recorded at 0 to 30, 31 to 90, 91 to 180, and 181 to 365 days after SARS-CoV-2 infection. The analyses included 10.17 million vaccinated and 10.39 million unvaccinated individuals. The researchers found that vaccination was associated with reduced risks for acute and postacute COVID-19 VTE, ATE, and heart failure, with meta-analytic subhazard ratios of 0.22, 0.53, and 0.45 and 0.53, 0.72, and 0.61 for 0 to 30 days and 91 to 180 days after SARS-CoV-2 infection, respectively. “Vaccination against SARS-CoV-2 substantially reduced the risk of acute post-COVID-19 thromboembolic and cardiac complications, probably through a reduction in the risk of SARS-CoV-2 infection and the severity of COVID-19 disease due to vaccine-induced immunity,” the authors write. Note: This article originally appeared on Psychiatry Advisor

COMMENTARY The diagnosis of attention-deficit/hyperactivity disorder (ADHD) continues to be the focus of controversy in psychiatric literature.1 I would like to begin by critically examining the “H” in “hyperactivity,” as suggested by S. Nassir Ghaemi, MD. I concur with Dr Ghaemi that distractibility and “hyperactivity” are not part of the same psychological problem. Since 1991, when I started to observe the behaviors of children diagnosed with ADHD, I have noticed that “hyperactivity” is associated with either a mood disease or anxiety.I have hundreds of cases documented in 3 books,3-5 and as of today, I have not found 1 case in which the increased activity, physical or psychological, is associated with a diagnosis of ADHD. On the contrary, the reported “hyperactivity” has been a manifestation of obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), social anxiety, bipolar illness, autism, and a few other diseases. On the other hand, as my mentor and friend Ronald W. Pies, MD, likes to say, “the body can have as many illnesses as it pleases.”6 The key difference between having several concurrent diseases and an unjustified diagnosis is that in the first scenario, every medical entity has symptoms of its own. The following vignette is an example of a frequently encountered diagnostic confusion. Case Example “Kevin” is a preadolescent Caucasian boy raised by his grandmother. From early childhood, he was exposed to physical neglect, and he also witnessed the assassination of his father, who was described as a violent person and addicted to street drugs. While in foster care, Kevin was sexually molested and again suffered emotional and physical neglect. He has severe anger issues, but his grandmother says he is very smart and can do his schoolwork, if he wants to. Several psychiatrists and psychotherapists have diagnosed him with PTSD, bipolar disorder, autism, bulimia, and insomnia. Lastly, a school counselor had Kevin and his grandmother complete a Vanderbilt questionnaire and determined that Kevin has ADHD. Discussion It seems obvious that a person like Kevin would have impaired attention in the classroom, but the questionable habit of elevating symptoms to the status of a diagnostic category misled the school clinician to diagnose ADHD, leading to other serious consequences from giving psychostimulants to a child misdiagnosed with ADHD, but suffering from mood and/or anxiety disorders. I should emphasize that Kay Redfield-Jamison, PhD, said once in an interview, “There are few things worse than putting a child with bipolar illness on stimulants.”7 And then, there is what I would call institutional fallacy. Here is 1 example: Six respected researchers from a prestigious university published their findings in an esteemed psychiatric journal.8 The writing is impeccable, and the conclusions appear to be sound, but when you read between the lines, something is not right. In the first paragraph, they say, “For example, in a study of robust open-label dosing with lisdexamfetamine, 40% of adults with ADHD were considered to have unresolved and clinically significant impairment in essential elements of executive behavior. Therefore, there is a significant need for new ADHD interventions.” Notice that the investigators assume that all the participants in the study quoted by them have ADHD. Furthermore, how can a drug weaker than lisdexamfetamine (Vyvanse) have a significant effect on an individual with an impaired attention span when conventional amphetamines failed to improve symptoms? If you wonder why I question the accuracy of the diagnosis in that study,9 I must say that I do so in any ADHD publication, and I have an abundance of evidence to sustain my view (see references). However, the investigators of this second study are heavyweights in the field who I respect and admire. Over several decades, I have encountered thousands of children (and adults with a childhood history) who were labeled conduct disorder and/or oppositional-defiant plus ADHD, when in fact they had OCD, social anxiety, PTSD, bipolar disorder, or even schizophrenia. It may be hard to believe, but I treated 2 children who for several years were receiving methylphenidate while having constant auditory hallucinations. Not surprisingly, they were adopted by nice families, and the evaluating physicians assumed that the legal guardian in front of them was the child’s birth mother. Another component of “institutional fallacy” is the pervasive belief that ADHD is a frequent comorbidity with other diagnoses. If we agree that ADHD is a diagnosis of exclusion, we then need to ask for the science behind the validity of those co-occurrent illnesses. As Dr Ghaemi and the late professor Hagop Akiskal, MD,10 stated multiple times, we should diagnose ADHD only when other explanations for an impaired attention span have been ruled out. I propose that we reclaim science and discard false assumptions, including that sleep disruption, moodiness, aggressive or defiant behaviors, autistic obsessions, etc, are inherent components of the ADHD syndrome. Instead, we should be digging deeper to determine if non-ADHD disorders better explain these features. Note: This article originally appeared on Psychiatry Times

HealthDay News — Primary care pediatricians feel less prepared to manage adolescents’ opioid use disorder (OUD) compared with other substances, according to a research letter published online Feb. 26 in JAMA Pediatrics. Scott E. Hadland, M.D., from Mass General for Children in Boston, and colleagues used data from 474 primary care pediatricians participating in the 2021 American Academy of Pediatrics Periodic Survey to assess their preparedness to provide adolescent OUD care. The researchers found that most agreed or strongly agreed that it is their responsibility to identify substance use disorders (93.9 percent) and refer patients to treatment (97.4 percent). However, fewer participants agreed or strongly agreed that it is their responsibility to treat substance use disorders (20.3 percent) or prescribe medications for addiction treatment (12.4 percent). Fewer respondents felt prepared or very prepared to counsel adolescents on opioid use (48.3 percent) with compared with alcohol (87.1 percent), cannabis (81.7 percent), and electronic cigarette use (80.1 percent). Compared with other substances, pediatricians were less likely to provide counseling (63.0 percent) and more likely to refer patients off-site for care (71.8 percent) for opioid use compared to alcohol (87.7 and 51.7 percent, respectively), cannabis (88.9 and 45.4 percent, respectively), and e-cigarette use (91.6 and 26.5 percent, respectively). Less than one-quarter of respondents (23.7 percent) reported ever diagnosing an adolescent with OUD, and only 5.5 percent had ever prescribed OUD medication. “With the growing problem of OUD, training on OUD management in primary care is needed,” the authors write.

Keypoint: Antidepressant dispensing to adolescent girls rose by 129.6% during the pandemic, relative to pre-pandemic levels. Antidepressant dispensing to adolescents and young adults increased by 63.5% during the COVID-19 pandemic, relative to pre-pandemic levels. This increase was largely driven by increased antidepressant dispensing to girls and women, according to study results published in Pediatrics. Although a wealth of evidence indicates that the COVID-19 pandemic was detrimental to mental health — particularly among adolescents — relatively little is known about the temporal changes in antidepressant dispensing rates during this period. To determine whether antidepressant dispensing patterns changed during the pandemic, researchers used the IQVIA Longitudinal Prescription Database, a comprehensive all-payer national database, to track the distribution of antidepressant prescriptions from 2016 to 2022 among US individuals aged 12 to 25 years. The researchers categorized individuals into 2 groups: adolescents (12 to 17 years of age) and young adults (18 to 25 years of age). The primary measure was the rate of antidepressant prescriptions dispensed monthly, calculated as the number of adolescents and young adults receiving at least 1 antidepressant prescription per 100,000 people aged 12 to 25 years. The researchers evaluated both slope and level changes in prescription rates and examined variations by sex and age group. Between 2016 and 2022, a total of 221,268,402 antidepressant prescriptions were dispensed to 18,395,915 individuals from the database. On average, individuals were 19.2 (SD, 3.9) years of age at the time of sample entry and 64.4% were girls/women. Geographically, 38.6% of individuals resided in the South, 25.7% in the Midwest, 19.6% in the West, and 16.1% in the Northeast. Of the total dispensed antidepressant prescriptions, 67.3% were for selective serotonin reuptake inhibitors (SSRIs), and the 3 most common medications were sertraline (24.1%), fluoxetine (18.5%), and escitalopram (16.3%). From 2016 to 2022, there was a 46.1% increase in the number of adolescents and young adults receiving at least 1 dispensed antidepressant prescription, and the rate of new initiations to antidepressant therapy grew by 31.0%. The monthly antidepressant dispensing rates increased by 66.3% from January 2016 to December 2022. Prior to March 2020, the monthly dispensing rate was rising at 17.0 (95% CI, 15.2-18.8) individuals per 100,000 per month. While the onset of the COVID-19 pandemic did not lead to an immediate level change in the dispensing rate (-37.4; 95% CI, -153.4 to 78.7), it was linked to an increase in the growth rate to 10.8 (95% CI, 4.9-16.7) per month. After March 2020, the monthly rate of antidepressant dispensing escalated to 27.8 per month (95% CI, 22.1-33.4), representing a 63.5% increase compared with the rate of change before March 2020. This increase in monthly antidepressant dispensing rates was largely driven by increased antidepressant dispensing to girls and women. Among adolescent girls, the monthly dispensing rate surged by 41.1 (95% CI, 32.9-49.2), a 129.6% increase from the pre-pandemic rate. Young adult women also experienced a 56.6% increase from the pre-pandemic levels, as the dispensing rate rose by 44.8 (95% CI, 33.3-56.3) per month. In contrast, the pandemic caused a level decrease (-224.3; 95% CI, -328.2 to -120.4) and no significant slope change (1.1 per month; 95% CI, -2.3-4.4) among adolescent boys. Young adult men also did not experience significant level (17.8; 95% CI, -51.3-86.8) or slope changes (3.7 per month; 95% CI, -0.8-8.2) after March 2020. Study authors concluded, “Using 2016 to 2022 data from a national prescription dispensing database, we found that antidepressant dispensing to adolescents and young adults rose 63.5% faster after the COVID-19 pandemic. This change was driven by increased antidepressant dispensing to female patients.” Study limitations include the lack of data for prescription indications and the modality of prescription encounters (in-person vs telehealth). Note: This article originally appeared on Psychiatry Advisor

Several morbidities, including bipolar disorder, dementia, and vitamin D deficiency, were associated with an increased risk for serious infection among patients with rheumatoid arthritis (RA), according to study results published in Seminars in Arthritis & Rheumatism. It is important to understand the significant factors contributing to the risk for serious infection and to what extent these risks can be reduced, especially in patients with RA. However, no prior studies have examined the association between serious infection risk and a comprehensive list of morbidities. To determine this association, researchers conducted a retrospective, observational, population-based cohort study that included adult patients with RA living in 8 counties within Minnesota. Patients were followed-up until death, migration, or until December 31, 2021. A total of 55 comorbidities were identified using medical records and selected based on their prevalence among the specific patient population. The relationship between each morbidity and the risk for serious infection was evaluated using 3 different conditional frailty models. Serious infections included those that required hospitalization for at least 1 day. A total of 911 individuals with RA were included in the analysis, 70% of whom were women with a mean age of 56 years. Overall, 293 serious infections were reported among 155 individuals, corresponding to an infection incidence of 3.9 per 100 person-years. More than half of the participants had multiple comorbidities, the most common of which were osteoarthritis (55.2%), hyperlipidemia (54.6%), hypertension (53.6%), and chronic back pain (53.1%). Serious infections were most frequently reported in the lower respiratory tract (35.5%), the bloodstream/sepsis (28.3%), the skin and soft tissue (14.0%), and the intestines (10.9%). The risk for serious infection in each of the 55 morbidities was adjusted for age, sex, and calendar year in the first model; 27 morbidities were linked to an increased risk for serious infection. Bipolar disorder was associated with the greatest risk for serious infection, with a hazard ratio (HR) of 4.73 (95% CI, 1.57-14.21). With each additional morbidity, the risk for serious infection was increased by an average of 16%. The second and third models adjusted for Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) and Mayo serious infection risk scores, in addition to age, sex, and calendar year. Upon accounting for RABBIT risk scores, 11 of the 55 morbidities were linked to a significantly increased risk for serious infection, while 23 morbidities were associated with an increased risk after accounting for Mayo scores. Bipolar disorder maintained a marked risk association, emerging as the morbidity with the second-highest serious infection risk, following adjustment for RABBIT scores (HR, 6.23; 95% CI, 2.11-18.41). Bipolar disorder was associated with the greatest risk after adjusting for Mayo scores (HR, 5.24; 95% CI, 2.34-11.73), according to the second and third models. Additional morbidities that repeatedly ranked within the top 10 for effect size in all 3 adjustment models included dementia, vitamin D deficiency, and sleep apnea. Furthermore, patients with anemia, chronic kidney disease, chronic skin ulcers, hematologic cancers, post-traumatic stress disorder, liver disease, and leukopenia faced a 2-fold greater risk for serious infection in all 3 models. Study results were limited by the retrospective and observational nature. Additionally, the use of medical codes to identify morbidities has inherent weaknesses. Moreover, the number of observations that the RABBIT and Mayo risk models could adjust for was limited due to missing data. Study authors concluded, “Additional studies in other populations are needed to confirm the association between [serious infection] risk and morbidities included in this study, especially morbidities that do not have a clear biologic basis for increasing infection risk.” This article originally appeared on Rheumatology Advisor

HealthDay News — Exercise is an effective treatment for depression, especially when intense, according to a review published online Feb. 14 in The BMJ. Michael Noetel, Ph.D., from the University of Queensland in St. Lucia, Australia, and colleagues conducted a systematic review and network meta-analysis to identify the optimal dose and modality of exercise for treating major depressive disorder. A total of 218 unique studies with 495 arms and 14,170 participants were included. The researchers found moderate reductions in depression for walking or jogging, yoga, strength training, mixed aerobic exercises, and tai chi or qigong compared with active controls (e.g., usual care, placebo tablet; (Hedges’ g, −0.62, −0.55, −0.49, −0.43, and −0.42, respectively). The impact of exercise was proportional to the intensity. The most acceptable modalities seemed to be strength training and yoga. The results were robust to publication bias; only one study met the Cochrane criteria for a low risk for bias. Confidence in the network meta-analysis was considered low for walking and jogging and very low for other modalities. “Our findings support the inclusion of exercise as part of clinical practice guidelines for depression, particularly vigorous intensity exercise,” the authors write. “Doing so may help bridge the gap in treatment coverage by increasing the range of first-line options for patients and health systems.”

This story is part of a special 75th Anniversary series featuring the experiences of people living with mental illnesses. The opinions of the interviewees are their own and do not reflect the opinions of NIMH, NIH, HHS, or the federal government. This content may not be reused without permission. Please see NIMH’s copyright policy for more information. Note: This feature article contains information and depictions of schizoaffective disorder (a mental illness characterized by symptoms similar to those of schizophrenia). If you or someone you know has a mental illness, is struggling emotionally, or has concerns about their mental health, there are ways to get help. If you are in crisis, call or text 988 to connect with the 988 Suicide Crisis Lifeline . To learn more about this disorder, visit NIMH’s schizophrenia health information page. Everything about Ray Lay exudes positivity. He’s friendly, outgoing, and a role model. But behind his gray beard and warm smile, there’s a story: part tragedy, part hope and redemption. Once a happy kid who used to help his father fix cars, everything changed on a fateful road trip in 1960. The changes Five-year-old Lay and his family were on a cross-country drive in Mississippi when they got into a car accident. “The next thing I remember, I came to, and I’m looking down on the windshield. I’m seeing the blood, and I passed out again,” Lay said. “I woke up, and I’m in a man’s lap, in the ambulance.” Slipping into a coma, Lay awoke 3 weeks later with more than 300 stitches. Once back in the schoolyard, his peers teased him. “When I went to school, the kids—mean kids,” he recalled, “they used to call me Scarface.” Lay didn’t know it then, but other changes were underway. He had begun talking to people who weren’t there. The first of these was Mel. “When I woke up … after I went through the windshield, I saw my guardian angel, Mel,” Lay said. “He had white hair, white beard, dressed in all white, and as he would open his robe, he had snakes or worms in his chest. And I remember that part like it was yesterday. That was when he told me who he was and that he was there to protect me.” To Lay, Mel was as real as a parent or teacher. And when he told Lay to do things, Lay listened. At Mel’s urging, Lay began fighting the school bullies. Then, other kids. The rapid changes in his behavior left his father mystified. “My daddy said I was the sweetest little boy,” Lay recalled. “And then, when I went through that windshield, he said, it was like the devil got in me.” Childhood lost At 7, Lay was expelled and shuffled to another school, where he routinely skipped class. By 8, authorities had sent him to a state juvenile detention center. “I can’t say I was conflicted because, more likely than not, I probably didn’t even understand what that meant,” Lay said. “As far as the right or wrong, all the right was what Mel said to do.” While they disciplined him often, Lay’s parents were quickly losing control of the situation. And though they brought him to see doctors, Lay said the treatments didn’t work. Outside the home, he started fighting more, and stealing—first little things, then cars. Later, he joined a gang and quickly became mixed up in the violence. One day, after being beaten by rivals, Mel insisted Lay act. Approaching the 20-year-old he thought led the attack, Lay took out a gun and shot him. The police later caught Lay and charged him with first-degree murder. He was 15. Into adulthood and confinement It would take Lay decades to learn he has schizoaffective disorder. With this mental illness, symptoms of schizophrenia, such as hallucinations or delusions, occur at the same time as symptoms of a mood disorder, such as depression or mania. Although Lay acted violently, most people with schizophrenia are not violent or dangerous, said Sarah Morris, Ph.D., Chief of the Adult Psychopathology and Psychosocial Interventions Research Branch at the National Institute of Mental Health (NIMH). As Lay’s mental illness played a role in the shooting, the court found him incompetent to stand trial by reason of insanity. In hopes of providing the teen with treatment, the judge sentenced Lay to 2 years in a state maximum-security mental health facility. While the measure had the potential to help, Lay said he had difficulties adjusting to the realities of long-term confinement. He also said that staff mistreated him and would tie him down, place him in straitjackets, or lock him in padded rooms. Some of the ineffective and harmful practices of the past created a stigma for psychiatric treatment. Dr. Morris said that stigma still exists today and inhibits some people from getting the help they need. However, treatment for schizophrenia has improved since then, she added. “There are many more medications now with better options for managing side effects,” she said. “Also, many clinics now use a coordinated specialty care approach, where teams of providers work together with patients and their families to provide care that includes psychotherapy, medication management, family education and support, service coordination, case management, and supported employment and education services.” While mental health care has improved since then, Lay didn’t have the advantage of modern treatments for psychosis. His treatment at the maximum-security facility would remain unchanged, and through this process, facility staff shepherded Lay into adulthood. Reentering the free world at 18, Lay dropped out of school and later joined the military. He thrived there for a few years, but was discharged after a psychotic break. Without a purpose, Lay lost his way and embarked on a crime spree that ended after police arrested him for robbing a man of empty bottles. This time, there would be no insanity plea. In considering Lay’s prior record, the judge sentenced Lay to 12 years in a maximum-security prison. He wouldn’t emerge from prison until he was 31. Life on the streets Once free, Lay sought to reinvent himself. He got married and moved to Indianapolis, which offered steady work. But remaining untreated, the symptoms of his mental illness never left. “I was trying to make a life, but … I was a functioning drug addict and alcoholic with a mental health condition,” Lay said. “I was paying the bills, going to work, but I was messing up at work, I was messing up at home, and … I didn’t realize it then, but treatment is really what I needed.” On the advice of his mother, Lay moved back to his hometown. But the situation was untenable. Cycling between drug abuse and psychotic breaks, Lay became unhoused. Sometimes, he’d couch surf or burn through his disability checks to get off the streets, but mostly, he bounced in and out of homelessness. He lived like that for 12 years. While those close to him reached out, Lay denied his addictions. And though nearing 50, he still didn’t realize he had schizoaffective disorder. “I didn’t accept it,” Lay said of his mental illness. “I felt … a sense of straddling the fence, with some hole in the role of me.” Then, a chance encounter changed everything. What is schizophrenia? One day, while in a shelter, a clinical social worker approached Lay and asked if he was in treatment for schizophrenia. “What is schizophrenia?” he asked. The conversation opened doors, and for the first time in his life, Lay voluntarily enrolled in treatment. While other doctors had talked “at him,” this new one listened, allowing Lay to open up. In doing so, he began to heal. “Do not be afraid to talk with a mental health provider—and I mean, talk,” he said. “Let them have your deepest, darkest so-called secrets, because I have found that giving mine away has helped me get a whole lot better.” His psychiatrist prescribed medication, and this time, Lay stuck with it. Though adjusting to the side effects wasn’t easy, Lay said his desire to “live life” outweighed all else. “While it might be initially frustrating, finding a treatment that works can have life-changing outcomes, especially if doctors catch the disorder early,” Dr. Morris said. “Modern treatment plans—developed with the patient’s input and goals in mind—help many people with schizophrenia and related disorders lead rich and fulfilling lives.” As for Lay, therapy taught him how to work with his thoughts, feelings, and behaviors. In accepting his situation, his past, his challenges—everything started making sense. Therapy also helped Lay get off drugs and alcohol. Recently, he marked 16 years of sobriety. While he still faces challenges, he approaches them differently. “I sometimes still talk to my voices, and when I do talk with them now, I know that they are not real,” he said. “But I realized that I need to keep taking my medication, stay away from illegal drugs and alcohol, and don’t miss none of my appointments: In other words, I need to stay in treatment.” After making significant progress with his recovery, doctors felt Lay was ready to live a more independent life. In 2011, Lay took charge of his finances and secured an apartment, ending 12 years of homelessness. Helping others Between hospitalization, incarceration, and homelessness, Lay lost more than two decades of his life. Having missed out on so much, he tries to make up for it. Lay began the new chapter of his life about 8 years ago, successfully running for a seat on the National Alliance on Mental Illness (NAMI), Indiana Board of Directors. He later earned a seat on NAMI’s national board, where he's worked to further outreach about mental illnesses. Lay also began working as a peer support specialist at the Department of Veterans Affairs, where he’s spent over 5,000 hours helping other veterans work through mental illness. Now 68, while some people would be relaxing in retirement, Lay runs a business giving presentations on mental health. “I get to take my sorrow, my pain, my hurt, my tears, and help others,” he said. “I get to go to some of the places I was incarcerated and hospitalized, and talk with some of the first responders and try to prepare them for what they might encounter.” Much of his work seeks to bridge the gap of misunderstanding with law enforcement—his message: A little compassion goes a long way. “I try to instill in the police that persons with mental health issues are still persons,” he said. Recently, Ken Duckworth, M.D., Chief Medical Officer of NAMI, featured Lay in his book, “You Are Not Alone.” Reflecting on his journey with mental illness, Lay told Dr. Duckworth that helping people gives him purpose. It’s his way, in part, of trying to forgive himself. Through treatment, Lay’s become a better man. And for as long as he can, he wants to give back. In reclaiming the kindness in his soul, Lay’s rediscovered who he was meant to be. He’s also now able to do something once unthinkable: connect with people. He’s married to his wife, Dianna. They own a house in Indianapolis and care for their pet Chihuahua, Bentley. He spends his days busy, optimistic, and trying to do good in the world. It’s all he ever wanted.