Risks of Clozapine Decline Sharply After Six Months, May Warrant Reduced Monitoring

While clozapine increases an individual’s risk of agranulocytosis (a drop in a type of white blood cell that can be life threatening) more than other antipsychotics, the risk of a serious adverse event is minimal and drops steeply after the first year of use, according to a study published yesterday in Lancet Psychiatry. This study, which tracked nearly 62,000 people in Finland for up to 22 years, also found that the fatality rate among individuals who develop agranulocytosis is very low.

“More than half of the agranulocytosis events in patients treated with clozapine occurred during the initial 6 months,” wrote Jose M. Rubio, M.D., of the Feinstein Institutes for Medical Research in Manhasset, N.Y., and colleagues. “Notably, although purposeful, lifetime blood monitoring might be a deterrent to use clozapine for some patients and therefore lifting it from being mandatory after a cautionary period could facilitate the uptake of this underused drug.”

Rubio and colleagues studied 61,679 people who were diagnosed with schizophrenia or schizoaffective disorder in Finland, which has the highest rate of clozapine prescription worldwide. About one-quarter the individuals took clozapine, and three-quarters took other antipsychotics.

The researchers noted that antipsychotics as a class appear to be associated with an elevated risk of agranulocytosis during the initial six months of treatment. In fact, 231 individuals treated with clozapine developed the condition (1.37%) as well as 167 individuals treated with other antipsychotics (0.13%). However, the risk of agranulocytosis appeared to abate after six months among those taking other antipsychotics, while the risk of developing clozapine-induced agranulocytosis decreased steeply over time but remained elevated.

The researchers found an increased risk of agranulocytosis for those treated with higher than standard doses of clozapine, those taking it in combination with other psychotropic medication, and those with medical comorbidities. For every 3,559 individuals who initiated clozapine, only one person died due to agranulocytosis.

“Rubio and colleagues make a sensible, and cautious, call for a reduction in the frequency of blood monitoring for those on clozapine and to stop after 3 years of treatment,” according to an accompanying editorial by Jack B. Fanshawe and Belinda R. Lennox, D.M., of the University of Oxford. However, given the homogeneity of the Finnish population, “[f]urther studies in more diverse clinical cohorts are crucial to ensure any flexibility in haematological monitoring can be safely applied to these populations,” they wrote.

For related information, please see the Psychiatric News story, “FDA Reviewing Clozapine REMS to Determine if Monitoring Requirements Can Be Modified.”

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Young Adults Often Know Signs of Opioid Overdose, but Not How To Give Naloxone

A majority of young adults can correctly identify at least one sign of opioid overdose, but relatively few know how to administer naloxone, a study in JAMA Pediatrics has found.

Christina E. Freibott, M.P.H., of the Boston University School of Public Health and colleagues examined data from 7,071 young adults aged 18 to 25 attending an institution of higher learning who participated in the 2021-2022 Healthy Minds study. The participants answered four questions adapted from the Opioid Overdose Knowledge Scale and the Opioid Overdose Attitudes Scale about the following:

• What naloxone is used for.
• What the signs of opioid overdose are.
• Whether the participants knew how to use naloxone.
• Whether participants would be concerned about calling emergency services during an overdose event in case they got into trouble with their school or the police came.

The researchers found the following:

• 30.2% of participants correctly identified what naloxone is used for.
• 61.9% of participants correctly identified at least one sign of opioid overdose.
• 14.2% of participants reported knowing how to administer naloxone.
• 66.8% of participants felt comfortable calling emergency services during an overdose event.

There were significant differences in responses to all four questions based on race and ethnicity, gender identity, and sexual orientation. For example, participants who identified as Alaska Native or Pacific Islander were more likely to be knowledgeable about naloxone, correctly identify a sign of overdose, and be willing to intervene in an emergency than other racial and ethnic groups. Participants who identified as transgender or gender-expansive were more knowledgeable about naloxone compared with people who identified as males or females, but less likely to call emergency services. People who identified as lesbian, gay, bisexual, or queer were more knowledgeable about naloxone than heterosexual participants, but also less likely to call emergency services.

“Future research should explore person-centered approaches, clustering [young adults] into clinically meaningful subgroups to inform prevention and educational initiatives for a population experiencing increases in overdose fatalities,” Freibott and colleagues concluded.

For related information, see the Psychiatric News article “AMA Backs Making Overdose Reversal Meds Accessible in Schools.”

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People With Long COVID Have Greater MH Care Needs yet Face More Barriers

Adults with persistent COVID-19 symptoms are about twice as likely to report psychiatric problems such as depression, anxiety, or cognitive difficulties versus other adults, reports a study in JAMA Network Open. Yet these adults with post–COVID-19 condition (PCC) are also more likely to report cost barriers to mental health treatment that delayed or inhibited their care.

“People with PCC may have more difficulty paying for counseling or therapy due to lost employment wages and greater costs of managing complications from COVID-19, or they may experience challenges obtaining health plan authorization for these supports,” wrote Hiten Naik, M.D., of the University of British Columbia in Vancouver, and colleagues.

Haik and colleagues examined responses from the 2022 National Health Interview Survey; this was the first year this nationally representative U.S. survey had questions about PCC. Their final sample included 25,122 participants, of whom 844 had PCC at the time they took the survey. PCC was defined as the continued presence of one or more new-onset symptoms following coronavirus infection at least three months later.

The participants with current PCC were more likely to be female, White, and unvaccinated and have medical comorbidities. However, after adjusting for these factors and other variables, the researchers found that compared with the general adult population, those with PCC were

• 1.96 times as likely to report moderate or severe depression.
• 2.21 times as likely to report moderate or severe anxiety.
• 1.95 times as likely to report sleep difficulties.
• 2.04 times as likely to report cognitive difficulties.
• 1.85 times as likely to report disabling fatigue.

Despite the greater rate of depression and anxiety among adults with PCC, these adults were no more likely to have received medications, counseling, or behavioral therapy within the past year than the general population. Adults with PCC were about twice as likely to report they had to delay or not receive counseling or therapy from a mental health professional because of cost.

“At the health system level, it may be useful for health care leaders to prioritize the inclusion of affordable mental health supports when designing care pathways for PCC,” Haik and colleagues concluded.

For related information, see the Psychiatric News article, “Psychiatrists Vital to Care of Patients With Long COVID.”

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CBT More Effective Than Mindfulness for Prolonged Grief Symptoms Over Time, Study Finds

Both grief-focused cognitive-behavioral therapy (CBT) and mindfulness-based cognitive therapy improved patients’ symptoms of prolonged grief disorder immediately after 11 weeks of treatment, according to a study published yesterday in JAMA Psychiatry. Grief-focused CBT, however, was more effective in reducing patients’ symptom severity six months after treatment ended.

“[B]etween 15% and 25% of patients with prolonged grief disorder offered grief-focused cognitive behavior therapy decline to participate in treatment, and between 17% and 50% may not respond to treatment,” wrote Richard A. Bryant, Ph.D., of the University of New South Wales in Australia and colleagues. “A viable means to advance treatment of prolonged grief disorder is to evaluate therapeutic options that do not explicitly evoke distress through loss-focused strategies.”

Bryant and colleagues recruited 100 adults (87% female) aged 18 to 70 with prolonged grief disorder; diagnoses were made using ICD-11 criteria as this study was conducted prior to DSM-5-TR. Participants were evenly randomized to receive either grief-focused CBT or mindfulness-based cognitive therapy. Both interventions consisted of 11 weekly, 90-minute individual sessions. Grief-focused CBT included psychoeducation about prolonged grief disorder, cognitive reframing of maladaptive grief-related thoughts, and activities that promoted positive memories of the deceased. Mindfulness-based cognitive therapy included meditation, descriptions of how mindfulness could be used to tolerate aversive emotions and thoughts, and how to use mindfulness practices to manage grief reactions or to focus on positive memories.

Grief symptoms were assessed at baseline, one week after treatment, and six months later with the Prolonged Grief–13 (PG-13) scale, with possible scores ranging from 11 to 55. The authors also assessed depressive symptoms and grief-related cognition.

At baseline, the grief-focused CBT group had an average score of 43.6 on the PG-13 scale compared with 40.6 in the mindfulness group. Both interventions were associated with symptom improvement immediately after treatment, with PG-13 scores falling to 31.2 in the grief-focused CBT group and 29.5 in the mindfulness group. At six months, the average score in the grief-focused CBT group was 28.7, suggesting sustained improvement, compared with 32.8 in the mindfulness group. Similarly, though participants in both groups showed improvements in depressive symptoms and grief-related cognition one week after treatment, those in the grief-focused CBT group showed greater reductions in both measures six months later.

“Despite the superior gains made by participants in the grief-focused cognitive behavior therapy group, it is noteworthy that across both treatment groups there was a significant reduction in prolonged grief disorder symptoms,” the authors wrote. “It is possible that while mindfulness-based cognitive therapy afforded symptom relief for the duration of the trial, this emotion regulatory approach did not lead to longer-term gains because memories of the death and core beliefs about the loss were not directly targeted.”

For related information, see the Psychiatric News article “Special Report: Prolonged Grief Disorder—What You Need to Know.”

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Very Young Children Exposed to Anesthesia May Be at Higher Risk of Childhood Bipolar Disorder

Infants and toddlers who are exposed to general anesthesia may be at increased risk for bipolar disorder later in childhood compared with infants and toddlers who are not exposed, according to a report in Schizophrenia Bulletin. The association remained after adjusting for other childhood comorbidities and parental psychiatric diagnoses.

“In the context of pediatric care, it is essential to recognize the substantial perioperative trauma experienced by children, both physically and psychologically,” wrote Mingyang Sun, M.D., of the People’s Hospital of Zhenghzou University in Henan, China, and colleagues. “Emerging evidence underscores the significant impact of early-life exposure to multiple anesthetics on neurodevelopment.”

The researchers compared the incidence of pediatric bipolar disorder in 7,535 children in Taiwan who were exposed to general anesthesia at age 3 or younger between 2004 and 2014 with that of an equal number of children who were not exposed. Data were drawn from the Taiwan Maternal and Child Health Database. The two groups of children were matched for other variables associated with bipolar risk, including premature birth, head injury, sexual abuse, malnutrition, toxic exposure, congenital abnormalities, and parental psychiatric illness.

A total of 223 (3%) of the children who were exposed to general anesthesia were diagnosed with bipolar disorder before age 12 compared with 178 (2.4%) of those who were not exposed. Children exposed to general anesthesia were 1.26 times more likely to develop bipolar disorder before age 12.

Sun and colleagues noted that general anesthesia’s potential to increase the risk of developing bipolar disorder involves intricate mechanisms, including neurotoxicity associated with specific anesthetic agents and disruptions in neural pathways. Sevoflurane, a commonly employed inhalation anesthetic, has garnered particular attention due to its neurotoxic effects, they wrote, but adding, “our study didn’t examine specific anesthetic agents’ effects on [bipolar disorder] development, an area ripe for future research to inform precise anesthesia choices and mitigate [bipolar disorder] risk in children.”

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Peer-Supported Problem-Solving May Help Older Rural Adults With Depression

Older adults who completed 12 weeks of self-guided problem-solving therapy (PST) supported by trained peer volunteers had significant and lasting improvements in their depression scores, according to a report in Psychiatric Services in Advance. PST is a psychotherapy that teaches people to generate realistic solutions to life problems that contribute to depression.

“PST with a clinician should be considered a preferred treatment option when resources are available,” wrote Brooke Hollister, Ph.D., at the University of California, San Francisco, and colleagues. However, self-guided-PST supported by trained peer counselors “may be an appropriate and acceptable alternative to [clinician-managed]-PST (or other evidence-based interventions) for older adults who live in rural areas and experience barriers to access because of stigma, poor transportation options, or a lack of available clinicians and services.”

A total of 105 rural Californians aged 60 or older who had moderate to severe unipolar depression but did not have psychotic depression, a high suicide risk, or other major psychiatric disorders participated in the study. Eighty-five participants received clinician-managed PST with specially trained master’s level therapists or social workers, while the remaining 20 embarked on self-guided PST supported by peers who had also received special training. Both groups completed the PST sessions in their homes.

Depression levels were assessed with the Hamilton Depression Rating Scale [HAM-D]. Improvements in depression were clinically significant in both groups after 12 weeks, though clinician-managed PST did lead to higher response, remission, and retention rates, the researchers reported. Still, 45% of the adults in the peer-supported, self-guided group showed a treatment response of at least 50% reduction in HAM-D scores by week 12.

At 24 weeks, the groups equalized as the rates of depression reported by the self-guided group continued to drop, while the clinician-managed group’s depression scores rose slightly. This finding might imply a longer-lasting impact of self-guided treatment, given its focus on empowering patients to address their own problems, the researchers wrote. However, because the completion rate was lower for this group, Hollister and colleagues recommended further research to explore why.

“Effective use of [trained peer counselors] to support evidence-based treatments has the potential to maintain the independence of rural older adults by improving their access to mental health services and using existing infrastructure and minimal community resources,” they concluded.

For related information, see the Psychiatric Services article “Opportunities and Challenges to Build Behavioral Health Crisis Capacity in Rural America,” also published today.

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Overactive Bladder Linked to Depressive Symptoms

People who have been diagnosed with overactive bladder are nearly three times as likely to have depression than those without overactive bladder, a study in the Journal of Affective Disorders has found.

Xiansheng Zhang, M.D., Ph.D., of Anhui Medical University in Hefei, China, and colleagues examined responses from adults who participated in the National Health and Nutrition Examination Survey from 2005 to 2018 and who had complete data related to depression and urinary function. The researchers excluded adults who had conditions that could affect their urination, such as pregnancy, benign prostate issues, certain cancers, or stroke.

The final sample included 6,612 participants, among whom 1,005 had a diagnosis of overactive bladder. Overactive bladder was defined as a measurement of at least three on the Overactive Bladder Symptom Score, which includes questions about urinary incontinence and nocturia (waking up at night to urinate). Symptoms of depression were defined as a score of at least 10 on the nine-item Patient Health Questionnaire.

After adjusting for sociodemographic factors, behavioral factors (BMI, smoking status, alcohol use), and chronic diseases, the researchers found that participants with overactive bladder were 2.89 times more likely to have depressive symptoms than those without overactive bladder.

“[U]rinary incontinence symptoms…can affect social functioning and an individual's quality of life, such as decreased participation in social activities and loneliness, which can then lead to depression,” Zhang and colleagues wrote.

The researchers noted that the relationship between overactive bladder and depressive symptoms can go in both directions. First, the more severe overactive bladder symptoms were, the more likely participants were to have depression. Second, depressive symptoms may make overactive bladder symptoms worse.

“For psychiatrists, this underscores the importance of proactively assessing urinary system symptoms in patients with depression to improve treatment adherence and effectiveness, offering a more holistic approach to patient care,” they wrote.

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One in Four People With Schizophrenia or Bipolar Have Multiple Physical Health Problems

A study in Lancet Psychiatry reports that adults with schizophrenia or bipolar disorder are more than twice as likely as those without these disorders to have multiple physical health problems like heart disease or diabetes. Further, the presence of multiple physical problems was more common in adults with schizophrenia or bipolar disorder than the presence of multiple psychiatric disorders.

“While health services and treatment guidelines often operate on the assumption that individuals have a single principal diagnosis, these results attest to the clinical complexity many people with severe mental illness face in relation to burden of chronic disease,” wrote Sean Halstead, M.D., of the University of Queensland in Brisbane, Australia, and colleagues.

Halstead and colleagues collected data from 82 observational studies of adults with schizophrenia spectrum disorder or bipolar disorder that assessed the prevalence of co-occurring physical or psychiatric conditions (though only a few studies examined both). The combined data included more than 1.6 million adults with one of these disorders and over 13 million adults with neither disorder (controls).

Overall, 25% of adults with schizophrenia or bipolar disorder had two or more physical health problems, while 13% had three or more physical health problems. In comparison, 14% of these adults had two or more psychiatric problems (on top of their index diagnosis). The prevalence of multiple physical health problems was roughly the same for schizophrenia and bipolar.

After analyzing data from 11 studies of physical problems that included controls, the researchers calculated that compared with controls, adults with schizophrenia or bipolar disorder had 2.4 times the odds of having two or more physical health problems. The burden was even higher in adults 40 or younger, who had 4 times the odds of multiple physical health problems.

Halstead and colleagues suggested that “a nuanced combination” of multiple factors likely contributes to the poor physical health of young adults with schizophrenia or bipolar disorder, including genetics, prenatal exposures, lifestyle choices, and psychotropic medication side effects. This greater lifetime exposure to poor physical health may explain the high rates of premature mortality seen in people with these two disorders.

For related information, see the Psychiatric News article, “Award Winner Describes Efforts to Improve Cognition in People With Bipolar Disorder.”

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Most People Experiencing Homelessness Have Mental Health Disorders, Study Finds

Sixty-seven percent of people experiencing homelessness worldwide have a mental health disorder, according to a report published yesterday in JAMA Psychiatry. Additionally, the prevalence of mental health disorders among this population appears to be on the rise.

“The relationship between mental health disorders and homelessness is complex and bidirectional,” wrote Rebecca Barry, Ph.D., of the University of Calgary and colleagues. “[M]ental health disorders may lead to situations that result in homelessness, or homelessness may be a stressor contributing to the development or worsening of mental health disorder symptoms.”

Barry and colleagues combined data from 85 studies that investigated the current and/or lifetime prevalence of mental health disorders among adults aged 18 and older experiencing homelessness. The combined sample included 48,414 adults (77% male) from 19 countries—though about half the studies were from the U.S. or Canada.

The current prevalence of mental health disorders among people experiencing homelessness was 67%, while the lifetime prevalence was 77%. Additional findings included the following:

• Males experiencing homelessness had a significantly higher lifetime prevalence of mental health disorders (86%) compared with females (69%).
• Substance use disorders (including alcohol) were by far the most prevalent disorder identified, with a current prevalence of 44% and a lifetime prevalence of 56%.
• Antisocial personality disorder was the second most common disorder, with a current prevalence of 26%, followed by major depression (19%), general mood disorders (18%), anxiety disorders (14%), psychotic disorders (14%), posttraumatic stress disorder (11%), bipolar disorder (8%), and schizophrenia (7%).
• North America had the highest prevalence of mental disorders among people experiencing homelessness at 77% compared with Australia (47%), Asia (59%), and Europe (60%).

The authors also found that the prevalence of mental health disorders among people experiencing homelessness was higher in studies published after 2010 compared with those published earlier (76% vs 48%). They called this an important finding and posited that people with mental health disorders may be at increased risk of experiencing homelessness due to factors like housing affordability, limited access to care, low income, and problems reintegrating after receiving inpatient treatment.

“Conversely, the increase in prevalence could be the result of people experiencing homelessness being more likely to develop a mental health disorder due to stressors related to being unhoused, given the bidirectional relationship,” the authors continued. “Regardless, our finding that there is increasing prevalence of mental health disorders among people experiencing homelessness is concerning and effective strategies are needed to address the significant mental health needs of this population.”

For related information, see the Psychiatric News article “M.D.s Call for Community Resources Amid Plans to Force Homeless Into Care.”

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Access to In-Network Mental Health Care Still Lags Far Behind Other Medical Care

Patients are far more likely to go out of network to obtain health care from mental health professionals than from medical or surgical professionals, a report by RTI International has found.

In research that was partially funded by APA, Tami L. Mark, Ph.D., M.B.A., and William J. Parish, Ph.D., M.A., analyzed enrollment data and claims from more than 22 million individuals captured annually from 2019 through 2021 to evaluate out-of-network use and reimbursement rates across all 50 states.

The researchers found that patients went out of network 3.5 times more often to see a behavioral health professional (physician or nonphysician) than to see a medical or surgical professional. Patients went out of network 8.9 times more often to see a psychiatrist than another specialty physician, and 6.9 times more often to see a psychiatrist than a primary care physician.

The researchers also found that reimbursement for an in-network office visit was 22% higher for medical and surgical professionals than office visits with behavioral health professionals. Notably, physician assistants were reimbursed for office visits an average of 19% higher than psychiatrists, while nurse practitioners were reimbursed about 8% higher than psychiatrists.

Mark and colleagues concluded that shortages of behavioral health professionals do not explain the disparities in out-of-network use and reimbursement. “The finding of large disparities for out-of-network use and reimbursement rates highlights that health plans are not using the same measures to improve the adequacy of their behavioral health provider networks as they do for medical networks,” Mark said in a statement.

“The report’s findings make it clear that health insurers must be held accountable for not complying with the Mental Health Parity and Addiction Equity Act and provide appropriate payment for the care offered by psychiatrists and other mental health professionals,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A. “Enforcing parity will increase participation in insurance plans among mental health professionals and therefore increase access to mental health care by making those services more affordable for patients.”

The researchers recommended that federal and state agencies develop standardized templates to identify and remedy parity violations. They outlined several methods for developing these templates, including the following:

• Comparing behavioral health and medical/surgical reimbursement rates using Medicare benchmarks to allow valid and accurate comparisons across the array of services.
• Evaluating reimbursement disparities by specific provider type.
• Using all procedure billing codes when evaluating out-of-network use and reimbursement disparities, and not just a few selected codes.

For related information, see the Psychiatric Services article “Patients’ Reasons for Using Out-of-Network Mental and General Medical Health Providers.”

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Generic Drug Combination Cuts Drinking in Adults With Severe Alcohol Use Disorder

Adults with severe alcohol use disorder (AUD) who took a combination of a generic antihypertensive and antihistamine reduced their daily alcohol consumption by about 24 grams—nearly the amount in two standard drinks—over those taking a placebo, according to a report in Addiction.

“Considering the small number of approved medications and current limited use of pharmacotherapy for AUD, all with limited-to-moderate efficacy, patients with AUD as well as their physicians [need] additional treatments,” wrote lead author Henri-Jean Aubin of the Université Paris-Saclay in Villejuif, France, and colleagues.

Aubin and colleagues suggested that cyproheptadine, an anti-allergic medication, and prazosin, which treats hypertension and urinary urgency, might work well together. The former targets receptors involved in impulsive behaviors, and the latter targets receptors related to cravings.

The researchers recruited 154 adults who met DSM-5 criteria for severe AUD and had a high-risk drinking level, defined as consumption of more than 60 grams of alcohol a day for men or 40 grams for women; a standard drink such as a bottle of beer, glass of wine, or shot of liquor contains 14 grams of alcohol.

Participants received 12 weeks of either a high dose medication regimen (10 mg prazosin plus 12 mg cyproheptadine daily), low dose regimen (5 mg prazosin plus 8 mg cyproheptadine daily), or placebo. All participants received brief, simple psychosocial support focused on treatment adherence and reduction of alcohol consumption. The researchers used alcohol consumption as the primary outcome because they noted that people with AUD are increasingly interested in drinking reduction goals rather than achieving abstinence.

After 12 weeks, participants taking the high or low dose regimen reduced their alcohol consumption by 23.6 grams and 18.4 grams more than the placebo group, respectively. A separate analysis of adults with a very high-risk drinking level (more than 100 grams of alcohol a day for men and 60 grams a day for women) showed that they experienced an even larger response to the high-dose treatment: These adults reduced their drinking by 29.8 grams a day on average over placebo.

Both dosing regimens were well tolerated; a review of all significant adverse events study-wide deemed them unlikely to be related to the study drugs.

“The promising efficacy of the combination of prazosin and cyproheptadine warrants prolonging this work with phase 3 trials,” the researchers concluded.

For related information, see the Psychiatric News article “Special Report: Psychiatrists Critical in Screening, Treatment of Alcohol Use Disorder.”

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Let APA Know of Buprenorphine Access Issues APA is in discussions with our partner medical societies about the challenges patients are facing in accessing buprenorphine due to the opioid settlements. If you are hearing about challenges, please reach out to us at practicemanagement@psych.org to share your stories. We will continue to advocate for access and reduced burdens of helping our patients receive the treatment they deserve.

Adult ADHD Linked to Later Lewy Body Disease, Cognitive Impairment

Adults with attention-deficit/hyperactivity disorder (ADHD) may be at increased risk of dementia and cognitive impairment compared with those without ADHD, according to a report in the American Journal of Geriatric Psychiatry. Adults with ADHD seem particularly susceptible to dementia associated with Lewy body disease, a disorder characterized by abnormal deposits of proteins called Lewy bodies in the brain that results in various forms of cognitive impairment, delirium-like symptoms, Parkinson’s-like movement problems, and hallucinations.

“Determining whether there is an association between ADHD and subsequent conversion to a specific type of dementia is important,” wrote lead author Ángel Golimstok, M.D., of Hospital Italiano, Buenos Aires, and colleagues. “This information could generate opportunities for prevention and early treatment.”

The researchers followed 161 patients with ADHD and 109 without ADHD aged 45 to 70 for an average of 12 years to determine the rates of dementia and cognitive impairment. Both groups presented at a neurology service between February 2, 2007, and December 31, 2012, because of cognitive complaints or a family history of cognitive impairment or ADHD. Patients in either group taking psychoactive drugs including ADHD medications were excluded, except for those taking a single benzodiazepine or hypnotic for insomnia.

At the end of the follow-up, 27 patients with ADHD developed dementia (16.8%) compared with just four patients in the non-ADHD group (3.7%). Of the 27 ADHD patients with dementia, 19 also had Lewy body disease. The incidence of non-amnestic mild cognitive impairment (MCI) was also higher in the ADHD group (108 patients) compared with the non-ADHD group (19 patients); many of these ADHD patients with MCI also had Lewy body disease, and the authors noted that Lewy body-related cognitive problems usually do not affect memory.

In fact, all the core symptoms of Lewy body disease were more prevalent in the ADHD group than the non-ADHD group: REM sleep behavior disorder, Parkinsonism, delusions and hallucinations, cognitive fluctuations, decreased sense of smell, and syncope (fainting).

“Future studies should determine if ADHD represents a prodromal phase of the disease or if it is a risk factor. The connection between ADHD and dementias, in general, seems to be related more to comorbidity with depression than to shared pathophysiological mechanisms,” the authors wrote.

For related information see the Psychiatric News article “Symptoms, Impaired Function of ADHD Often Persist Beyond Childhood.”

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Psychedelic Use in Psychiatry Requires Complex Informed Consent, Experts Say

While psychedelics are moving toward possible approval for clinical use for the treatment of mental disorders, the medical standards for integrating these substances into health care have lagged, according to a special report issued in JAMA Psychiatry.

Of particular concern is the establishment of norms for informed consent, an ethical and legal cornerstone of medicine, according to a special communication written by Mason Marks, M.D., J.D., of Florida State University; Rebecca W. Brendel, M.D., J.D., of Harvard Medical School; and colleagues.

“Psychedelics have unique properties that complicate the informed consent process. They often produce intense subjective experiences that are difficult to explain, predict, or comprehend, especially for psychedelic-naive individuals,” the authors wrote. “These effects can include profound perceptual changes or hallucinations, mood disturbances, paranoia, and an altered sense of self and reality.”

The authors proposed several essential components of informed consent that professionals need to address before administering psychedelics in clinical settings. These include the following:

• Advising patients about the potential for specific adverse events, such as acute and chronic perceptual changes, personality changes, and altered metaphysical beliefs.
• Establishing safeguards in advance of treatment around the potential use of limited physical touch in treatment, such as a reassuring touch of the shoulder.
• Advising about the increased risk of abuse, exploitation, or coercion during treatment and in the weeks or months after.
• Conveying the heightened social, legal, and professional risks associated with information that may be disclosed during a psychedelic state.
• Disclosing potential conflicts of interest or other relevant practitioner information.
• Creating more interactive education and consent processes to improve comprehension, such as consent quizzes to test knowledge or virtual reality content to simulate the experience.

An accompanying editorial by Paul S. Appelbaum, M.D., of the New York State Psychiatric Institute at Columbia University, points out that the proposed elements focus solely on the nature and risks of psychedelic treatment. “Although it would be difficult to quarrel with any of these suggestions, it is important to recognize that these elements are only part of a complete informed consent process.”

Applebaum pointed out that treatment questions pertaining to the optimal number of psychedelic episodes, the duration of response to psychedelic therapy, and the likelihood of response to psychedelic administration in the event of a relapse are all unknown. “At present, all that can—and should—be shared with patients is the profession’s uncertainty about these important issues,” he wrote.

Another source of uncertainty stems from the narrowly selected participant samples for most psychedelic research studies. Frequently excluded are people with personal or family histories of psychotic disorders, prior suicide attempts requiring hospitalization, manic episodes, or borderline personality disorders.

“Right now, there are essentially no data that can be enlisted to help such patients understand the unique risks, if any, that they may face,” Appelbaum wrote.

For related information, see the Psychiatric News article “Psychedelic Therapy Requires Enhanced Consent Discussions.”

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Let APA Know of Buprenorphine Access Issues APA is in discussions with its partner medical societies about the challenges patients are facing in accessing buprenorphine due to the opioid settlements. If you are experiencing or hearing about challenges, please email the details to APA. APA will continue to advocate for access and reduced burdens of helping patients receive the treatment they deserve.

Nonemergency ED Use Higher Among Infants of Mothers With Perinatal Depression, Study Finds

Compared with infants of mothers with no perinatal depression symptoms, those born to mothers with mild or moderate/severe symptoms were significantly more likely to have emergency department (ED) visits for nonemergency reasons, according to a study published in Health Affairs.

“Perinatal mental health conditions affect 20% of birthing people and are associated with a range of adverse child outcomes, including increased ED use,” wrote Slawa Rokicki, Ph.D., M.S., of Rutgers University. “This may be a result of increased illness or injury due to biological effects of depression on infant health or inadequate infant care practices associated with parental depression. Alternatively, increased ED use may be due to overuse resulting from a lack of social support at home or low health literacy.”

Rokicki used data from the hospital records of 207,428 mothers who gave birth to non-twins in New Jersey between 2016 and 2018; New Jersey implemented universal depression screening for new mothers before hospital discharge in 2006. Most hospitals screened with the Edinburgh Postnatal Depression Scale. Rokicki categorized perinatal depression symptom severity as none (scores of zero to six), mild (scores of seven to 13), and moderate/severe (scores of 14 or greater).

She linked these data with infants’ ED discharge records during the first year of life. Infants’ primary diagnosis codes when discharged from the ED were used to determine if the visits were nonemergent or emergent.

A little over 10% of infants were born to mothers who had mild depressive symptoms at delivery, and just under 1% were born to mothers with moderate/severe depressive symptoms. Additional findings included the following:

• In total, 68.4% of ED visits among infants were classified as nonemergent.
• Infants born to mothers with moderate/severe depressive symptoms had an average of 1.05 ED visits, both emergent and nonemergent, during the first year, compared with 0.82 among those born to mothers with mild symptoms and 0.70 among those born to mothers with no symptoms.
• Similarly, infants born to mothers with moderate/severe depressive symptoms had an average of 0.6 nonemergent ED visits during their first year, compared with 0.48 among those born to mothers with mild symptoms and 0.41 among those born to mothers with no symptoms.
• Infants whose deliveries were paid for by Medicaid had an average of 1.24 ED visits in the first year compared with 0.41 visits among those with commercial insurance.

After adjusting for demographic, economic, and birthing (for example, preterm birth or need for a C-section) differences among the groups, there remained a significant association between perinatal depressive symptoms and increased nonemergent infant ED visits, but not emergent visits.

“Medicaid is the primary payer for more than 60 percent of pediatric ED visits, and this proportion has been steadily rising,” Rokicki concluded. “Implementing policies that interrupt the relationship between perinatal depression and nonemergent ED use is therefore an important priority with potential for cost savings.”

For related information, see the Psychiatric News article “In Addressing Maternal Mortality, Mental Health Often Left Out.”

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Suppressing Emotions, Feeling Like a Burden Linked to Suicidal Behavior in Preteens

Preteen children who have more trouble expressing their feelings and who perceive themselves as a greater burden to others may be on the cusp of having suicidal thoughts and behaviors (STB), according to a report in the Journal of the American Academy of Child and Adolescent Psychiatry.

Increases in caregiver criticism and conflict are also risk factors for impending STBs, according to the study. Preteen girls with these traits are at especially high risk.

“Preadolescent STBs are dramatically increasing, and it is critical to identify risk factors that can be clinically assessed and modified with treatment,” wrote Renee Thompson, Ph.D., of Washington University, St. Louis, and colleagues.

The researchers analyzed the association between a host of psychosocial factors and suicidal thoughts and behaviors in 192 children aged 7 to 12; most of the children had participated in a clinical study of preadolescent depression, though some children who did not have depression were added as controls.

The participants completed a series of surveys that assessed suicidality and the following psychosocial risk factors:

• Depressive symptoms
• Positive and negative affect
• The ability to understand what one is feeling
• The sense of being disconnected from people and not belonging anywhere
• The perception that one is burdensome to others
• Criticism from and conflict with caregivers
• The ability or willingness to manage and/or express one’s feelings

The surveys were conducted weekly with children whose caregivers reported any incidents of suicidal thoughts or self-harm at baseline, or monthly otherwise, for 12 months. Participants were on average 10.13 years old and 63% male. Thirty percent met criteria for major depression, and 37.7% met criteria for another internalizing disorder. During the one-year time frame, 70 children screened positive for STBs.

Overall, girls were four times more likely than boys to report STBs, and boys and girls with severe depressive symptoms were 10 times more likely to have STBs than children with mild or moderate symptoms.

Thompson and colleagues then looked closer at the week-to-week responses of high-risk children—those with a history of STBs when entering the study. They found that at any given week, children who reported expressive suppression, perceived burdensomeness, and caregiver criticism and conflict above their historical average levels were more likely to have a positive STB report in the following week.

“The risks identified in the present study … may be useful to clinicians and important for future research to consider as potential targets for prevention and treatment aimed at decreasing STB risk,” the authors concluded.

For related information see the Psychiatric News article “Suicidal Thoughts Begin Early for Some Youth.”

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Study Finds No Link Between Acetaminophen Use During Pregnancy And Autism, ADHD Risk

Children exposed to acetaminophen in the womb do not appear to have an increased risk of autism or attention-deficit/hyperactivity disorder (ADHD), according to a study published today in JAMA. While a broad analysis of Swedish families found a slightly increased rate of these disorders in children exposed to acetaminophen in the womb, the researchers found no evidence acetaminophen was responsible when factoring in genetic or family influence.

“Results of this study indicate that the association between acetaminophen use during pregnancy and neurodevelopmental disorders is a noncausal association.,” wrote Viktor H. Ahlqvist, Ph.D., of the Karolinska Institutet and colleagues. “Results suggested that there was not one single ‘smoking gun’ confounder, but rather that multiple … health and sociodemographic characteristics each explained at least part of the apparent association.”

Ahlqvist and colleagues first examined developmental outcomes of nearly 2.5 million non-twin children born in Sweden between July 1, 1995, and December 31, 2019. The researchers followed the children until the end of 2021 and identified all diagnoses of autism, ADHD, and intellectual disability. Overall, 7.62% of these children were diagnosed with at least one of these neurodevelopmental disorders. The researchers found that children whose mothers used acetaminophen at some point during pregnancy had a 5% increased risk of an autism or intellectual disability diagnosis and a 7% increased risk of an ADHD diagnosis.

However, mothers who used acetaminophen were more likely to have lower education and/or income levels, have a higher body mass index during early pregnancy, smoke during pregnancy, and have a psychiatric diagnosis. The researchers tried to account for these variables and many others (like the use of other pain medications) in their analysis but noted there might be some genetic or family factors they couldn’t account for.

So, as a further step, Ahlqvist and colleagues conducted a sibling control analysis in which they examined families with siblings in which some children were exposed to acetaminophen while others were not. In this model, they found no association between acetaminophen use during pregnancy and risk of a neurodevelopmental disorder. (In an unexpected result, they did find that the use of aspirin was associated with a reduced risk of neurodevelopmental disorders in children; the researchers hypothesized this association reflected individuals who took low-dose aspirin to reduce birthing problems like preeclampsia.)

For related information, see the Psychiatric News stories “Exposure to Valproate in Utero May Increase Risk of Autism, ADHD” and “Most Antipsychotics During Pregnancy Do Not Increase Neurodevelopmental Risks.”

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APA Opposes Efforts to Ban Diversity Initiatives in Medical Education

On Friday APA issued a statement opposing efforts to ban diversity, equity, and inclusion (DEI) programs and initiatives in medical education.

“In today’s medical schools and academic psychiatry departments, the principles of diversity, equity, and inclusion are critical to ensure that the next generation of physicians can serve the needs of evolving, diverse, underrepresented, and underserved patient populations,” the statement said.

“Recently, there have been efforts to ban these principles in colleges and universities. This presents a chilling and undesirable development that restricts the ability of medical students and residents studying psychiatry to explore the various factors that impact mental health and wellness,” the statement continued.

According to a DEI legislation tracker by the Chronicle of Higher Education, 82 anti-DEI bills have been introduced in the states and Congress since 2023. Of these, 12 have become law; 12 have final legislative approval; and 35 have been tabled, failed to pass, or vetoed. The actions contained in the legislation include the following:

• Prohibiting colleges from having diversity, equity, and inclusion offices or staff.
• Banning mandatory diversity training.
• Forbidding institutions to use diversity statements in hiring and promotion policies.
• Barring colleges from considering race, sex, ethnicity, or national origin in admissions or employment.

Last summer, in a decision rendered in Students for Fair Admissions v. President and Fellows of Harvard College and Students for Fair Admissions v. University of North Carolina, the U.S. Supreme Court ruled 6-3 that the admissions programs at Harvard and the University of North Carolina that relied in part on racial considerations violate the Constitution’s guarantee of equal protection under the 14th Amendment. At the time, APA issued a statement against the decision, noting that race-conscious admissions policies are designed to address racial discrimination by recognizing and responding to the structural barriers that hinder access to higher education for underrepresented students.

In its current statement, APA said, “The abilities to discuss, to learn about, and to research topics such as diversity, equity, and inclusion, not limited to but certainly including protected classes such as race, ethnicity, gender, gender identity, gender expression, and sexual orientation, are essential to foster and ensure a culturally competent psychiatric workforce that can provide high quality care for all patient populations.”

For related information, see the Psychiatric News article “APA Speaks Out Against Supreme Court Ruling on Affirmative Action in Higher Education.”

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High Blood Glucose, Triglycerides Linked to Long-Term Risk of Mental Disorders

Individuals with elevated blood levels of glucose and triglycerides have an increased risk of depression, anxiety, and stress-related disorders, as do individuals with low blood levels of HDL cholesterol (“good cholesterol”), a study in JAMA Network Open has found. Further, elevated levels of glucose or triglycerides were present in individuals who developed one of these disorders as far back as 20 years prior to diagnosis.

Charilaos Chourpiliadis, M.D., of the Karolinska Institutet in Stockholm and colleagues analyzed data from 211,200 participants in the Apolipoprotein-Related Mortality Risk cohort who underwent occupational health screening between January 1, 1985, and December 31, 1996. As part of the screening, blood tests were done to measure glucose, total cholesterol, HDL cholesterol, LDL cholesterol (“bad cholesterol”), triglycerides and other markers of metabolic and cardiovascular risk. The researchers determined clinical cutoffs for these blood markers based on previous research and/or cardiovascular disease guidelines.

Study participants had a mean age of 42.1 years at their first screening and were followed for a mean of 21 years. The researchers examined the individuals’ diagnoses in the Swedish Patient Register to look for a first diagnosis of depression, anxiety, or stress-related disorders. They defined stress-related disorders as acute stress reaction, posttraumatic stress disorder, adjustment disorders, other reactions to severe stress, and unspecified reaction to severe stress.

Over the follow-up period, 16,256 individuals were diagnosed with depression, anxiety, or stress-related disorders, with a mean age at diagnosis of 60.5 years. The researchers found the following:

• Individuals with blood glucose levels of 110 mg/deciliter or higher had a 30% higher risk of depression, anxiety, and stress-related disorders compared to those with lower levels.
• Individuals with triglyceride levels of 150 mg/deciliter or higher had a 15% higher risk of these mental illnesses compared to those with lower levels.
• Individuals with HDL cholesterol levels of 40 mg/deciliter or higher had a 12% lower risk of these mental illnesses compared to those with lower levels.

“These results add further evidence of the association between cardiometabolic health and psychiatric disorders and potentially advocate for a closer follow-up of individuals with metabolic dysregulations for prevention and early diagnosis of psychiatric disorders,” the researchers wrote. “Additional studies are needed to explore whether rigorous or earlier interventions for cardiometabolic diseases could counteract such an association.”

For related information, see the American Journal of Psychiatry article “Genetic and Environmental Contribution to the Co-Occurrence of Endocrine-Metabolic Disorders and Depression: A Nationwide Swedish Study of Siblings.”

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Family History of Treatment-Resistant Depression May Be Risk Factor for Antidepressant Resistance

Individuals with a family history of treatment-resistant depression (TRD) have an increased risk of experiencing antidepressant resistance themselves, a study published yesterday in JAMA Psychiatry found. Further, individuals with a family history of TRD have a greater risk of other psychiatric illnesses and dying by suicide.

“In recent years, an increasing number of genetic studies have attempted to understand the genetic architecture of antidepressant response or TRD phenotype,” wrote Chih-Ming Cheng, M.D., of the Taipei Veterans General Hospital in Taiwan and colleagues. “Although the efforts to understand the genetic mechanism behind antidepressant response are promising, these positive results require more replication and must overcome methodological concerns, such as relatively small sample size and diverse definitions of TRD.”

Cheng and colleagues used data from the Taiwan National Health Insurance program, which covers nearly the entire population of Taiwan and includes diagnoses of psychiatric disorders. The authors used all medical records from 2003 to 2017, which were linked to records from the Database of National Mortality Registry to determine date and cause of death. Patients who were diagnosed with major depressive disorder and received at least three adequate antidepressant trials (exceeding 56 daily doses in an eight-week period) within two years were defined as having TRD. In total, 21,046 individuals met these criteria. The authors then identified 34,467 first-degree relatives of those with TRD and matched them by birth year, sex, and kinship with 137,868 first-degree relatives of individuals without TRD.

Relatives of those with TRD had nine times the risk of developing TRD compared with those in the control group. They were also significantly more likely to develop other psychiatric illnesses, including schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, major depressive disorder, autism spectrum disorder, anxiety, and obsessive-compulsive disorder. These findings persisted even after controlling for factors such as birth year, sex, income, and comorbid conditions. Relatives of those with TRD also had a higher risk of all-cause and suicide mortality, and this risk remained even after excluding relatives who developed TRD from the analysis.

“Family history of TRD is a clinical risk factor due to its association with increased suicide mortality and resistance to antidepressant treatment; therefore, more intensive depression treatments, such as add-on pharmacotherapy or nonpharmacotherapy might be considered earlier, as opposed to antidepressants alone, for treating the symptoms of individuals with TRD,” the authors concluded.

For related information, see the Psychiatric News article “To Address Treatment-Resistant Depression, First You Have to Define It.”

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Clozapine, LAIs Found Effective in Patients With First-Episode Psychosis and Cannabis Use Disorder

Individuals with first-episode psychosis (FEP) and cannabis use disorder who were prescribed any antipsychotic were significantly less likely to be hospitalized for psychosis than similar patients who did not receive an antipsychotic, according to a report in Schizophrenia Bulletin.

Clozapine and long-acting injectable (LAI) formulations of risperidone, aripiprazole, and paliperidone were the most effective medications at preventing relapse and hospitalization due to psychosis. Clozapine was also most effective at preventing hospitalization due to substance use.

Alexander Denissoff, M.D., of the University of Turku, Finland, and colleagues noted that cannabis use is common among FEP patients. Further, continued cannabis use after a first episode of psychosis has been associated with more severe symptoms, nonadherence to antipsychotic treatment, and an increased frequency of relapse.

For that reason, “improving outcomes of FEP patients with dual disorders is of paramount importance as relapse after the index psychotic episode is associated with adverse clinical outcomes,” they wrote.

Denissoff and colleagues used Swedish national registries to track the outcomes of 1,820 individuals diagnosed with FEP and co-occurring cannabis use disorder between 2006 and 2021. The main outcome was hospitalization due to relapse of psychosis, though the researchers also looked for hospitalizations due to any substance use disorder.

A total of 1,111 of the 1,820 patients were hospitalized due to psychotic relapse. The researchers found that patients who received any antipsychotic were 33% less likely to be hospitalized due to a relapse of psychosis compared with patients who did not receive an antipsychotic. Regarding individual medications, LAI risperidone was associated with the most significant reduction in hospitalization risk (60%), followed by LAI aripiprazole (58%), oral clozapine (57%), and LAI paliperidone (54%). In contrast, LAI olanzapine, oral quetiapine, and oral risperidone were not found to prevent hospitalization due to relapse.

In the cohort, 1,143 of 1,820 patients were hospitalized due to substance use disorder. Clozapine was associated with the greatest decreased risk of subsequent hospitalization due to any substance use (86%) followed by LAI formulations of risperidone (67%) and paliperidone (63%).

“These findings encourage the early use of second-generation long-acting injectables as an important secondary pre­vention strategy to reduce rates of hospitalization in first-episode patients with comorbid cannabis use disorders,” the researchers concluded.

For related information, see the Psychiatric News article “Strategies for Reducing Cannabis Use By Patients With FEP.”

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Social Media Found to Be More Helpful to Children Today Than in 2022

While U.S. adults remain divided on the mental health impacts of social media, more parents view social media as helpful to their children’s mental health than they did two years ago. These are some of the findings from APA’s latest Healthy Minds Monthly Poll released today.

For example, 31% of parents in 2024 said they believe that social media has helped their child’s mental health, up from 24% in 2022; 31% of parents today also believe social media has helped their child’s self-esteem, up from 23% in 2022. These changes reflect fewer parents viewing social media as a neutral influence, as the number of parents who said social media hurts their child’s mental health has remained steady at 20% between 2022 and 2024.

This new poll also found changing perceptions of social media’s impact on society at large, with fewer respondents in 2024 saying that social media is hurting political or civil discourse compared with 2022.

“Social media is a ubiquitous technology, and our understanding of the harm it can cause is shifting,” said APA President Petros Levounis, M.D., M.A., in a news release. “Ultimately our personal use of social media is similar to the interaction we have with any technology, which is to say that we have to be mindful of its impact on our mood, thoughts, and feelings. Helping children and adolescents learn and practice mindfulness can give them skills to manage their journeys in social media.”

This year’s poll also showed that many respondents use social media to search for and/or share information on mental health. Younger adults were especially likely to use social media for such purposes; for example, 77% of 18- to 34-year-olds had used social media to find mental health information, compared with only 23% of adults ages 65 or older.

“It is no surprise that particularly younger Americans are listening and joining the social media conversation on mental health,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A., in the release. “In many ways, that is a very healthy sign. However, those of us in the mental health and medical fields must work to ensure that accurate information is available and that people can reach a doctor or other mental health clinician if they aren’t feeling well.”

This year’s poll was fielded by Morning Consult on behalf of APA between March 11 and 14 and included responses from 2,204 adults. The 2022 poll was fielded January 19 and 20, 2022, among a sample of 2,210 adults.

To read more on the impacts of social media, see the latest Psychiatric News special report,“Is Social Media Misuse a Bad Habit or Harmful Addiction?”

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