Mental Health

TOPLINE:

About one third of US adults aged 50-80 years report feeling lonely and socially isolated, a new study of data from 2018-2024 shows. While the levels have returned to the prepandemic range, investigators say the findings suggest clinicians should screen for loneliness and isolation.

METHODOLOGY:

• Researchers conducted a nationally representative survey of US adults aged 50-80 years through the University of Michigan National Poll on Healthy Aging at six timepoints between 2018 and 2024.
• Data collection involved online surveys conducted using the Ipsos KnowledgePanel from 2018 to 2021, transitioning to online and phone surveys conducted using the National Opinion Research Center AmeriSpeak panel from 2022 to 2024.
• Sample sizes ranged between 2051 and 2576 respondents, with completion rates ranging from 61% to 78% across the survey periods.

TAKEAWAY:

• Loneliness rates among adults aged 50-80 years showed notable fluctuation, starting at 34% (95% CI, 31.7%-36.2%) in 2018, rising to 41% (95% CI, 39.1%-43.7%) in 2020, and returning to 33% (95% CI, 31.7%-35.1%) by 2024.
• Social isolation showed a similar pattern in the study group, starting at 27% (95% CI, 24.5%-28.8%) in 2018, peaking at 56% (95% CI, 53.4%-58.1%) in 2020, and declining to 29% (95% CI, 27.5%-30.9%) by 2024.
• Higher loneliness and social isolation rates were frequently reported among individuals who did not work, lived alone, had lower household incomes, and had self-reported fair and poor physical and mental health than those who reported excellent, very good, or good health.

IN PRACTICE:

The findings suggest that “much like routinely asking about diet and exercise, clinicians should consider screening older adults for loneliness and social isolation and connect them with appropriate resources,” the investigators wrote.

SOURCE:

The study was led by Preeti N. Malani, MD, MSJ, University of Michigan Medical School, Ann Arbor. It was published online on December 9 in JAMA.

LIMITATIONS:

The study was limited by possible recall bias, reliance on self-reported data, lack of longitudinal results, and differences in survey timing, panels, and question framing across years. The findings may not have been applicable to excluded groups such as nursing home residents or individuals aged > 80 years, which limited their generalizability.

DISCLOSURES:

The study was supported by AARP and Michigan Medicine and the Department of Veterans Affairs, Veterans Health Administration, and Health Systems Research. One author reported receiving consulting fees and honoraria from various organizations. Details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About one third of US adults aged 50-80 years report feeling lonely and socially isolated, a new study of data from 2018-2024 shows. While the levels have returned to the prepandemic range, investigators say the findings suggest clinicians should screen for loneliness and isolation.

METHODOLOGY:

• Researchers conducted a nationally representative survey of US adults aged 50-80 years through the University of Michigan National Poll on Healthy Aging at six timepoints between 2018 and 2024.
• Data collection involved online surveys conducted using the Ipsos KnowledgePanel from 2018 to 2021, transitioning to online and phone surveys conducted using the National Opinion Research Center AmeriSpeak panel from 2022 to 2024.
• Sample sizes ranged between 2051 and 2576 respondents, with completion rates ranging from 61% to 78% across the survey periods.

TAKEAWAY:

• Loneliness rates among adults aged 50-80 years showed notable fluctuation, starting at 34% (95% CI, 31.7%-36.2%) in 2018, rising to 41% (95% CI, 39.1%-43.7%) in 2020, and returning to 33% (95% CI, 31.7%-35.1%) by 2024.
• Social isolation showed a similar pattern in the study group, starting at 27% (95% CI, 24.5%-28.8%) in 2018, peaking at 56% (95% CI, 53.4%-58.1%) in 2020, and declining to 29% (95% CI, 27.5%-30.9%) by 2024.
• Higher loneliness and social isolation rates were frequently reported among individuals who did not work, lived alone, had lower household incomes, and had self-reported fair and poor physical and mental health than those who reported excellent, very good, or good health.

IN PRACTICE:

The findings suggest that “much like routinely asking about diet and exercise, clinicians should consider screening older adults for loneliness and social isolation and connect them with appropriate resources,” the investigators wrote.

SOURCE:

The study was led by Preeti N. Malani, MD, MSJ, University of Michigan Medical School, Ann Arbor. It was published online on December 9 in JAMA.

LIMITATIONS:

The study was limited by possible recall bias, reliance on self-reported data, lack of longitudinal results, and differences in survey timing, panels, and question framing across years. The findings may not have been applicable to excluded groups such as nursing home residents or individuals aged > 80 years, which limited their generalizability.

DISCLOSURES:

The study was supported by AARP and Michigan Medicine and the Department of Veterans Affairs, Veterans Health Administration, and Health Systems Research. One author reported receiving consulting fees and honoraria from various organizations. Details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About one third of US adults aged 50-80 years report feeling lonely and socially isolated, a new study of data from 2018-2024 shows. While the levels have returned to the prepandemic range, investigators say the findings suggest clinicians should screen for loneliness and isolation.

METHODOLOGY:

• Researchers conducted a nationally representative survey of US adults aged 50-80 years through the University of Michigan National Poll on Healthy Aging at six timepoints between 2018 and 2024.
• Data collection involved online surveys conducted using the Ipsos KnowledgePanel from 2018 to 2021, transitioning to online and phone surveys conducted using the National Opinion Research Center AmeriSpeak panel from 2022 to 2024.
• Sample sizes ranged between 2051 and 2576 respondents, with completion rates ranging from 61% to 78% across the survey periods.

TAKEAWAY:

• Loneliness rates among adults aged 50-80 years showed notable fluctuation, starting at 34% (95% CI, 31.7%-36.2%) in 2018, rising to 41% (95% CI, 39.1%-43.7%) in 2020, and returning to 33% (95% CI, 31.7%-35.1%) by 2024.
• Social isolation showed a similar pattern in the study group, starting at 27% (95% CI, 24.5%-28.8%) in 2018, peaking at 56% (95% CI, 53.4%-58.1%) in 2020, and declining to 29% (95% CI, 27.5%-30.9%) by 2024.
• Higher loneliness and social isolation rates were frequently reported among individuals who did not work, lived alone, had lower household incomes, and had self-reported fair and poor physical and mental health than those who reported excellent, very good, or good health.

IN PRACTICE:

The findings suggest that “much like routinely asking about diet and exercise, clinicians should consider screening older adults for loneliness and social isolation and connect them with appropriate resources,” the investigators wrote.

SOURCE:

The study was led by Preeti N. Malani, MD, MSJ, University of Michigan Medical School, Ann Arbor. It was published online on December 9 in JAMA.

LIMITATIONS:

The study was limited by possible recall bias, reliance on self-reported data, lack of longitudinal results, and differences in survey timing, panels, and question framing across years. The findings may not have been applicable to excluded groups such as nursing home residents or individuals aged > 80 years, which limited their generalizability.

DISCLOSURES:

The study was supported by AARP and Michigan Medicine and the Department of Veterans Affairs, Veterans Health Administration, and Health Systems Research. One author reported receiving consulting fees and honoraria from various organizations. Details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A brief self-guided online cognitive-behavioral therapy (CBT) intervention was noninferior to comprehensive clinician-guided CBT in reducing symptoms in patients with atopic dermatitis (AD), with both groups showing similar improvements on the Patient-Oriented Eczema Measure (POEM).

METHODOLOGY:

• Researchers conducted a single-blind randomized clinical noninferiority trial at Karolinska Institutet in Stockholm, Sweden, enrolling 168 adults with AD (mean age, 39 years; 84.5% women) from November 2022 to April 2023.
• Participants were randomly assigned to either a 12-week self-guided online CBT intervention (n = 86) without clinician support or a comprehensive 12-week clinician-guided online CBT program (n = 82).
• The primary outcome was the change in POEM score from baseline; reduction of 4 or more points was considered a response, and the predefined noninferiority margin was 3 points.

TAKEAWAY:

• The clinician-guided group improved by 4.20 points on POEM, while the self-guided group improved by 4.60 points, with an estimated mean difference in change of 0.36 points, which was below noninferiority margin.
• Clinicians spent a mean of 36 minutes on treatment guidance and an additional 14 minutes on assessments in the clinician-guided group, whereas they spent only 15.8 minutes on assessments in the self-guided group.
• Both groups demonstrated significant improvements in quality of life, sleep, depressive mood, pruritus, and stress, with no serious adverse events being reported.
• Completion rates were higher in the self-guided group with 81% of participants completing five or more modules, compared with 67% in the clinician-guided group.

IN PRACTICE:

“Overall, the findings support a self-guided intervention as a noninferior and cost-effective alternative to a previously evaluated clinician-guided treatment,” the authors wrote. “Because psychological interventions are rare in dermatological care, this study is an important step toward implementation of CBT for people with AD. The effectiveness of CBT interventions in primary and dermatological specialist care should be investigated.”

SOURCE:

The study was led by Dorian Kern, PhD, Division of Psychology, Karolinska Institutet, and was published online in JAMA Dermatology.

LIMITATIONS: 

High data loss for secondary measurements could affect interpretation of these results. The study relied solely on self-reported measures. The predominance of women participants and the Swedish-language requirement may have limited participation from migrant populations, which could hinder the broader implementation of the study’s findings.

DISCLOSURES:

The study was supported by the Swedish Ministry of Health and Social Affairs. Kern reported receiving grants from the Swedish Ministry of Health and Social Affairs during the conduct of the study. Other authors also reported authorships and royalties, personal fees, grants, or held stocks in DahliaQomit.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A brief self-guided online cognitive-behavioral therapy (CBT) intervention was noninferior to comprehensive clinician-guided CBT in reducing symptoms in patients with atopic dermatitis (AD), with both groups showing similar improvements on the Patient-Oriented Eczema Measure (POEM).

METHODOLOGY:

• Researchers conducted a single-blind randomized clinical noninferiority trial at Karolinska Institutet in Stockholm, Sweden, enrolling 168 adults with AD (mean age, 39 years; 84.5% women) from November 2022 to April 2023.
• Participants were randomly assigned to either a 12-week self-guided online CBT intervention (n = 86) without clinician support or a comprehensive 12-week clinician-guided online CBT program (n = 82).
• The primary outcome was the change in POEM score from baseline; reduction of 4 or more points was considered a response, and the predefined noninferiority margin was 3 points.

TAKEAWAY:

• The clinician-guided group improved by 4.20 points on POEM, while the self-guided group improved by 4.60 points, with an estimated mean difference in change of 0.36 points, which was below noninferiority margin.
• Clinicians spent a mean of 36 minutes on treatment guidance and an additional 14 minutes on assessments in the clinician-guided group, whereas they spent only 15.8 minutes on assessments in the self-guided group.
• Both groups demonstrated significant improvements in quality of life, sleep, depressive mood, pruritus, and stress, with no serious adverse events being reported.
• Completion rates were higher in the self-guided group with 81% of participants completing five or more modules, compared with 67% in the clinician-guided group.

IN PRACTICE:

“Overall, the findings support a self-guided intervention as a noninferior and cost-effective alternative to a previously evaluated clinician-guided treatment,” the authors wrote. “Because psychological interventions are rare in dermatological care, this study is an important step toward implementation of CBT for people with AD. The effectiveness of CBT interventions in primary and dermatological specialist care should be investigated.”

SOURCE:

The study was led by Dorian Kern, PhD, Division of Psychology, Karolinska Institutet, and was published online in JAMA Dermatology.

LIMITATIONS: 

High data loss for secondary measurements could affect interpretation of these results. The study relied solely on self-reported measures. The predominance of women participants and the Swedish-language requirement may have limited participation from migrant populations, which could hinder the broader implementation of the study’s findings.

DISCLOSURES:

The study was supported by the Swedish Ministry of Health and Social Affairs. Kern reported receiving grants from the Swedish Ministry of Health and Social Affairs during the conduct of the study. Other authors also reported authorships and royalties, personal fees, grants, or held stocks in DahliaQomit.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A brief self-guided online cognitive-behavioral therapy (CBT) intervention was noninferior to comprehensive clinician-guided CBT in reducing symptoms in patients with atopic dermatitis (AD), with both groups showing similar improvements on the Patient-Oriented Eczema Measure (POEM).

METHODOLOGY:

• Researchers conducted a single-blind randomized clinical noninferiority trial at Karolinska Institutet in Stockholm, Sweden, enrolling 168 adults with AD (mean age, 39 years; 84.5% women) from November 2022 to April 2023.
• Participants were randomly assigned to either a 12-week self-guided online CBT intervention (n = 86) without clinician support or a comprehensive 12-week clinician-guided online CBT program (n = 82).
• The primary outcome was the change in POEM score from baseline; reduction of 4 or more points was considered a response, and the predefined noninferiority margin was 3 points.

TAKEAWAY:

• The clinician-guided group improved by 4.20 points on POEM, while the self-guided group improved by 4.60 points, with an estimated mean difference in change of 0.36 points, which was below noninferiority margin.
• Clinicians spent a mean of 36 minutes on treatment guidance and an additional 14 minutes on assessments in the clinician-guided group, whereas they spent only 15.8 minutes on assessments in the self-guided group.
• Both groups demonstrated significant improvements in quality of life, sleep, depressive mood, pruritus, and stress, with no serious adverse events being reported.
• Completion rates were higher in the self-guided group with 81% of participants completing five or more modules, compared with 67% in the clinician-guided group.

IN PRACTICE:

“Overall, the findings support a self-guided intervention as a noninferior and cost-effective alternative to a previously evaluated clinician-guided treatment,” the authors wrote. “Because psychological interventions are rare in dermatological care, this study is an important step toward implementation of CBT for people with AD. The effectiveness of CBT interventions in primary and dermatological specialist care should be investigated.”

SOURCE:

The study was led by Dorian Kern, PhD, Division of Psychology, Karolinska Institutet, and was published online in JAMA Dermatology.

LIMITATIONS: 

High data loss for secondary measurements could affect interpretation of these results. The study relied solely on self-reported measures. The predominance of women participants and the Swedish-language requirement may have limited participation from migrant populations, which could hinder the broader implementation of the study’s findings.

DISCLOSURES:

The study was supported by the Swedish Ministry of Health and Social Affairs. Kern reported receiving grants from the Swedish Ministry of Health and Social Affairs during the conduct of the study. Other authors also reported authorships and royalties, personal fees, grants, or held stocks in DahliaQomit.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A survey of dermatologists found that although all respondents receive inpatient central line dressing (CLD)-related consults, most lack standardized protocols for managing adverse skin reactions and reported varying management approaches.

METHODOLOGY:

• Researchers developed and administered a 14-item Qualtrics survey to 107 dermatologists providing pediatric inpatient care through the Society for Pediatric Dermatology’s Inpatient Dermatology Section and Section Chief email lists.
• A total of 35 dermatologists (33%) from multiple institutions responded to the survey; most respondents (94%) specialized in pediatric dermatology.
• Researchers assessed management of CLD-associated adverse skin reactions.

TAKEAWAY:

• All respondents reported receiving CLD-related consults, but 66% indicated there was no personal or institutional standardized approach for managing CLD-associated skin reactions.
• Respondents said most reactions were in children aged 1-12 years (19 or 76% of 25 respondents) compared with those aged < 1 year (3 or 12% of 25 respondents).
• Management strategies included switching to alternative products, applying topical corticosteroids, and performing patch testing for allergies. 

IN PRACTICE:

“Insights derived from this study, including variation in clinician familiarity with reaction patterns, underscore the necessity of a standardized protocol for classifying and managing cutaneous CLD reactions in pediatric patients,” the authors wrote. “Further investigation is needed to better characterize CLD-associated allergic CD [contact dermatitis], irritant CD, and skin infections, as well as at-risk populations, to better inform clinical approaches,” they added.

SOURCE:

The study was led by Carly Mulinda, Columbia University College of Physicians and Surgeons, New York, and was published online on December 16 in Pediatric Dermatology.

LIMITATIONS:

The authors noted variable respondent awareness of institutional CLD and potential recency bias as key limitations of the study.

DISCLOSURES:

Study funding source was not declared. The authors reported no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A survey of dermatologists found that although all respondents receive inpatient central line dressing (CLD)-related consults, most lack standardized protocols for managing adverse skin reactions and reported varying management approaches.

METHODOLOGY:

• Researchers developed and administered a 14-item Qualtrics survey to 107 dermatologists providing pediatric inpatient care through the Society for Pediatric Dermatology’s Inpatient Dermatology Section and Section Chief email lists.
• A total of 35 dermatologists (33%) from multiple institutions responded to the survey; most respondents (94%) specialized in pediatric dermatology.
• Researchers assessed management of CLD-associated adverse skin reactions.

TAKEAWAY:

• All respondents reported receiving CLD-related consults, but 66% indicated there was no personal or institutional standardized approach for managing CLD-associated skin reactions.
• Respondents said most reactions were in children aged 1-12 years (19 or 76% of 25 respondents) compared with those aged < 1 year (3 or 12% of 25 respondents).
• Management strategies included switching to alternative products, applying topical corticosteroids, and performing patch testing for allergies. 

IN PRACTICE:

“Insights derived from this study, including variation in clinician familiarity with reaction patterns, underscore the necessity of a standardized protocol for classifying and managing cutaneous CLD reactions in pediatric patients,” the authors wrote. “Further investigation is needed to better characterize CLD-associated allergic CD [contact dermatitis], irritant CD, and skin infections, as well as at-risk populations, to better inform clinical approaches,” they added.

SOURCE:

The study was led by Carly Mulinda, Columbia University College of Physicians and Surgeons, New York, and was published online on December 16 in Pediatric Dermatology.

LIMITATIONS:

The authors noted variable respondent awareness of institutional CLD and potential recency bias as key limitations of the study.

DISCLOSURES:

Study funding source was not declared. The authors reported no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

A survey of dermatologists found that although all respondents receive inpatient central line dressing (CLD)-related consults, most lack standardized protocols for managing adverse skin reactions and reported varying management approaches.

METHODOLOGY:

• Researchers developed and administered a 14-item Qualtrics survey to 107 dermatologists providing pediatric inpatient care through the Society for Pediatric Dermatology’s Inpatient Dermatology Section and Section Chief email lists.
• A total of 35 dermatologists (33%) from multiple institutions responded to the survey; most respondents (94%) specialized in pediatric dermatology.
• Researchers assessed management of CLD-associated adverse skin reactions.

TAKEAWAY:

• All respondents reported receiving CLD-related consults, but 66% indicated there was no personal or institutional standardized approach for managing CLD-associated skin reactions.
• Respondents said most reactions were in children aged 1-12 years (19 or 76% of 25 respondents) compared with those aged < 1 year (3 or 12% of 25 respondents).
• Management strategies included switching to alternative products, applying topical corticosteroids, and performing patch testing for allergies. 

IN PRACTICE:

“Insights derived from this study, including variation in clinician familiarity with reaction patterns, underscore the necessity of a standardized protocol for classifying and managing cutaneous CLD reactions in pediatric patients,” the authors wrote. “Further investigation is needed to better characterize CLD-associated allergic CD [contact dermatitis], irritant CD, and skin infections, as well as at-risk populations, to better inform clinical approaches,” they added.

SOURCE:

The study was led by Carly Mulinda, Columbia University College of Physicians and Surgeons, New York, and was published online on December 16 in Pediatric Dermatology.

LIMITATIONS:

The authors noted variable respondent awareness of institutional CLD and potential recency bias as key limitations of the study.

DISCLOSURES:

Study funding source was not declared. The authors reported no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A widely accepted assumption in the addiction field is that neuroanatomical changes observed in young people who use alcohol or other substances are largely the consequence of exposure to these substances.

But a new study suggests that neuroanatomical features in children, including greater whole brain and cortical volumes, are evident before exposure to any substances.

The investigators, led by Alex P. Miller, PhD, assistant professor, Department of Psychiatry, Indiana University, Indianapolis, noted that the findings add to a growing body of work that suggests individual brain structure, along with environmental exposure and genetic risk, may influence risk for substance use disorder. 

The findings were published online in JAMA Network Open.

 

Neuroanatomy a Predisposing Risk Factor?

Earlier research showed that substance use is associated with lower gray matter volume, thinner cortex, and less white matter integrity. While it has been widely thought that these changes were induced by the use of alcohol or illicit drugs, recent longitudinal and genetic studies suggest that the neuroanatomical changes may also be predisposing risk factors for substance use.

To better understand the issue, investigators analyzed data on 9804 children (mean baseline age, 9.9 years; 53% men; 76% White) at 22 US sites enrolled in the Adolescent Brain Cognitive Development (ABCD) Study that’s examining brain and behavioral development from middle childhood to young adulthood.

The researchers collected information on the use of alcohol, nicotine, cannabis, and other illicit substances from in-person interviews at baseline and years 1, 2, and 3, as well as interim phone interviews at 6, 18, and 30 months. MRI scans provided extensive brain structural data, including global and regional cortical volume, thickness, surface area, sulcal depth, and subcortical volume.

Of the total, 3460 participants (35%) initiated substance use before age 15, with 90% reporting alcohol use initiation. There was considerable overlap between initiation of alcohol, nicotine, and cannabis.

The researchers tested whether baseline neuroanatomical variability was associated with any substance use initiation before or up to 3 years following initial neuroimaging scans. Study covariates included baseline age, sex, pubertal status, familial relationship (eg, sibling or twin), and prenatal substance exposures. Researchers didn’t control for sociodemographic characteristics as these could influence associations.

 

Significant Brain Differences

Compared with no substance use initiation, any substance use initiation was associated with larger global neuroanatomical indices, including whole brain (beta = 0.05; P = 2.80 × 10^–8), total intracranial (beta = 0.04; P = 3.49 × 10⁻⁶), cortical (beta = 0.05; P = 4.31 × 10^–8), and subcortical volumes (beta = 0.05; P = 4.39 × 10^–8), as well as greater total cortical surface area (beta = 0.04; P = 6.05 × 10^–7).

The direction of associations between cortical thickness and substance use initiation was regionally specific; any substance use initiation was characterized by thinner cortex in all frontal regions (eg, rostral middle frontal gyrus, beta = −0.03; P = 6.99 × 10^–6), but thicker cortex in all other lobes. It was also associated with larger regional brain volumes, deeper regional sulci, and differences in regional cortical surface area.

The authors noted total cortical thickness peaks at age 1.7 years and steadily declines throughout life. By contrast, subcortical volumes peak at 14.4 years of age and generally remain stable before steep later life declines.

Secondary analyses compared initiation of the three most commonly used substances in early adolescence (alcohol, nicotine, and cannabis) with no substance use.

Findings for alcohol largely mirrored those for any substance use. However, the study uncovered additional significant associations, including greater left lateral occipital volume and bilateral para-hippocampal gyri cortical thickness and less bilateral superior frontal gyri cortical thickness.

Nicotine use was associated with lower right superior frontal gyrus volume and deeper left lateral orbitofrontal cortex sulci. And cannabis use was associated with thinner left precentral gyrus and lower right inferior parietal gyrus and right caudate volumes.

The authors noted results for nicotine and cannabis may not have had adequate statistical power, and small effects suggest these findings aren’t clinically informative for individuals. However, they wrote, “They do inform and challenge current theoretical models of addiction.”

 

Associations Precede Substance Use

A post hoc analysis further challenges current models of addiction. When researchers looked only at the 1203 youth who initiated substance use after the baseline neuroimaging session, they found most associations preceded substance use.

“That regional associations may precede substance use initiation, including less cortical thickness in the right rostral middle frontal gyrus, challenges predominant interpretations that these associations arise largely due to neurotoxic consequences of exposure and increases the plausibility that these features may, at least partially, reflect markers of predispositional risk,” wrote the authors.

A study limitation was that unmeasured confounders and undetected systemic differences in missing data may have influenced associations. Sociodemographic, environmental, and genetic variables that were not included as covariates are likely associated with both neuroanatomical variability and substance use initiation and may moderate associations between them, said the authors.

The ABCD Study provides “a robust and large database of longitudinal data” that goes beyond previous neuroimaging research “to understand the bidirectional relationship between brain structure and substance use,” Miller said in a press release.

“The hope is that these types of studies, in conjunction with other data on environmental exposures and genetic risk, could help change how we think about the development of substance use disorders and inform more accurate models of addiction moving forward,” Miller said.

 

Reevaluating Causal Assumptions

In an accompanying editorial, Felix Pichardo, MA, and Sylia Wilson, PhD, from the Institute of Child Development, University of Minnesota, Minneapolis, suggested that it may be time to “reevaluate the causal assumptions that underlie brain disease models of addiction” and the mechanisms by which it develops, persists, and becomes harmful.

Neurotoxic effects of substances are central to current brain disease models of addiction, wrote Pichardo and Wilson. “Substance exposure is thought to affect cortical and subcortical regions that support interrelated systems, resulting in desensitization of reward-related processing, increased stress that prompts cravings, negative emotions when cravings are unsated, and weakening of cognitive control abilities that leads to repeated returns to use.”

The editorial writers praised the ABCD Study for its large sample size for providing a level of precision, statistical accuracy, and ability to identify both larger and smaller effects, which are critical for addiction research.

Unlike most addiction research that relies on cross-sectional designs, the current study used longitudinal assessments, which is another of its strengths, they noted.

“Longitudinal study designs like in the ABCD Study are fundamental for establishing temporal ordering across constructs, which is important because establishing temporal precedence is a key step in determining causal links and underlying mechanisms.”

The inclusion of several genetically informative components, such as the family study design, nested twin subsamples, and DNA collection, “allows researchers to extend beyond temporal precedence toward increased causal inference and identification of mechanisms,” they added.

The study received support from the National Institutes of Health. The study authors and editorial writers had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

A widely accepted assumption in the addiction field is that neuroanatomical changes observed in young people who use alcohol or other substances are largely the consequence of exposure to these substances.

But a new study suggests that neuroanatomical features in children, including greater whole brain and cortical volumes, are evident before exposure to any substances.

The investigators, led by Alex P. Miller, PhD, assistant professor, Department of Psychiatry, Indiana University, Indianapolis, noted that the findings add to a growing body of work that suggests individual brain structure, along with environmental exposure and genetic risk, may influence risk for substance use disorder. 

The findings were published online in JAMA Network Open.

 

Neuroanatomy a Predisposing Risk Factor?

Earlier research showed that substance use is associated with lower gray matter volume, thinner cortex, and less white matter integrity. While it has been widely thought that these changes were induced by the use of alcohol or illicit drugs, recent longitudinal and genetic studies suggest that the neuroanatomical changes may also be predisposing risk factors for substance use.

To better understand the issue, investigators analyzed data on 9804 children (mean baseline age, 9.9 years; 53% men; 76% White) at 22 US sites enrolled in the Adolescent Brain Cognitive Development (ABCD) Study that’s examining brain and behavioral development from middle childhood to young adulthood.

The researchers collected information on the use of alcohol, nicotine, cannabis, and other illicit substances from in-person interviews at baseline and years 1, 2, and 3, as well as interim phone interviews at 6, 18, and 30 months. MRI scans provided extensive brain structural data, including global and regional cortical volume, thickness, surface area, sulcal depth, and subcortical volume.

Of the total, 3460 participants (35%) initiated substance use before age 15, with 90% reporting alcohol use initiation. There was considerable overlap between initiation of alcohol, nicotine, and cannabis.

The researchers tested whether baseline neuroanatomical variability was associated with any substance use initiation before or up to 3 years following initial neuroimaging scans. Study covariates included baseline age, sex, pubertal status, familial relationship (eg, sibling or twin), and prenatal substance exposures. Researchers didn’t control for sociodemographic characteristics as these could influence associations.

 

Significant Brain Differences

Compared with no substance use initiation, any substance use initiation was associated with larger global neuroanatomical indices, including whole brain (beta = 0.05; P = 2.80 × 10^–8), total intracranial (beta = 0.04; P = 3.49 × 10⁻⁶), cortical (beta = 0.05; P = 4.31 × 10^–8), and subcortical volumes (beta = 0.05; P = 4.39 × 10^–8), as well as greater total cortical surface area (beta = 0.04; P = 6.05 × 10^–7).

The direction of associations between cortical thickness and substance use initiation was regionally specific; any substance use initiation was characterized by thinner cortex in all frontal regions (eg, rostral middle frontal gyrus, beta = −0.03; P = 6.99 × 10^–6), but thicker cortex in all other lobes. It was also associated with larger regional brain volumes, deeper regional sulci, and differences in regional cortical surface area.

The authors noted total cortical thickness peaks at age 1.7 years and steadily declines throughout life. By contrast, subcortical volumes peak at 14.4 years of age and generally remain stable before steep later life declines.

Secondary analyses compared initiation of the three most commonly used substances in early adolescence (alcohol, nicotine, and cannabis) with no substance use.

Findings for alcohol largely mirrored those for any substance use. However, the study uncovered additional significant associations, including greater left lateral occipital volume and bilateral para-hippocampal gyri cortical thickness and less bilateral superior frontal gyri cortical thickness.

Nicotine use was associated with lower right superior frontal gyrus volume and deeper left lateral orbitofrontal cortex sulci. And cannabis use was associated with thinner left precentral gyrus and lower right inferior parietal gyrus and right caudate volumes.

The authors noted results for nicotine and cannabis may not have had adequate statistical power, and small effects suggest these findings aren’t clinically informative for individuals. However, they wrote, “They do inform and challenge current theoretical models of addiction.”

 

Associations Precede Substance Use

A post hoc analysis further challenges current models of addiction. When researchers looked only at the 1203 youth who initiated substance use after the baseline neuroimaging session, they found most associations preceded substance use.

“That regional associations may precede substance use initiation, including less cortical thickness in the right rostral middle frontal gyrus, challenges predominant interpretations that these associations arise largely due to neurotoxic consequences of exposure and increases the plausibility that these features may, at least partially, reflect markers of predispositional risk,” wrote the authors.

A study limitation was that unmeasured confounders and undetected systemic differences in missing data may have influenced associations. Sociodemographic, environmental, and genetic variables that were not included as covariates are likely associated with both neuroanatomical variability and substance use initiation and may moderate associations between them, said the authors.

The ABCD Study provides “a robust and large database of longitudinal data” that goes beyond previous neuroimaging research “to understand the bidirectional relationship between brain structure and substance use,” Miller said in a press release.

“The hope is that these types of studies, in conjunction with other data on environmental exposures and genetic risk, could help change how we think about the development of substance use disorders and inform more accurate models of addiction moving forward,” Miller said.

 

Reevaluating Causal Assumptions

In an accompanying editorial, Felix Pichardo, MA, and Sylia Wilson, PhD, from the Institute of Child Development, University of Minnesota, Minneapolis, suggested that it may be time to “reevaluate the causal assumptions that underlie brain disease models of addiction” and the mechanisms by which it develops, persists, and becomes harmful.

Neurotoxic effects of substances are central to current brain disease models of addiction, wrote Pichardo and Wilson. “Substance exposure is thought to affect cortical and subcortical regions that support interrelated systems, resulting in desensitization of reward-related processing, increased stress that prompts cravings, negative emotions when cravings are unsated, and weakening of cognitive control abilities that leads to repeated returns to use.”

The editorial writers praised the ABCD Study for its large sample size for providing a level of precision, statistical accuracy, and ability to identify both larger and smaller effects, which are critical for addiction research.

Unlike most addiction research that relies on cross-sectional designs, the current study used longitudinal assessments, which is another of its strengths, they noted.

“Longitudinal study designs like in the ABCD Study are fundamental for establishing temporal ordering across constructs, which is important because establishing temporal precedence is a key step in determining causal links and underlying mechanisms.”

The inclusion of several genetically informative components, such as the family study design, nested twin subsamples, and DNA collection, “allows researchers to extend beyond temporal precedence toward increased causal inference and identification of mechanisms,” they added.

The study received support from the National Institutes of Health. The study authors and editorial writers had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

A widely accepted assumption in the addiction field is that neuroanatomical changes observed in young people who use alcohol or other substances are largely the consequence of exposure to these substances.

But a new study suggests that neuroanatomical features in children, including greater whole brain and cortical volumes, are evident before exposure to any substances.

The investigators, led by Alex P. Miller, PhD, assistant professor, Department of Psychiatry, Indiana University, Indianapolis, noted that the findings add to a growing body of work that suggests individual brain structure, along with environmental exposure and genetic risk, may influence risk for substance use disorder. 

The findings were published online in JAMA Network Open.

 

Neuroanatomy a Predisposing Risk Factor?

Earlier research showed that substance use is associated with lower gray matter volume, thinner cortex, and less white matter integrity. While it has been widely thought that these changes were induced by the use of alcohol or illicit drugs, recent longitudinal and genetic studies suggest that the neuroanatomical changes may also be predisposing risk factors for substance use.

To better understand the issue, investigators analyzed data on 9804 children (mean baseline age, 9.9 years; 53% men; 76% White) at 22 US sites enrolled in the Adolescent Brain Cognitive Development (ABCD) Study that’s examining brain and behavioral development from middle childhood to young adulthood.

The researchers collected information on the use of alcohol, nicotine, cannabis, and other illicit substances from in-person interviews at baseline and years 1, 2, and 3, as well as interim phone interviews at 6, 18, and 30 months. MRI scans provided extensive brain structural data, including global and regional cortical volume, thickness, surface area, sulcal depth, and subcortical volume.

Of the total, 3460 participants (35%) initiated substance use before age 15, with 90% reporting alcohol use initiation. There was considerable overlap between initiation of alcohol, nicotine, and cannabis.

The researchers tested whether baseline neuroanatomical variability was associated with any substance use initiation before or up to 3 years following initial neuroimaging scans. Study covariates included baseline age, sex, pubertal status, familial relationship (eg, sibling or twin), and prenatal substance exposures. Researchers didn’t control for sociodemographic characteristics as these could influence associations.

 

Significant Brain Differences

Compared with no substance use initiation, any substance use initiation was associated with larger global neuroanatomical indices, including whole brain (beta = 0.05; P = 2.80 × 10^–8), total intracranial (beta = 0.04; P = 3.49 × 10⁻⁶), cortical (beta = 0.05; P = 4.31 × 10^–8), and subcortical volumes (beta = 0.05; P = 4.39 × 10^–8), as well as greater total cortical surface area (beta = 0.04; P = 6.05 × 10^–7).

The direction of associations between cortical thickness and substance use initiation was regionally specific; any substance use initiation was characterized by thinner cortex in all frontal regions (eg, rostral middle frontal gyrus, beta = −0.03; P = 6.99 × 10^–6), but thicker cortex in all other lobes. It was also associated with larger regional brain volumes, deeper regional sulci, and differences in regional cortical surface area.

The authors noted total cortical thickness peaks at age 1.7 years and steadily declines throughout life. By contrast, subcortical volumes peak at 14.4 years of age and generally remain stable before steep later life declines.

Secondary analyses compared initiation of the three most commonly used substances in early adolescence (alcohol, nicotine, and cannabis) with no substance use.

Findings for alcohol largely mirrored those for any substance use. However, the study uncovered additional significant associations, including greater left lateral occipital volume and bilateral para-hippocampal gyri cortical thickness and less bilateral superior frontal gyri cortical thickness.

Nicotine use was associated with lower right superior frontal gyrus volume and deeper left lateral orbitofrontal cortex sulci. And cannabis use was associated with thinner left precentral gyrus and lower right inferior parietal gyrus and right caudate volumes.

The authors noted results for nicotine and cannabis may not have had adequate statistical power, and small effects suggest these findings aren’t clinically informative for individuals. However, they wrote, “They do inform and challenge current theoretical models of addiction.”

 

Associations Precede Substance Use

A post hoc analysis further challenges current models of addiction. When researchers looked only at the 1203 youth who initiated substance use after the baseline neuroimaging session, they found most associations preceded substance use.

“That regional associations may precede substance use initiation, including less cortical thickness in the right rostral middle frontal gyrus, challenges predominant interpretations that these associations arise largely due to neurotoxic consequences of exposure and increases the plausibility that these features may, at least partially, reflect markers of predispositional risk,” wrote the authors.

A study limitation was that unmeasured confounders and undetected systemic differences in missing data may have influenced associations. Sociodemographic, environmental, and genetic variables that were not included as covariates are likely associated with both neuroanatomical variability and substance use initiation and may moderate associations between them, said the authors.

The ABCD Study provides “a robust and large database of longitudinal data” that goes beyond previous neuroimaging research “to understand the bidirectional relationship between brain structure and substance use,” Miller said in a press release.

“The hope is that these types of studies, in conjunction with other data on environmental exposures and genetic risk, could help change how we think about the development of substance use disorders and inform more accurate models of addiction moving forward,” Miller said.

 

Reevaluating Causal Assumptions

In an accompanying editorial, Felix Pichardo, MA, and Sylia Wilson, PhD, from the Institute of Child Development, University of Minnesota, Minneapolis, suggested that it may be time to “reevaluate the causal assumptions that underlie brain disease models of addiction” and the mechanisms by which it develops, persists, and becomes harmful.

Neurotoxic effects of substances are central to current brain disease models of addiction, wrote Pichardo and Wilson. “Substance exposure is thought to affect cortical and subcortical regions that support interrelated systems, resulting in desensitization of reward-related processing, increased stress that prompts cravings, negative emotions when cravings are unsated, and weakening of cognitive control abilities that leads to repeated returns to use.”

The editorial writers praised the ABCD Study for its large sample size for providing a level of precision, statistical accuracy, and ability to identify both larger and smaller effects, which are critical for addiction research.

Unlike most addiction research that relies on cross-sectional designs, the current study used longitudinal assessments, which is another of its strengths, they noted.

“Longitudinal study designs like in the ABCD Study are fundamental for establishing temporal ordering across constructs, which is important because establishing temporal precedence is a key step in determining causal links and underlying mechanisms.”

The inclusion of several genetically informative components, such as the family study design, nested twin subsamples, and DNA collection, “allows researchers to extend beyond temporal precedence toward increased causal inference and identification of mechanisms,” they added.

The study received support from the National Institutes of Health. The study authors and editorial writers had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

What current events are keeping Americans up at night? The economy, gun violence, and hate crimes top the list, results from a newly released American Psychiatric Association (APA) survey showed.

Anxiety about international conflicts — namely, the Russia-Ukraine and Israel-Hamas wars — also remains high.

“While we like to stay informed, the news can also impact our mental health, and being mindful of that impact is important. If current events seem overwhelming it may be time to limit your news consumption,” APA CEO and Medical Director Marketa M. Wills, MD, MBD, said in a statement.

Survey results also revealed the election and the holidays were common sources of stress.

“Election stress is common, and it’s important to recognize that, as we’re spending more time with family around the holidays, we might need to have a strategy to manage our own mental health during these times,” Howard Liu, MD, MBA, chair of the Department of Psychiatry, University of Nebraska Medical Center, Omaha, told this news organization.

“As with any difficult topic, we all have different levels of avoidance or desire to engage, and it’s okay to set boundaries based on past conversations with family. I think sometimes we get drawn into arguments that we don’t want to have or may not be productive for either side,” said Liu, who chairs the APA Council on Communications.

In line with trends throughout 2024, adults polled by the APA in November were most anxious about the economy (75%), gun violence (64%), and hate crimes (60%). The survey included 2200 US adults as part of the APA’s Healthy Minds monthly series.

Anxiety about international conflicts remained high in November at 57% — but was down from 65% in August.

Election anxiety remained high in mid-November but not as high as before the election. In August, 72% of Americans said they were anxious about the 2024 election. In November, just after the election, 50% reported anxiety over the election outcome.

“I think the anticipation of change can sometimes be worse than the change itself. So I think a lot of people are now taking the attitude of — let’s wait and see what actually happens,” said Liu.

Half the adults (50%) anticipate the same amount of stress as the 2023 holiday season, while almost one third expect more stress (28%), and one fourth anticipate less stress (23%).

When asked how the holidays generally affect their mental health, 38% said it has positive effects, and 21% said the opposite was true.

 

Anxiety About the Future

After a divisive election, most Americans were ready to avoid politics at holiday gatherings, results of a separate poll conducted by the American Psychological Association in late November showed.

That poll, which included 2000 US adults, showed that more than 7 in 10 (72%) said they wanted to avoid talking about politics with family and friends over the holidays.

In addition, nearly two in five adults (39%) reported they were stressed by the thought of politics being raised at holiday gatherings and would try to avoid family members they disagree with. Younger adults were significantly more likely than were their older counterparts to report they planned to avoid family over the holidays.

The future of the nation also weighs on the minds of many Americans.

Another poll conducted by the American Psychological Association in August prior to the 2024 US presidential election showed that 77% of respondents said the future of the nation was a significant source of stress for them.

In the postelection poll, more than one third of adults (35%) said they are more stressed about the future of the nation now than they were leading up to the election, and another third reported they are now less stressed (32%). A quarter of adults (24%) said their stress about the future of the nation was unchanged, and 9% said they were not stressed about the future of the nation then or now.

“There’s still clearly a lot of uncertainty, and there’s a lot of activity right now for the president-elect,” which can contribute to anxiety, C. Vaile Wright, PhD, psychologist, researcher and spokesperson for the American Psychological Association, told this news organization.

These data also show that many Americans have little or no trust in the government, with some wanting to leave the United States.

“It’s a reflection of the lack of strong leadership across the board in this country. We have a governmental system in place that does not seem to serve the people, but to serve corporations and maintenance of power. I think people are disillusioned with it and that creates a lack of trust and hopelessness,” Wright noted.

Liu and Wright reported no relevant disclosures.

A version of this article appeared on Medscape.com.

What current events are keeping Americans up at night? The economy, gun violence, and hate crimes top the list, results from a newly released American Psychiatric Association (APA) survey showed.

Anxiety about international conflicts — namely, the Russia-Ukraine and Israel-Hamas wars — also remains high.

“While we like to stay informed, the news can also impact our mental health, and being mindful of that impact is important. If current events seem overwhelming it may be time to limit your news consumption,” APA CEO and Medical Director Marketa M. Wills, MD, MBD, said in a statement.

Survey results also revealed the election and the holidays were common sources of stress.

“Election stress is common, and it’s important to recognize that, as we’re spending more time with family around the holidays, we might need to have a strategy to manage our own mental health during these times,” Howard Liu, MD, MBA, chair of the Department of Psychiatry, University of Nebraska Medical Center, Omaha, told this news organization.

“As with any difficult topic, we all have different levels of avoidance or desire to engage, and it’s okay to set boundaries based on past conversations with family. I think sometimes we get drawn into arguments that we don’t want to have or may not be productive for either side,” said Liu, who chairs the APA Council on Communications.

In line with trends throughout 2024, adults polled by the APA in November were most anxious about the economy (75%), gun violence (64%), and hate crimes (60%). The survey included 2200 US adults as part of the APA’s Healthy Minds monthly series.

Anxiety about international conflicts remained high in November at 57% — but was down from 65% in August.

Election anxiety remained high in mid-November but not as high as before the election. In August, 72% of Americans said they were anxious about the 2024 election. In November, just after the election, 50% reported anxiety over the election outcome.

“I think the anticipation of change can sometimes be worse than the change itself. So I think a lot of people are now taking the attitude of — let’s wait and see what actually happens,” said Liu.

Half the adults (50%) anticipate the same amount of stress as the 2023 holiday season, while almost one third expect more stress (28%), and one fourth anticipate less stress (23%).

When asked how the holidays generally affect their mental health, 38% said it has positive effects, and 21% said the opposite was true.

 

Anxiety About the Future

After a divisive election, most Americans were ready to avoid politics at holiday gatherings, results of a separate poll conducted by the American Psychological Association in late November showed.

That poll, which included 2000 US adults, showed that more than 7 in 10 (72%) said they wanted to avoid talking about politics with family and friends over the holidays.

In addition, nearly two in five adults (39%) reported they were stressed by the thought of politics being raised at holiday gatherings and would try to avoid family members they disagree with. Younger adults were significantly more likely than were their older counterparts to report they planned to avoid family over the holidays.

The future of the nation also weighs on the minds of many Americans.

Another poll conducted by the American Psychological Association in August prior to the 2024 US presidential election showed that 77% of respondents said the future of the nation was a significant source of stress for them.

In the postelection poll, more than one third of adults (35%) said they are more stressed about the future of the nation now than they were leading up to the election, and another third reported they are now less stressed (32%). A quarter of adults (24%) said their stress about the future of the nation was unchanged, and 9% said they were not stressed about the future of the nation then or now.

“There’s still clearly a lot of uncertainty, and there’s a lot of activity right now for the president-elect,” which can contribute to anxiety, C. Vaile Wright, PhD, psychologist, researcher and spokesperson for the American Psychological Association, told this news organization.

These data also show that many Americans have little or no trust in the government, with some wanting to leave the United States.

“It’s a reflection of the lack of strong leadership across the board in this country. We have a governmental system in place that does not seem to serve the people, but to serve corporations and maintenance of power. I think people are disillusioned with it and that creates a lack of trust and hopelessness,” Wright noted.

Liu and Wright reported no relevant disclosures.

A version of this article appeared on Medscape.com.

What current events are keeping Americans up at night? The economy, gun violence, and hate crimes top the list, results from a newly released American Psychiatric Association (APA) survey showed.

Anxiety about international conflicts — namely, the Russia-Ukraine and Israel-Hamas wars — also remains high.

“While we like to stay informed, the news can also impact our mental health, and being mindful of that impact is important. If current events seem overwhelming it may be time to limit your news consumption,” APA CEO and Medical Director Marketa M. Wills, MD, MBD, said in a statement.

Survey results also revealed the election and the holidays were common sources of stress.

“Election stress is common, and it’s important to recognize that, as we’re spending more time with family around the holidays, we might need to have a strategy to manage our own mental health during these times,” Howard Liu, MD, MBA, chair of the Department of Psychiatry, University of Nebraska Medical Center, Omaha, told this news organization.

“As with any difficult topic, we all have different levels of avoidance or desire to engage, and it’s okay to set boundaries based on past conversations with family. I think sometimes we get drawn into arguments that we don’t want to have or may not be productive for either side,” said Liu, who chairs the APA Council on Communications.

In line with trends throughout 2024, adults polled by the APA in November were most anxious about the economy (75%), gun violence (64%), and hate crimes (60%). The survey included 2200 US adults as part of the APA’s Healthy Minds monthly series.

Anxiety about international conflicts remained high in November at 57% — but was down from 65% in August.

Election anxiety remained high in mid-November but not as high as before the election. In August, 72% of Americans said they were anxious about the 2024 election. In November, just after the election, 50% reported anxiety over the election outcome.

“I think the anticipation of change can sometimes be worse than the change itself. So I think a lot of people are now taking the attitude of — let’s wait and see what actually happens,” said Liu.

Half the adults (50%) anticipate the same amount of stress as the 2023 holiday season, while almost one third expect more stress (28%), and one fourth anticipate less stress (23%).

When asked how the holidays generally affect their mental health, 38% said it has positive effects, and 21% said the opposite was true.

 

Anxiety About the Future

After a divisive election, most Americans were ready to avoid politics at holiday gatherings, results of a separate poll conducted by the American Psychological Association in late November showed.

That poll, which included 2000 US adults, showed that more than 7 in 10 (72%) said they wanted to avoid talking about politics with family and friends over the holidays.

In addition, nearly two in five adults (39%) reported they were stressed by the thought of politics being raised at holiday gatherings and would try to avoid family members they disagree with. Younger adults were significantly more likely than were their older counterparts to report they planned to avoid family over the holidays.

The future of the nation also weighs on the minds of many Americans.

Another poll conducted by the American Psychological Association in August prior to the 2024 US presidential election showed that 77% of respondents said the future of the nation was a significant source of stress for them.

In the postelection poll, more than one third of adults (35%) said they are more stressed about the future of the nation now than they were leading up to the election, and another third reported they are now less stressed (32%). A quarter of adults (24%) said their stress about the future of the nation was unchanged, and 9% said they were not stressed about the future of the nation then or now.

“There’s still clearly a lot of uncertainty, and there’s a lot of activity right now for the president-elect,” which can contribute to anxiety, C. Vaile Wright, PhD, psychologist, researcher and spokesperson for the American Psychological Association, told this news organization.

These data also show that many Americans have little or no trust in the government, with some wanting to leave the United States.

“It’s a reflection of the lack of strong leadership across the board in this country. We have a governmental system in place that does not seem to serve the people, but to serve corporations and maintenance of power. I think people are disillusioned with it and that creates a lack of trust and hopelessness,” Wright noted.

Liu and Wright reported no relevant disclosures.

A version of this article appeared on Medscape.com.

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

A version of this article first appeared on Medscape.com.

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

A version of this article first appeared on Medscape.com.

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

A version of this article first appeared on Medscape.com.

A drug that combines the atypical antipsychotic brexpiprazole and the selective serotonin reuptake inhibitor sertraline provides significantly greater relief of posttraumatic stress disorder (PTSD) symptoms than sertraline plus placebo, results of a phase 3 trial showed.

The medication is currently under review by the Food and Drug Administration (FDA) and if approved, will be the first pharmacologic option for PTSD in more than 20 years.

The trial met its primary endpoint of change in the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) (CAPS-5) total score at week 10 and secondary patient-reported outcomes of PTSD symptoms, anxiety, and depression.

“And what is really cool, what’s really impactful is the combination worked better than sertraline plus placebo on a brief inventory of psychosocial functioning,” study investigator Lori L. Davis, a senior research psychiatrist, Birmingham Veterans Affairs Health Care System in Alabama, said in an interview.

“We can treat symptoms but that’s where the rubber meets the road, in terms of are they functioning better,” added Davis, who is also an adjunct professor of psychiatry, Heersink School of Medicine, University of Alabama at Birmingham.

The findings were published online on December 18 in JAMA Psychiatry and reported in May 2024 as part of a trio of trials conducted by Otsuka Pharmaceutical and Lundbeck Pharmaceuticals, codevelopers of the drug.

 

Clinically Meaningful

The FDA accepted the companies’ supplemental new drug application in June with a decision on approval expected in early February 2025.

“This study provides promising results for a medication that may be an important new option for PTSD,” John Krystal, MD, director, Clinical Neuroscience Division, National Center for PTSD, US Department of Veterans Affairs, who was not involved in the research, said in an interview. “New PTSD treatments are a high priority.”

Currently, there are two FDA-approved medication treatments for PTSD — sertraline and paroxetine.

“They are helpful for many people, but patients are often left with residual symptoms or tolerability issues,” noted Krystal, who is also professor and chair of psychiatry, Yale University, New Haven, Connecticut.

“New medications that might address the important ‘effectiveness gap’ in PTSD could help to reduce the remaining distress, disability, and suicide risk associated with PTSD.” 

The double-blind, phase 3 trial included 416 adults aged 18-65 years with a DSM-5 diagnosis of PTSD and symptoms for at least 6 months prior to screening. Patients underwent a 1-week placebo-run in period followed by randomization to daily oral brexpiprazole 2-3 mg plus sertraline 150 mg or daily sertraline 150 mg plus placebo for 11 weeks.

Participants’ mean age was 37.4 years, 74.5% were women, and mean CAPS-5 total score was 38.4, suggesting moderate to high severity PTSD, Davis said. The average time from the index traumatic event was 4 years and three fourths had no prior exposure to PTSD prescription medications.

At week 10, the mean change in CAPS-5 score from randomization was –19.2 points in the brexpiprazole plus sertraline group and –13.6 points in the sertraline plus placebo group (95% CI, –8.79 to –2.38; P < .001).

Asked whether the 5.59-point treatment difference is clinically meaningful, Davis said there is no widely agreed definition for change in CAPS-5 total score but that a within-group reduction of more than 10-13 points is most-often cited as being clinically meaningful.

The key secondary endpoint of least square mean change in the patient-reported Brief Inventory of Psychosocial Function total score from baseline to week 12 was –33.8 with the combination vs –21.8 with sertraline plus placebo (95% CI, –19.4 to –4.62; P = .002).

“That’s clinically meaningful for me as a provider and a clinician and a researcher when you’re getting the PTSD symptom change differences in parallel with the improvement in functional outcome,” she said. “I see that as the clinically meaningful gauge.”

In terms of safety, 3.9% of the participants in the brexpiprazole/sertraline group and 10.2% of those in the sertraline/placebo group discontinued treatment because of adverse events.

In both the combination and control groups, the only treatment-emergent adverse event with an incidence of more than 10% was nausea (12.2% vs 11.7%, respectively).

At the last visit, the mean change in body weight from baseline was an increase of 1.3 kg for brexpiprazole plus sertraline vs 0 kg for sertraline alone. Rates of fatigue (6.8% vs 4.1%) and somnolence (5.4% vs 2.6%) were also higher with brexpiprazole plus sertraline.

 

A Trio of Clinical Trials

The findings are part of a larger program reported by the drug makers that includes a flexible-dose brexpiprazole phase 2 trial that met the same CAPS-5 primary endpoint and a second phase 3 trial (072 study) that did not.

“We’ve looked at that data and the sertraline/placebo response was a lot higher, so it was not due to a lack of response with the combination but due to a more robust response with the active control,” Davis said. “But we want to point out for that 072 study, there was still important separation between the combination and sertraline plus placebo on the functional outcome.”

All three trials ran for 12 weeks, so longer-term efficacy and safety data are needed, she said. Other limitations of the published phase 3 study are the patient eligibility criteria, restrictions on concomitant therapy, and lack of non-US sites, which many limit generalizability, the authors noted.

“Specifically, the exclusion of patients with a current major depressive episode is both a strength (to show a specific effect on PTSD) and a limitation (given the high prevalence of comorbid depression in PTSD),” they added.

 

Kudos, Caveats

Reached for comment, Vincent F. Capaldi, II, MD, ScM, professor and chair, department of psychiatry, Uniformed Services University of the Health Sciences School of Medicine, Bethesda, Maryland, said the exclusion of these patients is a limitation but that the study was well designed and conducted in a large sample across the United States.

“The findings suggest that brexpiprazole plus sertraline is a more effective treatment for PTSD than sertraline alone,” he said. “This finding is significant for our service members, who suffer from PTSD at higher rates than the general population.”

Additionally, the significant improvement in psychosocial functioning at week 12 “is important because PTSD is known to cause significant social and occupational disability, as well as quality-of-life issues,” he said.

Capaldi pointed out, however, that the study was conducted only at US sites and did not specifically target military/veteran persons, which may limit applicability to these unique populations.

“While subgroup analyses were generally consistent with the primary analysis, the study was not powered to detect differences between subgroups,” he added. “These subgroup analyses are quite important when considering military and veteran populations.”

Further research is needed to explore whether certain traumas are more responsive to combination treatment, the efficacy of augmenting existing sertraline therapy, and the specific mechanisms of brexpiprazole driving the improved outcomes, Capaldi said.

This study was funded by Otsuka Pharmaceutical Development & Commercialization, which was involved in the design, conduct, and data analysis. Davis reported receiving advisory board fees from Otsuka and Boehringer Ingelheim; lecture fees from Clinical Care Options; and grants from Alkermes, the Veterans Affairs, Patient-Centered Outcomes Research Institute, Department of Defense, and Social Finance. Several coauthors are employees of Otsuka. Krystal reported serving as a consultant for Otsuka America Pharmaceutical, Aptinyx, Biogen, IDEC, Bionomics, Boehringer Ingelheim International, Clearmind Medicine, Cybin IRL, Enveric Biosciences, Epiodyne, EpiVario, Janssen, Jazz Pharmaceuticals, Perception Neuroscience, Praxis Precision Medicines, Springcare, and Sunovion Pharmaceuticals. Krystal also reported serving as a scientific advisory board member for several companies and holding several patents.

A version of this article appeared on Medscape.com.

A drug that combines the atypical antipsychotic brexpiprazole and the selective serotonin reuptake inhibitor sertraline provides significantly greater relief of posttraumatic stress disorder (PTSD) symptoms than sertraline plus placebo, results of a phase 3 trial showed.

The medication is currently under review by the Food and Drug Administration (FDA) and if approved, will be the first pharmacologic option for PTSD in more than 20 years.

The trial met its primary endpoint of change in the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) (CAPS-5) total score at week 10 and secondary patient-reported outcomes of PTSD symptoms, anxiety, and depression.

“And what is really cool, what’s really impactful is the combination worked better than sertraline plus placebo on a brief inventory of psychosocial functioning,” study investigator Lori L. Davis, a senior research psychiatrist, Birmingham Veterans Affairs Health Care System in Alabama, said in an interview.

“We can treat symptoms but that’s where the rubber meets the road, in terms of are they functioning better,” added Davis, who is also an adjunct professor of psychiatry, Heersink School of Medicine, University of Alabama at Birmingham.

The findings were published online on December 18 in JAMA Psychiatry and reported in May 2024 as part of a trio of trials conducted by Otsuka Pharmaceutical and Lundbeck Pharmaceuticals, codevelopers of the drug.

 

Clinically Meaningful

The FDA accepted the companies’ supplemental new drug application in June with a decision on approval expected in early February 2025.

“This study provides promising results for a medication that may be an important new option for PTSD,” John Krystal, MD, director, Clinical Neuroscience Division, National Center for PTSD, US Department of Veterans Affairs, who was not involved in the research, said in an interview. “New PTSD treatments are a high priority.”

Currently, there are two FDA-approved medication treatments for PTSD — sertraline and paroxetine.

“They are helpful for many people, but patients are often left with residual symptoms or tolerability issues,” noted Krystal, who is also professor and chair of psychiatry, Yale University, New Haven, Connecticut.

“New medications that might address the important ‘effectiveness gap’ in PTSD could help to reduce the remaining distress, disability, and suicide risk associated with PTSD.” 

The double-blind, phase 3 trial included 416 adults aged 18-65 years with a DSM-5 diagnosis of PTSD and symptoms for at least 6 months prior to screening. Patients underwent a 1-week placebo-run in period followed by randomization to daily oral brexpiprazole 2-3 mg plus sertraline 150 mg or daily sertraline 150 mg plus placebo for 11 weeks.

Participants’ mean age was 37.4 years, 74.5% were women, and mean CAPS-5 total score was 38.4, suggesting moderate to high severity PTSD, Davis said. The average time from the index traumatic event was 4 years and three fourths had no prior exposure to PTSD prescription medications.

At week 10, the mean change in CAPS-5 score from randomization was –19.2 points in the brexpiprazole plus sertraline group and –13.6 points in the sertraline plus placebo group (95% CI, –8.79 to –2.38; P < .001).

Asked whether the 5.59-point treatment difference is clinically meaningful, Davis said there is no widely agreed definition for change in CAPS-5 total score but that a within-group reduction of more than 10-13 points is most-often cited as being clinically meaningful.

The key secondary endpoint of least square mean change in the patient-reported Brief Inventory of Psychosocial Function total score from baseline to week 12 was –33.8 with the combination vs –21.8 with sertraline plus placebo (95% CI, –19.4 to –4.62; P = .002).

“That’s clinically meaningful for me as a provider and a clinician and a researcher when you’re getting the PTSD symptom change differences in parallel with the improvement in functional outcome,” she said. “I see that as the clinically meaningful gauge.”

In terms of safety, 3.9% of the participants in the brexpiprazole/sertraline group and 10.2% of those in the sertraline/placebo group discontinued treatment because of adverse events.

In both the combination and control groups, the only treatment-emergent adverse event with an incidence of more than 10% was nausea (12.2% vs 11.7%, respectively).

At the last visit, the mean change in body weight from baseline was an increase of 1.3 kg for brexpiprazole plus sertraline vs 0 kg for sertraline alone. Rates of fatigue (6.8% vs 4.1%) and somnolence (5.4% vs 2.6%) were also higher with brexpiprazole plus sertraline.

 

A Trio of Clinical Trials

The findings are part of a larger program reported by the drug makers that includes a flexible-dose brexpiprazole phase 2 trial that met the same CAPS-5 primary endpoint and a second phase 3 trial (072 study) that did not.

“We’ve looked at that data and the sertraline/placebo response was a lot higher, so it was not due to a lack of response with the combination but due to a more robust response with the active control,” Davis said. “But we want to point out for that 072 study, there was still important separation between the combination and sertraline plus placebo on the functional outcome.”

All three trials ran for 12 weeks, so longer-term efficacy and safety data are needed, she said. Other limitations of the published phase 3 study are the patient eligibility criteria, restrictions on concomitant therapy, and lack of non-US sites, which many limit generalizability, the authors noted.

“Specifically, the exclusion of patients with a current major depressive episode is both a strength (to show a specific effect on PTSD) and a limitation (given the high prevalence of comorbid depression in PTSD),” they added.

 

Kudos, Caveats

Reached for comment, Vincent F. Capaldi, II, MD, ScM, professor and chair, department of psychiatry, Uniformed Services University of the Health Sciences School of Medicine, Bethesda, Maryland, said the exclusion of these patients is a limitation but that the study was well designed and conducted in a large sample across the United States.

“The findings suggest that brexpiprazole plus sertraline is a more effective treatment for PTSD than sertraline alone,” he said. “This finding is significant for our service members, who suffer from PTSD at higher rates than the general population.”

Additionally, the significant improvement in psychosocial functioning at week 12 “is important because PTSD is known to cause significant social and occupational disability, as well as quality-of-life issues,” he said.

Capaldi pointed out, however, that the study was conducted only at US sites and did not specifically target military/veteran persons, which may limit applicability to these unique populations.

“While subgroup analyses were generally consistent with the primary analysis, the study was not powered to detect differences between subgroups,” he added. “These subgroup analyses are quite important when considering military and veteran populations.”

Further research is needed to explore whether certain traumas are more responsive to combination treatment, the efficacy of augmenting existing sertraline therapy, and the specific mechanisms of brexpiprazole driving the improved outcomes, Capaldi said.

This study was funded by Otsuka Pharmaceutical Development & Commercialization, which was involved in the design, conduct, and data analysis. Davis reported receiving advisory board fees from Otsuka and Boehringer Ingelheim; lecture fees from Clinical Care Options; and grants from Alkermes, the Veterans Affairs, Patient-Centered Outcomes Research Institute, Department of Defense, and Social Finance. Several coauthors are employees of Otsuka. Krystal reported serving as a consultant for Otsuka America Pharmaceutical, Aptinyx, Biogen, IDEC, Bionomics, Boehringer Ingelheim International, Clearmind Medicine, Cybin IRL, Enveric Biosciences, Epiodyne, EpiVario, Janssen, Jazz Pharmaceuticals, Perception Neuroscience, Praxis Precision Medicines, Springcare, and Sunovion Pharmaceuticals. Krystal also reported serving as a scientific advisory board member for several companies and holding several patents.

A version of this article appeared on Medscape.com.

A drug that combines the atypical antipsychotic brexpiprazole and the selective serotonin reuptake inhibitor sertraline provides significantly greater relief of posttraumatic stress disorder (PTSD) symptoms than sertraline plus placebo, results of a phase 3 trial showed.

The medication is currently under review by the Food and Drug Administration (FDA) and if approved, will be the first pharmacologic option for PTSD in more than 20 years.

The trial met its primary endpoint of change in the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) (CAPS-5) total score at week 10 and secondary patient-reported outcomes of PTSD symptoms, anxiety, and depression.

“And what is really cool, what’s really impactful is the combination worked better than sertraline plus placebo on a brief inventory of psychosocial functioning,” study investigator Lori L. Davis, a senior research psychiatrist, Birmingham Veterans Affairs Health Care System in Alabama, said in an interview.

“We can treat symptoms but that’s where the rubber meets the road, in terms of are they functioning better,” added Davis, who is also an adjunct professor of psychiatry, Heersink School of Medicine, University of Alabama at Birmingham.

The findings were published online on December 18 in JAMA Psychiatry and reported in May 2024 as part of a trio of trials conducted by Otsuka Pharmaceutical and Lundbeck Pharmaceuticals, codevelopers of the drug.

 

Clinically Meaningful

The FDA accepted the companies’ supplemental new drug application in June with a decision on approval expected in early February 2025.

“This study provides promising results for a medication that may be an important new option for PTSD,” John Krystal, MD, director, Clinical Neuroscience Division, National Center for PTSD, US Department of Veterans Affairs, who was not involved in the research, said in an interview. “New PTSD treatments are a high priority.”

Currently, there are two FDA-approved medication treatments for PTSD — sertraline and paroxetine.

“They are helpful for many people, but patients are often left with residual symptoms or tolerability issues,” noted Krystal, who is also professor and chair of psychiatry, Yale University, New Haven, Connecticut.

“New medications that might address the important ‘effectiveness gap’ in PTSD could help to reduce the remaining distress, disability, and suicide risk associated with PTSD.” 

The double-blind, phase 3 trial included 416 adults aged 18-65 years with a DSM-5 diagnosis of PTSD and symptoms for at least 6 months prior to screening. Patients underwent a 1-week placebo-run in period followed by randomization to daily oral brexpiprazole 2-3 mg plus sertraline 150 mg or daily sertraline 150 mg plus placebo for 11 weeks.

Participants’ mean age was 37.4 years, 74.5% were women, and mean CAPS-5 total score was 38.4, suggesting moderate to high severity PTSD, Davis said. The average time from the index traumatic event was 4 years and three fourths had no prior exposure to PTSD prescription medications.

At week 10, the mean change in CAPS-5 score from randomization was –19.2 points in the brexpiprazole plus sertraline group and –13.6 points in the sertraline plus placebo group (95% CI, –8.79 to –2.38; P < .001).

Asked whether the 5.59-point treatment difference is clinically meaningful, Davis said there is no widely agreed definition for change in CAPS-5 total score but that a within-group reduction of more than 10-13 points is most-often cited as being clinically meaningful.

The key secondary endpoint of least square mean change in the patient-reported Brief Inventory of Psychosocial Function total score from baseline to week 12 was –33.8 with the combination vs –21.8 with sertraline plus placebo (95% CI, –19.4 to –4.62; P = .002).

“That’s clinically meaningful for me as a provider and a clinician and a researcher when you’re getting the PTSD symptom change differences in parallel with the improvement in functional outcome,” she said. “I see that as the clinically meaningful gauge.”

In terms of safety, 3.9% of the participants in the brexpiprazole/sertraline group and 10.2% of those in the sertraline/placebo group discontinued treatment because of adverse events.

In both the combination and control groups, the only treatment-emergent adverse event with an incidence of more than 10% was nausea (12.2% vs 11.7%, respectively).

At the last visit, the mean change in body weight from baseline was an increase of 1.3 kg for brexpiprazole plus sertraline vs 0 kg for sertraline alone. Rates of fatigue (6.8% vs 4.1%) and somnolence (5.4% vs 2.6%) were also higher with brexpiprazole plus sertraline.

 

A Trio of Clinical Trials

The findings are part of a larger program reported by the drug makers that includes a flexible-dose brexpiprazole phase 2 trial that met the same CAPS-5 primary endpoint and a second phase 3 trial (072 study) that did not.

“We’ve looked at that data and the sertraline/placebo response was a lot higher, so it was not due to a lack of response with the combination but due to a more robust response with the active control,” Davis said. “But we want to point out for that 072 study, there was still important separation between the combination and sertraline plus placebo on the functional outcome.”

All three trials ran for 12 weeks, so longer-term efficacy and safety data are needed, she said. Other limitations of the published phase 3 study are the patient eligibility criteria, restrictions on concomitant therapy, and lack of non-US sites, which many limit generalizability, the authors noted.

“Specifically, the exclusion of patients with a current major depressive episode is both a strength (to show a specific effect on PTSD) and a limitation (given the high prevalence of comorbid depression in PTSD),” they added.

 

Kudos, Caveats

Reached for comment, Vincent F. Capaldi, II, MD, ScM, professor and chair, department of psychiatry, Uniformed Services University of the Health Sciences School of Medicine, Bethesda, Maryland, said the exclusion of these patients is a limitation but that the study was well designed and conducted in a large sample across the United States.

“The findings suggest that brexpiprazole plus sertraline is a more effective treatment for PTSD than sertraline alone,” he said. “This finding is significant for our service members, who suffer from PTSD at higher rates than the general population.”

Additionally, the significant improvement in psychosocial functioning at week 12 “is important because PTSD is known to cause significant social and occupational disability, as well as quality-of-life issues,” he said.

Capaldi pointed out, however, that the study was conducted only at US sites and did not specifically target military/veteran persons, which may limit applicability to these unique populations.

“While subgroup analyses were generally consistent with the primary analysis, the study was not powered to detect differences between subgroups,” he added. “These subgroup analyses are quite important when considering military and veteran populations.”

Further research is needed to explore whether certain traumas are more responsive to combination treatment, the efficacy of augmenting existing sertraline therapy, and the specific mechanisms of brexpiprazole driving the improved outcomes, Capaldi said.

This study was funded by Otsuka Pharmaceutical Development & Commercialization, which was involved in the design, conduct, and data analysis. Davis reported receiving advisory board fees from Otsuka and Boehringer Ingelheim; lecture fees from Clinical Care Options; and grants from Alkermes, the Veterans Affairs, Patient-Centered Outcomes Research Institute, Department of Defense, and Social Finance. Several coauthors are employees of Otsuka. Krystal reported serving as a consultant for Otsuka America Pharmaceutical, Aptinyx, Biogen, IDEC, Bionomics, Boehringer Ingelheim International, Clearmind Medicine, Cybin IRL, Enveric Biosciences, Epiodyne, EpiVario, Janssen, Jazz Pharmaceuticals, Perception Neuroscience, Praxis Precision Medicines, Springcare, and Sunovion Pharmaceuticals. Krystal also reported serving as a scientific advisory board member for several companies and holding several patents.

A version of this article appeared on Medscape.com.

Of all the currently available pharmacological and nonpharmacological therapies for attention deficit and hyperactivity disorder (ADHD) in adults, only stimulants and atomoxetine are effective at reducing core symptoms, results of a large comprehensive meta-analysis showed.

The study of 113 randomized controlled trials with nearly 15,000 adults with a formal diagnosis of ADHD also revealed that atomoxetine is less acceptable to patients and that results of efficacy of nonpharmacological strategies are inconsistent.

Data on long-term efficacy of ADHD therapies are lacking, investigators noted, so these results only apply to short-term efficacy.

“There is a lot of controversy about medication, so these are quite reassuring data and certainly reinforce the role of medication as a treatment for ADHD,” study investigator Samuele Cortese, MD, PhD, with University of Southampton, England, said during a press briefing hosted by the UK Science Media Center where the findings were released.

The results also point to the “possible role of nonpharmacological interventions, which are currently not well established in current guidelines. However, there is a need for better evidence to fully understand the exact effect of these nonpharmacological interventions,” Cortese noted.

The study was published online in The Lancet Psychiatry. 

 

Bridging the Knowledge Gap

Once thought to be a childhood disorder only, ADHD is now well-known to persist into adulthood, affecting roughly 2.5% of the general adult population worldwide. The comparative benefits and harms of available interventions for ADHD in adults remain unclear.

To address this knowledge gap, researchers did a comprehensive systematic review and component network meta-analysis comparing a broad range of drug and nondrug treatments for adults with ADHD across several outcomes.

For reducing core ADHD symptoms at 12 weeks, only stimulants and atomoxetine were better than placebo in self-reported and clinician-reported rating scales, the study team found.

For stimulants, the standardized mean differences (SMDs) on the self-reported and clinician-reported scales were 0.39 and 0.61, respectively. The corresponding SMDs for atomoxetine were 0.38 and 0.51.

There was no evidence that ADHD medications were better than placebo in improving additional relevant outcomes such as quality of life.

In terms of nondrug interventions, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation were better than placebo only on clinician-reported measures, with SMDs of −1.35, −0.79, −0.77, and −0.78, respectively.

However, the evidence for nondrug strategies is less conclusive overall, with “discordant results across types of raters and based on a small body of evidence,” the authors wrote in their article.

And evidence for long-term efficacy (beyond 12 weeks) for ADHD interventions is “limited and under-investigated,” they said.

Regarding acceptability, all strategies were similar to placebo except for atomoxetine and guanfacine which had lower acceptability than placebo.

“It’s very important to emphasize that we focused on the average effect, not at an individual level,” first author Edoardo Ostinelli, MD, with University of Oxford, England, said at the briefing. “Therefore, we cannot make any recommendation at an individual level. We need studies with individual participant data so that we can personalize treatment.”

Cortese said the information from this analysis may be particularly important for “psychoeducation” of the patient before actually starting with a treatment plan. Patients often ask about nonpharmacological interventions and this study provides the “best synthesis of available data to inform these discussions,” he said.

 

Experts Weigh In 

Several experts weighed in on the results in a statement from the UK Science Media Center.

Celso Arango, MD, PhD, psychiatrist with Gregorio Marañón General University Hospital, Madrid, Spain, noted that there is a “clear shortage of research on ADHD in adulthood, particularly regarding medium-term (beyond 12 weeks) and long-term treatment outcomes. Consequently, the findings are applicable only to short-term treatment.”

Another strength of the study is that it was developed with input from people with ADHD, Arango added, making it “highly relevant.”

The majority of studies available for the analysis involved pharmacological treatments, which is important to consider when interpreting the findings, noted Katya Rubia, PhD, professor of cognitive neuroscience, King’s College London, England.

“For example, for neurostimulation, only 10 studies were included and on very heterogeneous stimulation methods,” Rubia said. “The evidence on the efficacy of neurostimulation is therefore hardly conclusive and more studies are needed to establish their efficacy.”

Roi Cohen Kadosh, PhD, professor of cognitive neuroscience, University of Surrey, Guildford, England, agreed. While the study is a “valuable contribution to the literature,” it sheds light on “both the scarcity of neurostimulation research and the limited exploration of combined treatment approaches for ADHD,” he said.

“While novel neurostimulation methods linked to neuroplasticity — such as those we have demonstrated to be superior in children with ADHD — were not covered here, they have shown promising and lasting benefits. In contrast, research in adults remains relatively underdeveloped. Moving forward, greater emphasis on innovative, tolerable, personalized, and sustainable neurostimulation approaches is essential to meet the unmet clinical needs of adults with ADHD,” Kadosh added.

In a commentary in The Lancet Psychiatry, David Coghill, MD, with The University of Melbourne, Australia, cautioned that the findings do not mean that potential benefits of nonpharmacological interventions should be dismissed.

“While some of the nonpharmacological treatments (eg, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation) showed effects on clinician-rated outcomes similar to, and in some cases greater than, the pharmacological treatments, they did not show the same effects on self-reported outcomes. These interventions were therefore considered less robust than the pharmacological treatments that showed changes on both measurement types,” he wrote.

This study had no commercial funding. Ostinelli had received research and consultancy fees from Angelini Pharma. Cortese received reimbursement for travel and accommodation expenses in relation to lectures delivered for the Association for Child and Adolescent Central Health, the Canadian ADHD Alliance Resource, and the British Association of Psychopharmacology; and had received honoraria from MEDICE; and is chair of the European ADHD Guidelines Group. Arango, Rubia, and Kadosh had no relevant disclosures. Coghill had received honoraria from CCM Conecta, Takeda, Novartis, Servier, and MEDICE.

A version of this article first appeared on Medscape.com.

Of all the currently available pharmacological and nonpharmacological therapies for attention deficit and hyperactivity disorder (ADHD) in adults, only stimulants and atomoxetine are effective at reducing core symptoms, results of a large comprehensive meta-analysis showed.

The study of 113 randomized controlled trials with nearly 15,000 adults with a formal diagnosis of ADHD also revealed that atomoxetine is less acceptable to patients and that results of efficacy of nonpharmacological strategies are inconsistent.

Data on long-term efficacy of ADHD therapies are lacking, investigators noted, so these results only apply to short-term efficacy.

“There is a lot of controversy about medication, so these are quite reassuring data and certainly reinforce the role of medication as a treatment for ADHD,” study investigator Samuele Cortese, MD, PhD, with University of Southampton, England, said during a press briefing hosted by the UK Science Media Center where the findings were released.

The results also point to the “possible role of nonpharmacological interventions, which are currently not well established in current guidelines. However, there is a need for better evidence to fully understand the exact effect of these nonpharmacological interventions,” Cortese noted.

The study was published online in The Lancet Psychiatry. 

 

Bridging the Knowledge Gap

Once thought to be a childhood disorder only, ADHD is now well-known to persist into adulthood, affecting roughly 2.5% of the general adult population worldwide. The comparative benefits and harms of available interventions for ADHD in adults remain unclear.

To address this knowledge gap, researchers did a comprehensive systematic review and component network meta-analysis comparing a broad range of drug and nondrug treatments for adults with ADHD across several outcomes.

For reducing core ADHD symptoms at 12 weeks, only stimulants and atomoxetine were better than placebo in self-reported and clinician-reported rating scales, the study team found.

For stimulants, the standardized mean differences (SMDs) on the self-reported and clinician-reported scales were 0.39 and 0.61, respectively. The corresponding SMDs for atomoxetine were 0.38 and 0.51.

There was no evidence that ADHD medications were better than placebo in improving additional relevant outcomes such as quality of life.

In terms of nondrug interventions, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation were better than placebo only on clinician-reported measures, with SMDs of −1.35, −0.79, −0.77, and −0.78, respectively.

However, the evidence for nondrug strategies is less conclusive overall, with “discordant results across types of raters and based on a small body of evidence,” the authors wrote in their article.

And evidence for long-term efficacy (beyond 12 weeks) for ADHD interventions is “limited and under-investigated,” they said.

Regarding acceptability, all strategies were similar to placebo except for atomoxetine and guanfacine which had lower acceptability than placebo.

“It’s very important to emphasize that we focused on the average effect, not at an individual level,” first author Edoardo Ostinelli, MD, with University of Oxford, England, said at the briefing. “Therefore, we cannot make any recommendation at an individual level. We need studies with individual participant data so that we can personalize treatment.”

Cortese said the information from this analysis may be particularly important for “psychoeducation” of the patient before actually starting with a treatment plan. Patients often ask about nonpharmacological interventions and this study provides the “best synthesis of available data to inform these discussions,” he said.

 

Experts Weigh In 

Several experts weighed in on the results in a statement from the UK Science Media Center.

Celso Arango, MD, PhD, psychiatrist with Gregorio Marañón General University Hospital, Madrid, Spain, noted that there is a “clear shortage of research on ADHD in adulthood, particularly regarding medium-term (beyond 12 weeks) and long-term treatment outcomes. Consequently, the findings are applicable only to short-term treatment.”

Another strength of the study is that it was developed with input from people with ADHD, Arango added, making it “highly relevant.”

The majority of studies available for the analysis involved pharmacological treatments, which is important to consider when interpreting the findings, noted Katya Rubia, PhD, professor of cognitive neuroscience, King’s College London, England.

“For example, for neurostimulation, only 10 studies were included and on very heterogeneous stimulation methods,” Rubia said. “The evidence on the efficacy of neurostimulation is therefore hardly conclusive and more studies are needed to establish their efficacy.”

Roi Cohen Kadosh, PhD, professor of cognitive neuroscience, University of Surrey, Guildford, England, agreed. While the study is a “valuable contribution to the literature,” it sheds light on “both the scarcity of neurostimulation research and the limited exploration of combined treatment approaches for ADHD,” he said.

“While novel neurostimulation methods linked to neuroplasticity — such as those we have demonstrated to be superior in children with ADHD — were not covered here, they have shown promising and lasting benefits. In contrast, research in adults remains relatively underdeveloped. Moving forward, greater emphasis on innovative, tolerable, personalized, and sustainable neurostimulation approaches is essential to meet the unmet clinical needs of adults with ADHD,” Kadosh added.

In a commentary in The Lancet Psychiatry, David Coghill, MD, with The University of Melbourne, Australia, cautioned that the findings do not mean that potential benefits of nonpharmacological interventions should be dismissed.

“While some of the nonpharmacological treatments (eg, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation) showed effects on clinician-rated outcomes similar to, and in some cases greater than, the pharmacological treatments, they did not show the same effects on self-reported outcomes. These interventions were therefore considered less robust than the pharmacological treatments that showed changes on both measurement types,” he wrote.

This study had no commercial funding. Ostinelli had received research and consultancy fees from Angelini Pharma. Cortese received reimbursement for travel and accommodation expenses in relation to lectures delivered for the Association for Child and Adolescent Central Health, the Canadian ADHD Alliance Resource, and the British Association of Psychopharmacology; and had received honoraria from MEDICE; and is chair of the European ADHD Guidelines Group. Arango, Rubia, and Kadosh had no relevant disclosures. Coghill had received honoraria from CCM Conecta, Takeda, Novartis, Servier, and MEDICE.

A version of this article first appeared on Medscape.com.

Of all the currently available pharmacological and nonpharmacological therapies for attention deficit and hyperactivity disorder (ADHD) in adults, only stimulants and atomoxetine are effective at reducing core symptoms, results of a large comprehensive meta-analysis showed.

The study of 113 randomized controlled trials with nearly 15,000 adults with a formal diagnosis of ADHD also revealed that atomoxetine is less acceptable to patients and that results of efficacy of nonpharmacological strategies are inconsistent.

Data on long-term efficacy of ADHD therapies are lacking, investigators noted, so these results only apply to short-term efficacy.

“There is a lot of controversy about medication, so these are quite reassuring data and certainly reinforce the role of medication as a treatment for ADHD,” study investigator Samuele Cortese, MD, PhD, with University of Southampton, England, said during a press briefing hosted by the UK Science Media Center where the findings were released.

The results also point to the “possible role of nonpharmacological interventions, which are currently not well established in current guidelines. However, there is a need for better evidence to fully understand the exact effect of these nonpharmacological interventions,” Cortese noted.

The study was published online in The Lancet Psychiatry. 

 

Bridging the Knowledge Gap

Once thought to be a childhood disorder only, ADHD is now well-known to persist into adulthood, affecting roughly 2.5% of the general adult population worldwide. The comparative benefits and harms of available interventions for ADHD in adults remain unclear.

To address this knowledge gap, researchers did a comprehensive systematic review and component network meta-analysis comparing a broad range of drug and nondrug treatments for adults with ADHD across several outcomes.

For reducing core ADHD symptoms at 12 weeks, only stimulants and atomoxetine were better than placebo in self-reported and clinician-reported rating scales, the study team found.

For stimulants, the standardized mean differences (SMDs) on the self-reported and clinician-reported scales were 0.39 and 0.61, respectively. The corresponding SMDs for atomoxetine were 0.38 and 0.51.

There was no evidence that ADHD medications were better than placebo in improving additional relevant outcomes such as quality of life.

In terms of nondrug interventions, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation were better than placebo only on clinician-reported measures, with SMDs of −1.35, −0.79, −0.77, and −0.78, respectively.

However, the evidence for nondrug strategies is less conclusive overall, with “discordant results across types of raters and based on a small body of evidence,” the authors wrote in their article.

And evidence for long-term efficacy (beyond 12 weeks) for ADHD interventions is “limited and under-investigated,” they said.

Regarding acceptability, all strategies were similar to placebo except for atomoxetine and guanfacine which had lower acceptability than placebo.

“It’s very important to emphasize that we focused on the average effect, not at an individual level,” first author Edoardo Ostinelli, MD, with University of Oxford, England, said at the briefing. “Therefore, we cannot make any recommendation at an individual level. We need studies with individual participant data so that we can personalize treatment.”

Cortese said the information from this analysis may be particularly important for “psychoeducation” of the patient before actually starting with a treatment plan. Patients often ask about nonpharmacological interventions and this study provides the “best synthesis of available data to inform these discussions,” he said.

 

Experts Weigh In 

Several experts weighed in on the results in a statement from the UK Science Media Center.

Celso Arango, MD, PhD, psychiatrist with Gregorio Marañón General University Hospital, Madrid, Spain, noted that there is a “clear shortage of research on ADHD in adulthood, particularly regarding medium-term (beyond 12 weeks) and long-term treatment outcomes. Consequently, the findings are applicable only to short-term treatment.”

Another strength of the study is that it was developed with input from people with ADHD, Arango added, making it “highly relevant.”

The majority of studies available for the analysis involved pharmacological treatments, which is important to consider when interpreting the findings, noted Katya Rubia, PhD, professor of cognitive neuroscience, King’s College London, England.

“For example, for neurostimulation, only 10 studies were included and on very heterogeneous stimulation methods,” Rubia said. “The evidence on the efficacy of neurostimulation is therefore hardly conclusive and more studies are needed to establish their efficacy.”

Roi Cohen Kadosh, PhD, professor of cognitive neuroscience, University of Surrey, Guildford, England, agreed. While the study is a “valuable contribution to the literature,” it sheds light on “both the scarcity of neurostimulation research and the limited exploration of combined treatment approaches for ADHD,” he said.

“While novel neurostimulation methods linked to neuroplasticity — such as those we have demonstrated to be superior in children with ADHD — were not covered here, they have shown promising and lasting benefits. In contrast, research in adults remains relatively underdeveloped. Moving forward, greater emphasis on innovative, tolerable, personalized, and sustainable neurostimulation approaches is essential to meet the unmet clinical needs of adults with ADHD,” Kadosh added.

In a commentary in The Lancet Psychiatry, David Coghill, MD, with The University of Melbourne, Australia, cautioned that the findings do not mean that potential benefits of nonpharmacological interventions should be dismissed.

“While some of the nonpharmacological treatments (eg, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation) showed effects on clinician-rated outcomes similar to, and in some cases greater than, the pharmacological treatments, they did not show the same effects on self-reported outcomes. These interventions were therefore considered less robust than the pharmacological treatments that showed changes on both measurement types,” he wrote.

This study had no commercial funding. Ostinelli had received research and consultancy fees from Angelini Pharma. Cortese received reimbursement for travel and accommodation expenses in relation to lectures delivered for the Association for Child and Adolescent Central Health, the Canadian ADHD Alliance Resource, and the British Association of Psychopharmacology; and had received honoraria from MEDICE; and is chair of the European ADHD Guidelines Group. Arango, Rubia, and Kadosh had no relevant disclosures. Coghill had received honoraria from CCM Conecta, Takeda, Novartis, Servier, and MEDICE.

A version of this article first appeared on Medscape.com.

In the latest effort to address the mental health crisis among adolescents, legislation in California would require social media platforms to come with a “black box” mental health warning label.

Despite growing evidence linking young people’s use of social media to significant health risks including depression, anxiety, and suicidal thoughts, social media companies have failed to be transparent about the risks, said Assembly member Rebecca Bauer-Kahan (D-Orinda), who introduced Assembly Bill (AB) 56.

“AB 56 ensures that families are armed with clear, actionable information to understand these dangers and make decisions that prioritizes their children’s well-being,” she said in a press release.

Bauer-Kahan noted that 95% of teens report using at least one social media platform and that more than one third say they use social media almost constantly.

“There is a powerful profit motive to keep our young people hooked online and engaged and it is exploiting the human psychology with notifications, likes, endless scrolling, and algorithmic amplification that is harming our children every day,” she said at a press conference on December 9 announcing the bill.

The warning labels are an equitable and transparent way to communicate the risks that social media poses to young users, California’s Attorney General Rob Bonta, a sponsor of AB 56, said in a press release.

Speaking at the press conference, Bonta said social media has many “incredible benefits” from giving people an outlet of expression to providing access to critical information but “there is no disputing the fact, it can have an enormously detrimental and dangerous impact on our young people. You cannot debate that. Our children are suffering.”

If AB 56 is successful, he said social media platforms would be required to display a “black box warning” for all users that would appear upon the first use of a platform and weekly thereafter.

The proposed language for the warning label is: “The Surgeon General has advised that there are ample indicators that social media can have a profound risk of harm to the mental health and well-being of children and adolescents.”

“This warning label isn’t a panacea, we know that, but it is another tool in our toolbox. It’s one prong in what has to be a multi-pronged continued, coordinated effort to address this public health crisis,” Bonta said.

Reached for comment, Bonta’s office said sponsorship of the bill was informed by their ongoing work to create a safer online space for children and teens and by the US Surgeon General’s call to Congress to add warning labels to social media.

In June, US Surgeon General Vivek Murthy, MD, said a Surgeon General’s warning label is needed to address the mental health emergency among adolescents and noted that evidence from tobacco studies shows warning labels can increase awareness and change behavior. In September, the attorneys general of 42 states announced their support of the proposal.

Also in September, US Senators John Fetterman (D-PA) and Katie Britt (R-AL) introduced the Stop the Scroll Act to create a mental health warning label requirement for social media platforms.

In a controversial move in November, Australia passed the world’s first law banning social media for children younger than 16 years. The law gives platforms such as TikTok, Facebook, X, Snapchat, and Instagram 1 year to figure out how to implement the ban before facing fines of up 50 million Australian dollars ($33 million) for systemic failures to prevent children younger than 16 years from holding accounts.

 

‘A Broken Fire Alarm’

“Slapping a warning label on social media is like a broken fire alarm going off with no evidence of smoke. It ignores the reality that most teens view social media as an important outlet for social connection,” Todd O’Boyle, with the tech industry policy group Chamber of Progress, said in a statement on AB 56.

He highlighted a 2022 Pew Research Center survey reporting that most teens credit social media with deepening connections and providing a support network and a 2020 study reporting that social media is not a strong or consistent risk factor for depressive symptoms in US adolescents.

O’Boyle predicted that, without strong evidence, AB 56 will run into the same “First Amendment buzzsaw” that has doomed other California kids’ bills.

Pediatrician Jason Nagata, MD, University of California San Francisco, points out in Bonta’s press release that social media can displace time for other healthful activities including sleep, exercise, and in-person socialization.

“While social media can provide educational content, it can also provide misinformation about health and expose children to content that damages their mental well-being. These are risks that adolescents and their parents should be aware of,” Nagata said.

Indeed, a tearful Victoria Hinks of Larkspur, California, spoke at the press conference of her 16-year-old daughter, Alexandra, who committed suicide 4 months ago after being sucked into social media and served content on self-harm, eating disorders, suicidal ideation, and glamorization of suicide.

“She was led down dark rabbit holes she had no hope of escaping,” Hinks said. “There is not a bone in my body that doubts social media played a role leading her to that final irreversible decision.”

Jim Steyer, CEO and founder of Common Sense Media, applauded California for being the first state to introduce social media warning label legislation. The group plans to lobby for similar proposals in other states he said at the press conference, noting that there are “tens of thousands of Alexandras out there.”

“We have seat belt laws, we have warning labels on cigarettes and alcohol, and that’s what we’re doing here,” Steyer said. “It’s a straightforward simple proposition, which is put your kids and teenagers first, put their self-interest first and hold the largest, most powerful, and wealthy companies in all of our lifetimes accountable for the harms that have happened on their platforms.”

A version of this article first appeared on Medscape.com.

In the latest effort to address the mental health crisis among adolescents, legislation in California would require social media platforms to come with a “black box” mental health warning label.

Despite growing evidence linking young people’s use of social media to significant health risks including depression, anxiety, and suicidal thoughts, social media companies have failed to be transparent about the risks, said Assembly member Rebecca Bauer-Kahan (D-Orinda), who introduced Assembly Bill (AB) 56.

“AB 56 ensures that families are armed with clear, actionable information to understand these dangers and make decisions that prioritizes their children’s well-being,” she said in a press release.

Bauer-Kahan noted that 95% of teens report using at least one social media platform and that more than one third say they use social media almost constantly.

“There is a powerful profit motive to keep our young people hooked online and engaged and it is exploiting the human psychology with notifications, likes, endless scrolling, and algorithmic amplification that is harming our children every day,” she said at a press conference on December 9 announcing the bill.

The warning labels are an equitable and transparent way to communicate the risks that social media poses to young users, California’s Attorney General Rob Bonta, a sponsor of AB 56, said in a press release.

Speaking at the press conference, Bonta said social media has many “incredible benefits” from giving people an outlet of expression to providing access to critical information but “there is no disputing the fact, it can have an enormously detrimental and dangerous impact on our young people. You cannot debate that. Our children are suffering.”

If AB 56 is successful, he said social media platforms would be required to display a “black box warning” for all users that would appear upon the first use of a platform and weekly thereafter.

The proposed language for the warning label is: “The Surgeon General has advised that there are ample indicators that social media can have a profound risk of harm to the mental health and well-being of children and adolescents.”

“This warning label isn’t a panacea, we know that, but it is another tool in our toolbox. It’s one prong in what has to be a multi-pronged continued, coordinated effort to address this public health crisis,” Bonta said.

Reached for comment, Bonta’s office said sponsorship of the bill was informed by their ongoing work to create a safer online space for children and teens and by the US Surgeon General’s call to Congress to add warning labels to social media.

In June, US Surgeon General Vivek Murthy, MD, said a Surgeon General’s warning label is needed to address the mental health emergency among adolescents and noted that evidence from tobacco studies shows warning labels can increase awareness and change behavior. In September, the attorneys general of 42 states announced their support of the proposal.

Also in September, US Senators John Fetterman (D-PA) and Katie Britt (R-AL) introduced the Stop the Scroll Act to create a mental health warning label requirement for social media platforms.

In a controversial move in November, Australia passed the world’s first law banning social media for children younger than 16 years. The law gives platforms such as TikTok, Facebook, X, Snapchat, and Instagram 1 year to figure out how to implement the ban before facing fines of up 50 million Australian dollars ($33 million) for systemic failures to prevent children younger than 16 years from holding accounts.

 

‘A Broken Fire Alarm’

“Slapping a warning label on social media is like a broken fire alarm going off with no evidence of smoke. It ignores the reality that most teens view social media as an important outlet for social connection,” Todd O’Boyle, with the tech industry policy group Chamber of Progress, said in a statement on AB 56.

He highlighted a 2022 Pew Research Center survey reporting that most teens credit social media with deepening connections and providing a support network and a 2020 study reporting that social media is not a strong or consistent risk factor for depressive symptoms in US adolescents.

O’Boyle predicted that, without strong evidence, AB 56 will run into the same “First Amendment buzzsaw” that has doomed other California kids’ bills.

Pediatrician Jason Nagata, MD, University of California San Francisco, points out in Bonta’s press release that social media can displace time for other healthful activities including sleep, exercise, and in-person socialization.

“While social media can provide educational content, it can also provide misinformation about health and expose children to content that damages their mental well-being. These are risks that adolescents and their parents should be aware of,” Nagata said.

Indeed, a tearful Victoria Hinks of Larkspur, California, spoke at the press conference of her 16-year-old daughter, Alexandra, who committed suicide 4 months ago after being sucked into social media and served content on self-harm, eating disorders, suicidal ideation, and glamorization of suicide.

“She was led down dark rabbit holes she had no hope of escaping,” Hinks said. “There is not a bone in my body that doubts social media played a role leading her to that final irreversible decision.”

Jim Steyer, CEO and founder of Common Sense Media, applauded California for being the first state to introduce social media warning label legislation. The group plans to lobby for similar proposals in other states he said at the press conference, noting that there are “tens of thousands of Alexandras out there.”

“We have seat belt laws, we have warning labels on cigarettes and alcohol, and that’s what we’re doing here,” Steyer said. “It’s a straightforward simple proposition, which is put your kids and teenagers first, put their self-interest first and hold the largest, most powerful, and wealthy companies in all of our lifetimes accountable for the harms that have happened on their platforms.”

A version of this article first appeared on Medscape.com.

In the latest effort to address the mental health crisis among adolescents, legislation in California would require social media platforms to come with a “black box” mental health warning label.

Despite growing evidence linking young people’s use of social media to significant health risks including depression, anxiety, and suicidal thoughts, social media companies have failed to be transparent about the risks, said Assembly member Rebecca Bauer-Kahan (D-Orinda), who introduced Assembly Bill (AB) 56.

“AB 56 ensures that families are armed with clear, actionable information to understand these dangers and make decisions that prioritizes their children’s well-being,” she said in a press release.

Bauer-Kahan noted that 95% of teens report using at least one social media platform and that more than one third say they use social media almost constantly.

“There is a powerful profit motive to keep our young people hooked online and engaged and it is exploiting the human psychology with notifications, likes, endless scrolling, and algorithmic amplification that is harming our children every day,” she said at a press conference on December 9 announcing the bill.

The warning labels are an equitable and transparent way to communicate the risks that social media poses to young users, California’s Attorney General Rob Bonta, a sponsor of AB 56, said in a press release.

Speaking at the press conference, Bonta said social media has many “incredible benefits” from giving people an outlet of expression to providing access to critical information but “there is no disputing the fact, it can have an enormously detrimental and dangerous impact on our young people. You cannot debate that. Our children are suffering.”

If AB 56 is successful, he said social media platforms would be required to display a “black box warning” for all users that would appear upon the first use of a platform and weekly thereafter.

The proposed language for the warning label is: “The Surgeon General has advised that there are ample indicators that social media can have a profound risk of harm to the mental health and well-being of children and adolescents.”

“This warning label isn’t a panacea, we know that, but it is another tool in our toolbox. It’s one prong in what has to be a multi-pronged continued, coordinated effort to address this public health crisis,” Bonta said.

Reached for comment, Bonta’s office said sponsorship of the bill was informed by their ongoing work to create a safer online space for children and teens and by the US Surgeon General’s call to Congress to add warning labels to social media.

In June, US Surgeon General Vivek Murthy, MD, said a Surgeon General’s warning label is needed to address the mental health emergency among adolescents and noted that evidence from tobacco studies shows warning labels can increase awareness and change behavior. In September, the attorneys general of 42 states announced their support of the proposal.

Also in September, US Senators John Fetterman (D-PA) and Katie Britt (R-AL) introduced the Stop the Scroll Act to create a mental health warning label requirement for social media platforms.

In a controversial move in November, Australia passed the world’s first law banning social media for children younger than 16 years. The law gives platforms such as TikTok, Facebook, X, Snapchat, and Instagram 1 year to figure out how to implement the ban before facing fines of up 50 million Australian dollars ($33 million) for systemic failures to prevent children younger than 16 years from holding accounts.

 

‘A Broken Fire Alarm’

“Slapping a warning label on social media is like a broken fire alarm going off with no evidence of smoke. It ignores the reality that most teens view social media as an important outlet for social connection,” Todd O’Boyle, with the tech industry policy group Chamber of Progress, said in a statement on AB 56.

He highlighted a 2022 Pew Research Center survey reporting that most teens credit social media with deepening connections and providing a support network and a 2020 study reporting that social media is not a strong or consistent risk factor for depressive symptoms in US adolescents.

O’Boyle predicted that, without strong evidence, AB 56 will run into the same “First Amendment buzzsaw” that has doomed other California kids’ bills.

Pediatrician Jason Nagata, MD, University of California San Francisco, points out in Bonta’s press release that social media can displace time for other healthful activities including sleep, exercise, and in-person socialization.

“While social media can provide educational content, it can also provide misinformation about health and expose children to content that damages their mental well-being. These are risks that adolescents and their parents should be aware of,” Nagata said.

Indeed, a tearful Victoria Hinks of Larkspur, California, spoke at the press conference of her 16-year-old daughter, Alexandra, who committed suicide 4 months ago after being sucked into social media and served content on self-harm, eating disorders, suicidal ideation, and glamorization of suicide.

“She was led down dark rabbit holes she had no hope of escaping,” Hinks said. “There is not a bone in my body that doubts social media played a role leading her to that final irreversible decision.”

Jim Steyer, CEO and founder of Common Sense Media, applauded California for being the first state to introduce social media warning label legislation. The group plans to lobby for similar proposals in other states he said at the press conference, noting that there are “tens of thousands of Alexandras out there.”

“We have seat belt laws, we have warning labels on cigarettes and alcohol, and that’s what we’re doing here,” Steyer said. “It’s a straightforward simple proposition, which is put your kids and teenagers first, put their self-interest first and hold the largest, most powerful, and wealthy companies in all of our lifetimes accountable for the harms that have happened on their platforms.”

A version of this article first appeared on Medscape.com.

TOPLINE:

InterRhythmic care (IRC), a novel digital intervention, was linked to greater improvements in depressive symptoms, anxiety, interpersonal relationships, and social functioning in patients with major depressive disorder (MDD), compared with internet general psychoeducation in new research.

METHODOLOGY:

• The randomized, single-blind trial included 120 outpatients from the Shanghai Mental Health Center between March and November 2021 with MDD (mean age, 28.2 years; 99% Han Chinese; 83% women) who were randomly assigned to receive either IRC or internet general psychoeducation (control group).
• IRC included computer-based psychoeducation on stabilizing social rhythm regularity and resolution of interpersonal problems plus brief online interactions with clinicians. Patients received 10 minutes of IRC daily, Monday through Friday, for 8 weeks.
• The researchers assessed participants’ depressive symptoms, anxiety symptoms, interpersonal relationships, social function, and biological rhythms using the 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Interpersonal Comprehensive Diagnostic Scale, Sheehan Disability Scale, and Morning and Evening Questionnaire at baseline and at 8 weeks.

TAKEAWAY:

• The participants who received IRC had significantly lower Hamilton Depression Rating total scores than those who received internet general psychoeducation (P < .001).
• The IRC group demonstrated improved anxiety symptoms, as evidenced by lower Hamilton Anxiety Scale total scores, than those observed for the control group (P < .001).
• The IRC group also showed improved outcomes in interpersonal relationships, as indicated by lower Interpersonal Comprehensive Diagnostic Scale total scores (P < .001).
• Social functioning improved significantly in the IRC group, as measured by the Sheehan Disability Scale subscores for work/school (P = .03), social life (P < .001), and family life (P = .001).

IN PRACTICE:

“This study demonstrated that IRC can improve clinical symptoms such as depressive symptoms, anxiety symptoms, interpersonal problems, and social function in patients with MDD. Our study suggested that the IRC can be used in clinical practice,” the investigators wrote.

SOURCE:

The study was led by Chuchen Xu, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine in China. It was published online on November 20, 2024, in The Journal of Psychiatric Research.

LIMITATIONS:

The 8-week follow-up period was considered too short to comprehensively evaluate the intervention’s long-term impact. Additionally, the researchers had to check and supervise assignment completion, which increased research costs and may, therefore, potentially limit broader implementation.

DISCLOSURES:

The investigators reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

InterRhythmic care (IRC), a novel digital intervention, was linked to greater improvements in depressive symptoms, anxiety, interpersonal relationships, and social functioning in patients with major depressive disorder (MDD), compared with internet general psychoeducation in new research.

METHODOLOGY:

• The randomized, single-blind trial included 120 outpatients from the Shanghai Mental Health Center between March and November 2021 with MDD (mean age, 28.2 years; 99% Han Chinese; 83% women) who were randomly assigned to receive either IRC or internet general psychoeducation (control group).
• IRC included computer-based psychoeducation on stabilizing social rhythm regularity and resolution of interpersonal problems plus brief online interactions with clinicians. Patients received 10 minutes of IRC daily, Monday through Friday, for 8 weeks.
• The researchers assessed participants’ depressive symptoms, anxiety symptoms, interpersonal relationships, social function, and biological rhythms using the 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Interpersonal Comprehensive Diagnostic Scale, Sheehan Disability Scale, and Morning and Evening Questionnaire at baseline and at 8 weeks.

TAKEAWAY:

• The participants who received IRC had significantly lower Hamilton Depression Rating total scores than those who received internet general psychoeducation (P < .001).
• The IRC group demonstrated improved anxiety symptoms, as evidenced by lower Hamilton Anxiety Scale total scores, than those observed for the control group (P < .001).
• The IRC group also showed improved outcomes in interpersonal relationships, as indicated by lower Interpersonal Comprehensive Diagnostic Scale total scores (P < .001).
• Social functioning improved significantly in the IRC group, as measured by the Sheehan Disability Scale subscores for work/school (P = .03), social life (P < .001), and family life (P = .001).

IN PRACTICE:

“This study demonstrated that IRC can improve clinical symptoms such as depressive symptoms, anxiety symptoms, interpersonal problems, and social function in patients with MDD. Our study suggested that the IRC can be used in clinical practice,” the investigators wrote.

SOURCE:

The study was led by Chuchen Xu, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine in China. It was published online on November 20, 2024, in The Journal of Psychiatric Research.

LIMITATIONS:

The 8-week follow-up period was considered too short to comprehensively evaluate the intervention’s long-term impact. Additionally, the researchers had to check and supervise assignment completion, which increased research costs and may, therefore, potentially limit broader implementation.

DISCLOSURES:

The investigators reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

InterRhythmic care (IRC), a novel digital intervention, was linked to greater improvements in depressive symptoms, anxiety, interpersonal relationships, and social functioning in patients with major depressive disorder (MDD), compared with internet general psychoeducation in new research.

METHODOLOGY:

• The randomized, single-blind trial included 120 outpatients from the Shanghai Mental Health Center between March and November 2021 with MDD (mean age, 28.2 years; 99% Han Chinese; 83% women) who were randomly assigned to receive either IRC or internet general psychoeducation (control group).
• IRC included computer-based psychoeducation on stabilizing social rhythm regularity and resolution of interpersonal problems plus brief online interactions with clinicians. Patients received 10 minutes of IRC daily, Monday through Friday, for 8 weeks.
• The researchers assessed participants’ depressive symptoms, anxiety symptoms, interpersonal relationships, social function, and biological rhythms using the 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Interpersonal Comprehensive Diagnostic Scale, Sheehan Disability Scale, and Morning and Evening Questionnaire at baseline and at 8 weeks.

TAKEAWAY:

• The participants who received IRC had significantly lower Hamilton Depression Rating total scores than those who received internet general psychoeducation (P < .001).
• The IRC group demonstrated improved anxiety symptoms, as evidenced by lower Hamilton Anxiety Scale total scores, than those observed for the control group (P < .001).
• The IRC group also showed improved outcomes in interpersonal relationships, as indicated by lower Interpersonal Comprehensive Diagnostic Scale total scores (P < .001).
• Social functioning improved significantly in the IRC group, as measured by the Sheehan Disability Scale subscores for work/school (P = .03), social life (P < .001), and family life (P = .001).

IN PRACTICE:

“This study demonstrated that IRC can improve clinical symptoms such as depressive symptoms, anxiety symptoms, interpersonal problems, and social function in patients with MDD. Our study suggested that the IRC can be used in clinical practice,” the investigators wrote.

SOURCE:

The study was led by Chuchen Xu, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine in China. It was published online on November 20, 2024, in The Journal of Psychiatric Research.

LIMITATIONS:

The 8-week follow-up period was considered too short to comprehensively evaluate the intervention’s long-term impact. Additionally, the researchers had to check and supervise assignment completion, which increased research costs and may, therefore, potentially limit broader implementation.

DISCLOSURES:

The investigators reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.