Morning Rounds: August 24-31

This week's roundup covers new data on cardiometabolic risk in patients with serious mental illness and ADHD, alongside a pipeline update on a new indication for an already-approved drug. Policy developments include a milestone in the anticipated US adult ADHD guidelines from APSARD and a landmark settlement over social media's impact on teen mental health.

Policy & Legislation

APSARD Adult ADHD Guidelines Enter Final Review Stage Ahead of Publication

The American Professional Society of ADHD and Related Disorders (APSARD) announced that its US Adult ADHD Guidelines have entered Stage 3, the final review phase before publication.¹ The guidelines are the first of their kind in the US and aim to provide evidence-informed recommendations for the screening, diagnosis, and treatment of ADHD in adults. Stage 3 draws on feedback from a broad range of disciplines involved in ADHD care, as well as individuals with lived experience, following 2 years of work by 3 subcommittees covering screening and diagnosis, medication and medical treatments, and psychosocial and nonmedical interventions. APSARD President Brooke Molina, PhD, called this milestone the final step before publication, with feedback to be incorporated into the manuscript before submission. Clinicians should expect the first formal US framework for adult ADHD care within the next several months, with implications for standardizing diagnostic workup and treatment selection.

Meta Reaches $18 Billion Settlement Over Teen Mental Health Harms

Meta agreed to pay approximately $18 billion to settle a multistate lawsuit brought by 52 attorneys general alleging the company designed Instagram and Facebook to be addictive and harmful to the mental health of minors.³ The settlement, approved by a federal judge, requires Meta to implement a default 2-hour daily screen-time limit for teen accounts, block minors from app access between midnight and 6 am, mute notifications during school hours, and offer a nonalgorithmic feed option. Roughly 70% of the funds will go to states to support youth online safety initiatives, and about 30% of the payment is contingent on whether TikTok and YouTube adopt similar changes. Meta did not admit wrongdoing. For clinicians treating adolescents, the resulting changes to access and screen time may be relevant to conversations about sleep, mood, and social media use.

Clinical Research

GLP-1 Receptor Agonists Linked to Lower Mortality and Cardiovascular Risk in Serious Mental Illness

A target trial emulation published in JAMA Psychiatry found that initiating a glucagon-like peptide-1 receptor agonist (GLP-1 RA) was associated with lower all-cause mortality and fewer major adverse cardiovascular events than initiating a sodium-glucose cotransporter-2 (SGLT2) inhibitor, with greater absolute benefit among adults with serious mental illness.² The study used a multinational database of more than 1.5 million propensity score-matched adults, including those with major depressive disorder, bipolar disorder, and schizophrenia. Among patients with serious mental illness, 4-year mortality was 4.91% with GLP-1 RAs versus 6.45% with SGLT2 inhibitors, with benefits emerging within the first year and driven primarily by semaglutide and tirzepatide. Effects were consistent across subgroups, though the authors note that prospective randomized trials are still needed. For prescribers managing patients with serious mental illness and comorbid cardiometabolic risk, the findings offer preliminary support for favoring GLP-1 RAs when both drug classes are clinically appropriate.

ADHD Linked to Worse Cardiorenal Outcomes After Starting Antihypertensive Medications

A nationwide cohort study found that adults with ADHD who initiated antihypertensive medications had significantly higher long-term rates of heart failure hospitalization, stroke, and cardiorenal death compared with adults without ADHD starting the same medications.⁴ The study used multistate modeling to track cardiorenal illness trajectories following antihypertensive initiation, identifying ADHD as an independent risk factor for adverse outcomes over follow-up. The authors did not attribute the disparity to a single mechanism, though the findings raise questions about differences in adherence, comorbidity burden, or monitoring in this population. The study adds to a growing body of literature examining cardiovascular risk in adults with ADHD independent of stimulant treatment, and reinforces that ADHD itself, not just its pharmacologic management, may carry downstream cardiometabolic consequences. Prescribers managing patients with both ADHD and hypertension may want to consider closer cardiorenal monitoring when starting antihypertensive therapy, particularly given the elevated stroke and heart failure signal seen here.

Pharmaceutical Updates

First Patient Dosed in Phase 3 SUMMIT Trial of AXS-05 for Smoking Cessation

Axsome Therapeutics announced that the first patient has been dosed in the SUMMIT phase 3 trial evaluating AXS-05 (dextromethorphan-bupropion) as a smoking cessation treatment in adults.⁵ AXS-05, marketed as Auvelity for major depressive disorder and Alzheimer disease agitation, is an oral NMDA receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor not yet approved for smoking cessation. In the randomized, double-blind, active- and placebo-controlled trial, active smokers will be assigned 1:1:1 to AXS-05, bupropion, or placebo for approximately 12 weeks, with smoking abstinence at week 12 as the primary endpoint. AXS-05's dual NMDA/sigma-1 mechanism differentiates it from nicotinic-receptor-targeted approaches like cytisinicline and varenicline. If SUMMIT data are supportive, there may be potential for a mechanistically distinct option for the roughly 34 million US adults who smoke.

References

1. McIntyre RS, Zhang-James Y, Kwan ATH. Glucagon-like peptide 1 receptor agonists, mortality, and cardiovascular outcomes in serious mental illness. JAMA Psychiatry. August 26, 2026. Accessed August 31, 2026.

2. Zhou Y, Postmus D, Hartman CA, et al. Long-term cardiorenal illness trajectories after initiation of antihypertensive medications in adults with and without ADHD: a nationwide cohort study. Nat Ment Health. August 31, 2026. Accessed August 31, 2026.

3. Axsome Therapeutics initiates SUMMIT Phase 3 trial of AXS-05 in smoking cessation. Press release. August 31, 2026. Accessed August 31, 2026. https://www.globenewswire.com/news-release/2026/08/31/3353172/33090/en/axsome-therapeutics-initiates-summit-phase-3-trial-of-axs-05-in-smoking-cessation.html

4. APSARD announces launch of final review stage for US Adult ADHD Guidelines; publication anticipated this fall. Press release. August 28, 2026.

5. Meta settles landmark state child harm claims for $18 billion and promises changes to its platforms. CNN. August 26, 2026. Accessed August 31, 2026. https://www.cnn.com/2026/08/26/tech/meta-states-settle-trial-children