Friday, August 28, 2026

Opparounds

🔬Psychiatric Research Article

Use and Misuse of GLP-1 Receptor Agonists Among People With Eating Disorders

Nicholas C. Peiper, Jon E. Zibbell, Andrew S. LaJoie, Banrida Wahlang, Sathya S. Krishnasamy, Cheri A. Levinson · JAMA Psychiatry · June 2026

This research letter surveyed 436 US adults with eating disorders and found substantial GLP-1 receptor agonist (GLP-1 RA) exposure: 32.1% reported lifetime use and 22.0% reported current use, both well above the roughly 15% lifetime-use rate in the general adult population. 10.1% reported lifetime misuse — using the medication in ways that served restriction rather than the prescribed indication — and 9.9% reported using compounded, non-FDA-regulated products, a category that has grown alongside shortages of the branded agents.

Use was highest among those with binge-eating disorder and lowest among those with anorexia nervosa, and psychiatric comorbidity was the norm in this sample: 87.5% had a comorbid anxiety disorder and 70.8% a comorbid mood disorder.

💡 Why it matters

A GLP-1 RA prescription — or a self-sourced compounded product — in a patient with an eating disorder history deserves the same scrutiny as any other appetite-suppressing agent; screen for it explicitly, since patients may not volunteer use they suspect you'd discourage.

Read the paper → doi:10.1001/jamapsychiatry.2026.1716

🩺General Medicine Article

Depression and Anxiety Associate With Adverse Cardiovascular Events via Neural, Autonomic, and Inflammatory Pathways

Shady Abohashem, Ahmed Tawakol, et al. · Circulation: Cardiovascular Imaging · December 2025

In this Mass General Brigham Biobank cohort of 85,551 adults — 14,934 with comorbid depression and anxiety, 15,819 with either alone, and 54,798 with neither — followed for a median of 3.4 years, having both depression and anxiety carried roughly a 32% higher risk of major adverse cardiovascular events (3,078 total events) than having either condition alone. Mediation analysis attributed a meaningful share of that excess risk to three measurable pathways: heightened amygdala-to-cortex activity on brain imaging, reduced heart rate variability, and elevated CRP — the neural-stress, autonomic, and inflammatory axes long hypothesized to connect mood and cardiovascular disease. The associations held after adjusting for traditional cardiac risk factors and health behaviors.

💡 Why it matters

Untreated comorbid depression and anxiety functions as a measurable cardiac risk factor in its own right — one more reason to treat the anxiety, not just the mood episode, and to loop in primary care or cardiology when both are present.

Read the paper → doi:10.1161/CIRCIMAGING.124.017706

💊Psychiatric Fact

Methadone's QTc risk is a genotype problem, not just a dose problem

Methadone is a racemic mixture, and its two enantiomers do very different jobs: R-methadone carries essentially all the mu-opioid analgesic and withdrawal-suppressing activity, while S-methadone is the one that blocks the cardiac hERG potassium channel and drives QTc prolongation. CYP2B6 clears S-methadone preferentially, and roughly 4-6% of patients are CYP2B6 poor metabolizers who accumulate S-methadone disproportionately to R-methadone — so two patients on an identical daily dose can carry very different QTc exposure depending on genotype alone.

This is why QTc prolongation doesn't reliably track total daily dose in cohort data, and why a patient stable on methadone for years can still develop a prolonged QTc with no dose change if a CYP2B6 or CYP3A4 inhibitor (fluconazole, fluvoxamine) is added. Practical implication: get a baseline and follow-up ECG regardless of dose, and treat any new interacting medication — not just a dose increase — as a reason to recheck the QTc.

🛋️Psychotherapy Teaching Pearl

Symbolic equation: when the metaphor stops being a metaphor

Hanna Segal's distinction between symbolic equation and true symbol formation describes two different relationships a patient can have to language. In symbol formation, the symbol represents the object while staying recognizably separate from it — a dream about being devoured is understood as *about* something. In symbolic equation, that gap collapses: the symbol *is* the object, concretely, without the "as-if." A patient functioning this way doesn't hear your interpretation as a perspective on their experience — they experience it as the literal event itself.

This isn't a stylistic quirk; it tracks with more primitive, often psychotic-level organization, and it changes technique. Interpreting the unconscious meaning of a symbolically-equated communication doesn't produce insight — it re-traumatizes, because the patient has no symbolic distance to receive it from. The task is first to build that distance, not to interpret through it.

🗒️ Vignette

A patient with psychotic-level organization tells her therapist, "You said I'm empty inside" — a comment the therapist never made; she had said the patient described feeling "like there's nothing there some days." That night the patient binged until she vomited, saying afterward she'd needed to "fill the emptiness you pointed out."

The therapist resisted the pull to clarify what she'd *really* meant — a move that assumes the patient can already hear it as perspective — and instead named the collapse directly: "When I said 'nothing there,' it became a fact about you, not a description, and then your body had to do something about that fact." Only after several sessions of naming the concreteness itself, rather than interpreting its content, did the patient begin reporting interpretations as ideas rather than events.

📰In the News

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The FDA's August 5, 2026 approval of oveporexton (Orzeyful), the first orexin-2 receptor agonist for narcolepsy type 1, directly replaces the missing neuropeptide rather than just promoting wakefulness — worth knowing since narcolepsy is routinely misread as depression or ADHD before cataplexy is recognized. source →

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The FDA's late-July 2026 approval of centanafadine (Simtriyo) gives ADHD a genuinely new mechanism — a norepinephrine-dopamine-serotonin reuptake inhibitor, not a stimulant — but it carries its own boxed warning for pediatric suicidality and stimulant-like abuse potential. source →