Opparounds

Antipsychotic Efficacy and Safety of LB-102 in the Treatment of Adults With Acute Schizophrenia: A Randomized Clinical Trial

Eramo A, Correll CU, Walling DP, et al. · JAMA Psychiatry · April 2026

This phase 2, double-blind, placebo-controlled trial (NOVA-1) randomized 359 adults with acute schizophrenia to placebo or once-daily LB-102 — a D2/D3/5-HT7 antagonist that is the active N-methyl metabolite of amisulpride — at 50, 75, or 100 mg for 4 weeks.

Both the 50 mg and 75 mg arms produced significantly greater reductions in PANSS total score than placebo (roughly 14 points versus 9.3, P<.001 and P=.002). Treatment-emergent adverse events occurred in 56–75% of participants, but extrapyramidal symptoms stayed low across every dose. Weight gain over just 4 weeks averaged 4.3 kg on 50 mg versus 2.1 kg on placebo, and prolactin elevation was common, though rarely symptomatic.

Read the paper →  doi:10.1001/jamapsychiatry.2026.0428

Neuropsychiatric Outcomes With Tirzepatide, Semaglutide, and Other GLP-1 Receptor Agonists

Chen SC-C, Wang T-J, Chou C-K, Lee C · Diabetes, Obesity & Metabolism · July 2026

Using the TriNetX global federated network (over 192 million patients), this retrospective new-user cohort study compared psychiatric outcomes among adults with type 2 diabetes or obesity who started tirzepatide, semaglutide, or an earlier-generation GLP-1 receptor agonist between 2022 and 2025.

After propensity-score matching (over 85,000 pairs per comparison), Cox models found tirzepatide and semaglutide had comparable neuropsychiatric risk profiles over 2 years of follow-up. But semaglutide showed significantly lower first-year rates of depression, anxiety, and suicidal ideation than older-generation GLP-1 agents.

Read the paper →  doi:10.1111/dom.71088

Normal ammonia isn't reassuring, and normal LFTs never rule out valproate hyperammonemia

Valproate-induced hyperammonemic encephalopathy (VHE) doesn't need a supratherapeutic level, an abnormal LFT, or a low carnitine to happen — documented cases occur at therapeutic valproate concentrations with entirely normal transaminases and normal serum carnitine. The mechanism sits upstream of the liver: valproate's mitochondrial metabolites (propionyl-CoA and valproyl-CoA) inhibit N-acetylglutamate synthetase, the enzyme that primes the urea cycle's rate-limiting step. Ammonia backs up regardless of what the liver panel shows, crosses into the brain, and drives astrocyte swelling — which is why the presentation is disproportionate lethargy, confusion, or new cognitive slowing rather than anything resembling classic hepatotoxicity.

The practical move: if a patient on valproate develops unexplained sedation or slowed cognition, check an ammonia level regardless of a normal LFT or therapeutic drug level, and don't wait on a carnitine result before treating. Levocarnitine is first-line even when serum carnitine is normal, because it works by shifting valproate metabolism away from the ammoniagenic pathway — not by correcting a deficiency.

Triangulation isn't the problem — it's the map of who's not differentiated

In Bowen family systems theory, a dyad under anxiety recruits a third party — a triangle — not primarily to gang up, but to diffuse tension neither person can hold alone. The triangle is stable precisely because it works: pulling in a third lowers anxiety in the twosome, which is why the pattern re-forms every time a third party is removed without any change in the underlying differentiation of self — the capacity to stay emotionally connected to others while holding a separate, thought-out position under pressure.

Low-differentiation systems don't triangulate a spouse, a child, or a therapist by accident; they do it because someone in the dyad can't self-soothe without borrowing the third party's attention, alliance, or blame. The technical task isn't to break the triangle by fiat — banning triangulating talk — it's to help the most anxious member tolerate the original dyad's tension directly, which is slower and far more durable.