Opparounds

Impact of Vagus Nerve Stimulation on Suicidal Ideation in Markedly Treatment-Resistant Major Depression: A RECOVER Study Report

Vasilis C. Hristidis, Victoria De Leon, Andrew D. Van Der Vaart, et al. · The Journal of Clinical Psychiatry · July 2026

This RECOVER trial secondary analysis randomized 463 adults with markedly treatment-resistant major depression -- all with at least four failed antidepressant trials -- to adjunctive active or sham vagus nerve stimulation plus treatment as usual for 12 months. Active VNS produced significantly greater odds of meaningful improvement in suicidal ideation than sham (OR 1.43) and significantly higher remission rates in months 10-12 (OR 1.67), even though the trial's primary depression-severity endpoint narrowly missed significance because of an unexpectedly strong sham response. VNS did not worsen ideation or provoke new suicidal thoughts in participants who started without any. The ideation benefit built gradually across the year rather than appearing early, consistent with VNS's known slow onset.

Read the paper →  doi:10.4088/JCP.25m16296

Acute Effects of Cannabis Inhalation on Cardiac Ectopy, Physical Activity, Sleep, and Glucose

Alexander Elias, Gabriel C. Montenegro, Hnin H. Oo, et al. · Journal of the American College of Cardiology (JACC) · July 2026

In a 14-day randomized crossover trial, 108 regular cannabis users with no history of arrhythmia wore continuous cardiac monitors while being randomized day by day to inhale cannabis or abstain, yielding 713 use-days and 616 abstinence-days. Contrary to the usual assumption that cannabis acutely provokes arrhythmia, use-days showed 9 to 10 percent fewer premature atrial contractions than abstinence days, with no significant difference in ventricular ectopy, step counts, sleep duration, or glucose. The authors caution that imperfect adherence, carryover effects, and low baseline ectopy limit how far the finding should travel, and the trial says nothing about the cardiovascular risk of regular, chronic use.

Read the paper →  doi:10.1016/j.jacc.2026.07.014

Paliperidone Palmitate's Depot Math Breaks Down Below a CrCl of 50

Oral risperidone is cleared hepatically via CYP2D6, but its long-acting injectable form releases paliperidone, which is eliminated almost entirely by the kidney -- roughly 80 percent unchanged in urine. That single fact rewrites how the depot has to be dosed. For a CrCl of 50 to under 80 mL/min, the label doesn't ask for a small trim: the once-monthly formulation starts lower (156 mg on day 1, 117 mg on day 8) and caps out at a maximum monthly maintenance dose of 156 mg, well below the ceiling allowed with normal renal function. Below a CrCl of 50, the once-monthly IM formulation isn't recommended at all -- not because the drug stops working, but because a depot can't be titrated down quickly once it's injected. If renal function declines silently between injections, there's no oral dose you can just skip to compensate; the drug is already in the muscle, releasing on its own schedule for weeks. That's the practical reason to recheck renal function on this depot at the same cadence you'd recheck a lithium level in an older or medically frail patient, not just at intake.

Not All Validation Is the Same Intervention

Linehan described six levels of validation, and the number matters because residents tend to collapse them into one move: reflect the feeling. Level 1 is simply staying present and attentive. Level 2 is accurate reflection -- saying back what you heard. Level 3 is articulating what the patient hasn't said yet: the emotion or thought implied by their words but never spoken aloud. Level 4 validates the response as making sense given the patient's learning history, even when it isn't accurate to the current situation. Level 5 validates it as reasonable given the current context -- not just understandable, but actually warranted. Level 6, radical genuineness, treats the patient as a capable equal rather than someone too fragile for the therapist's honest reaction. The technical error isn't skipping validation; it's jumping straight to level 5 or 6 before level 3 has done its work of naming what's actually underneath the urge.