Opparounds

Neurometabolites and Antipsychotic Response in Psychosis: A Mega-Analysis

King B, Bojesen KB, Crisp C, et al. · JAMA Psychiatry · September 2026

This mega-analysis pooled individual participant-level proton MRS data from 1,189 people across 18 studies -- 476 antipsychotic nonresponders, 427 responders, and 286 healthy controls -- to look for a neurochemical signature of treatment resistance.

Compared with responders, nonresponders showed higher medial frontal glutamate, glutamate-plus-glutamine, choline, and myo-inositol, with the largest myo-inositol elevations concentrated in treatment-resistant patients specifically. In a prospective subset, elevated medial frontal glutamate-plus-glutamine measured early in a first episode predicted a worse two-year course -- meaning the signal is present before resistance is clinically obvious, not just after repeated drug trials.

Read the paper →  doi:10.1001/jamapsychiatry.2026.1674

The Effect of Fluvoxamine and Metformin for Fatigue in Patients With Long COVID: An Adaptive Randomized Trial

Reis G, dos Santos Moreira Silva EA, Medeiros Silva DC, et al; REVIVE Investigators · Annals of Internal Medicine · May 2026

This adaptive, placebo-controlled trial randomized 399 adults with fatigue persisting 90 or more days after confirmed SARS-CoV-2 infection, across 22 Brazilian outpatient sites, to fluvoxamine 100 mg twice daily, metformin 750 mg twice daily, or placebo for 60 days.

Fluvoxamine produced a significant reduction in fatigue versus placebo by day 60 that was sustained at day 90, while metformin showed no benefit and was dropped for futility partway through. The trial did not separately assess baseline depression, so whether fluvoxamine worked through its anti-inflammatory sigma-1 agonism, a direct antidepressant effect, or both remains genuinely unclear from this data.

Read the paper →  doi:10.7326/ANNALS-25-03959

Bupropion's CYP2D6 Inhibition Can Quietly Undo Tamoxifen

Bupropion is one of the most potent CYP2D6 inhibitors used in psychiatry, and the inhibition is dose-dependent, starting within days of initiation and reaching its full effect within one to two weeks -- well before most clinicians reassess a new antidepressant. The problem surfaces specifically in patients on tamoxifen, which needs CYP2D6 to convert to its active metabolite, endoxifen.

Co-administering bupropion can cut endoxifen concentrations by roughly 50 to 75 percent, silently undermining adjuvant breast cancer therapy without producing any symptom that would flag the interaction -- the patient feels fine, the oncologist sees a normal visit, and nothing looks wrong until a recurrence years later raises the question retrospectively. If a patient on tamoxifen needs an antidepressant, an agent with minimal CYP2D6 inhibition -- sertraline, citalopram, escitalopram, or venlafaxine -- is the safer default; bupropion and paroxetine are the two to actively avoid.

Communication Analysis Finds the Gap Insight Alone Can't

IPT's communication analysis is not "how did that conversation go" -- it is a line-by-line reconstruction of a single recent, affectively loaded exchange, asking what the patient actually said, what they intended, and where the two diverged.

Depressed patients systematically underperform their own intentions in close relationships: they mean to ask for help and instead go silent, mean to set a limit and instead over-apologize, mean to grieve a role transition openly and instead perform competence. The technique's value is that it locates the mechanism concretely, in a scene, rather than in a trait -- "you're avoidant" teaches nothing, but naming the exact moment silence was chosen instead gives the patient something to actually do differently next time. It is technique, not insight for its own sake -- the point is a rehearsed alternative, not a realization.