Opparounds

Effects of Brexpiprazole on Functioning in Patients With Schizophrenia Who Have Hostility and Agitation Symptoms: Post Hoc Analysis of Short- and Long-Term Trials

Citrome L, Farovik A, Palma AM, Yildirim M · Journal of Clinical Psychiatry · July 2026

This post hoc analysis pooled short-term data from three 6-week, randomized, double-blind, placebo-controlled trials of brexpiprazole in acute schizophrenia (n=1,385 analyzed; 692 with baseline hostility per PANSS item P7, 784 with baseline agitation per the PANSS-Excited Component), plus long-term data from two 52-week open-label extensions (n=408). The question was whether brexpiprazole still improves real-world functioning, measured by the Personal and Social Performance (PSP) scale, in patients whose presentation includes hostility or agitation — symptoms clinicians sometimes treat as a reason to reach for something more sedating instead.

At Week 6, brexpiprazole (2–4 mg/day) produced significantly greater PSP improvement than placebo in both the hostility subgroup (+2.82 points, P=.014) and the agitation subgroup (+4.05 points, P<.001) — the agitation subgroup actually showed the larger effect. Gains continued through the open-label extensions, with functional response rates of 90.6% at Week 58 for the hostility subgroup and 77.5% for the agitation subgroup.

Read the paper →  doi:10.4088/JCP.26m16448

Effects of Perceived Working Alliance Quality and Congruence on Naturalistic Psychotherapy Outcome: A Response Surface Analysis

Fanny Alexandra Dietel, Ivo Georgiev, Julia Müller, Tanja Andor, Isabelle Drenckhan, Julienne Seidemann, Heinz Holling, Nexhmedin Morina, Ulrike Buhlmann · Psychotherapy Research · August 2026

In a naturalistic sample of 353 outpatients receiving CBT and their 95 therapists, both parties rated the working alliance early in treatment. Rather than collapsing patient and therapist ratings into a single discrepancy score — which throws away information about whether both raters were high, both low, or split — the authors used response surface analysis to model alliance level and patient-therapist congruence as separate predictors of later depression, distress, and quality-of-life outcomes.

Therapist-rated alliance, not patient-rated alliance, predicted better outcomes. Congruence between the two ratings added nothing once alliance level was accounted for — there was no penalty for the two parties seeing the relationship differently, only a benefit when the therapist rated it highly. The pattern held after controlling for total session count.

Read the paper →  doi:10.1080/10503307.2025.2553636

Gabapentin's dose-response curve bends because its absorption does

Gabapentin isn't absorbed by passive diffusion — it crosses the gut wall via the saturable LAT1 amino-acid transporter, the same carrier that moves phenylalanine and leucine. That transporter has a fixed capacity, so as the dose climbs, bioavailability falls: roughly 60% at 900 mg/day but closer to 33% by 3,600 mg/day. Doubling the dose from 1,800 to 3,600 mg does not double serum exposure — it adds only a fraction of what the first 1,800 mg contributed.

Pregabalin, by contrast, crosses passively and has linear, dose-proportional kinetics across its range. The clinical implication: if a patient plateaus on high-dose gabapentin for anxiety, neuropathic pain, or alcohol-withdrawal prophylaxis, pushing the dose further is chasing a diminishing return, not correcting an underdose. Splitting the daily dose into more frequent intervals (to reduce the per-dose transporter load) or switching to pregabalin is more likely to move the needle than another increase.

Irreverence is a calculated destabilization, not sarcasm

DBT names two communication styles a therapist moves between: reciprocal communication — warmth, self-disclosure, responsiveness — and irreverent communication, which deliberately unbalances the patient by responding in a way they don't expect. Irreverence isn't wit for its own sake. It's reserved for moments when reciprocal warmth would reinforce a maladaptive pattern: a guilt-inducing dropout threat, a rigid catastrophic narrative, a request that's really testing whether the therapist will rescue.

A flat, matter-of-fact, slightly off-script response interrupts the expected sequence and forces the patient to re-engage with what they actually want, rather than the script they're running. It only works from a secure alliance — attempted without one, it reads as dismissive rather than disruptive — and it is almost always followed immediately by a return to warmth, so the patient experiences a jolt, not a rejection.