Opparounds

Connectivity- vs Scalp-Based Targeting of Accelerated Transcranial Magnetic Stimulation for Depression: A Randomized Clinical Trial

Joseph J. Taylor, Marina R. Kare, Dania Haj-Darwish, et al. · JAMA Psychiatry · June 2026

This trial randomized 40 adults with treatment-resistant major depressive disorder undergoing accelerated, SAINT-style TMS to one of two ways of choosing the stimulation site: an individualized target derived from each patient's own resting-state fMRI connectivity to a depression-linked circuit, or the conventional scalp-landmark target (Beam F3). Every participant underwent the same connectivity scan at baseline, but only the connectivity-guided arm actually had treatment steered by it.

At one month, the connectivity-guided group had a substantially larger drop in depression severity than the scalp-targeted group, with a median MADRS reduction of 24 points versus 18 points, and a higher response rate, 80% versus 60%. The effect size favoring individualized targeting was large (d = 0.8), with a number needed to scan of five.

Read the paper →  doi:10.1001/jamapsychiatry.2026.1100

A 14-Month Randomized Clinical Trial of Treatment Strategies for Attention-Deficit/Hyperactivity Disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD

MTA Cooperative Group · Archives of General Psychiatry · December 1999

The MTA trial randomized 579 children aged 7 to 9.9 with ADHD Combined Type to 14 months of one of four strategies: intensive, closely titrated medication management; intensive behavioral treatment (parent, school, and child components); the combination of both; or routine community care, which for most participants also included medication, just less rigorously managed.

For core ADHD symptoms, carefully titrated medication management outperformed behavioral treatment alone and typical community care, even though community care often included the same medications — the difference was in how the medication was managed, not just whether it was prescribed. Combined treatment was not significantly better than medication management on core symptoms, but showed added benefit on oppositional and internalizing symptoms, parent-child relations, and academic measures, and reached comparable core-symptom control at somewhat lower average doses.

Read the paper →  doi:10.1001/archpsyc.56.12.1073

Lisdexamfetamine's abuse-deterrence lives in the blood, not the liver

Lisdexamfetamine is an inactive prodrug — l-lysine conjugated to dextroamphetamine — and it can't do anything until that bond is cleaved. That cleavage happens mainly through enzymatic hydrolysis by red blood cell peptidases, not first-pass hepatic metabolism, and the distinction changes three things a resident is likely to get asked about.

First, the abuse-deterrent property is real and mechanistic: chewing, snorting, or injecting the intact molecule doesn't speed onset, because the rate-limiting step is hydrolysis in blood, not absorption. Second, hepatic impairment does not meaningfully change amphetamine exposure from lisdexamfetamine, so unlike most psychotropics, no hepatic dose adjustment is needed — worth knowing before reflexively lowering the starting dose in a patient with cirrhosis. Third, renal impairment does slow clearance of the liberated dextroamphetamine, so renal dosing adjustment is the one that actually applies, the opposite of what most clinicians instinctively reach for. When switching a patient between lisdexamfetamine and a mixed amphetamine salt product, remember the rate-limiting step itself differs, not just the release mechanism.

Contract-setting is the intervention before the interpretation

In TFP, the pre-treatment contract isn't paperwork — it's the first technical structure that makes exploratory work possible at all. Before clarification-confrontation-interpretation work can begin, therapist and patient explicitly negotiate the concrete conditions most likely to interrupt treatment: what happens around self-harm, missed sessions, substance use, or that particular patient's own documented history of derailing care.

The technical function is to convert unpredictable crises into named, anticipated events the pair already has shared language for — so that when the predictable thing happens, it becomes material to be understood together rather than an emergency the therapist has to manage alone, reactively, outside the frame. A contract that's just a list of clinic rules hasn't done this work. A contract that names the patient's own history of undermining treatment, in the patient's own words, has.