Opparounds

Ketamine Infusions and Rapid Reduction of Suicidal and Depressive Symptoms in Major Depressive Episode: A Systematic Review and Meta-Analysis

Sung Ryul Shim, Hye Su Jeong, Tanner J. Bommersbach, Andrew A. Nierenberg, Carlos A. Zarate Jr, Tyler S. Kaster, Christoph U. Correll, Roger S. McIntyre, John H. Krystal, Taeho Greg Rhee · JAMA Psychiatry · May 2026

This meta-analysis pooled 26 randomized controlled trials (1,166 patients with a major depressive episode, including MDD and bipolar depression) comparing intravenous ketamine infusions against saline or midazolam control. Depressive symptoms improved fastest at 4 hours post-infusion (SMD −1.74) and remained significantly reduced through 1 week and after a full course of repeated infusions.

Suicidal ideation also dropped significantly by 24 hours (SMD −0.69), with the benefit still present at 1 month, and single and repeated dosing showed comparable effect sizes. Serious adverse events attributed to ketamine itself were rare, though most trials only followed patients for hours to days, so durability beyond a month is still unclear.

Read the paper →  doi:10.1001/jamapsychiatry.2026.0612

Is More Treatment Truly Better? A Meta-Analysis of the Dose-Response Effect of Individual Psychotherapy for Treatment of Generalized Anxiety Disorder in Adults

D. Drew Whittington, Rachel Billings, Louis A. Pagano Jr, Stephen L. Aita, Jacob Vaughn, Samuel D. Spencer, Nicholas C. Borgogna · Journal of Cognitive Psychotherapy · July 2026

This preregistered meta-analysis pooled 41 randomized trials of individual psychotherapy for adult GAD (1,607 participants) to test whether more treatment produces better outcomes. Using meta-regression, neither total therapy duration nor number of sessions predicted greater symptom reduction, and total therapist contact time showed only a trivial relationship to outcome.

The one dose variable that mattered was session length: trials using sessions longer than 60 minutes produced significantly larger effects than trials using shorter sessions. The authors note this held up across several moderating variables, though the study can't say whether the extra minutes are doing the work or simply correlate with therapists who structure sessions differently.

Read the paper →  doi:10.1891/JCP-2025-0053

T3 Augmentation Works Faster Than T4 Because It Skips a Step

Levothyroxine (T4) is a prohormone: it has to be converted to T3 by peripheral and central deiodinases before it can do anything to mood circuitry. In treatment-resistant depression, that conversion step is exactly where things can stall — deiodinase activity is downregulated by chronic stress and by some of the same inflammatory pathways implicated in TRD.

Liothyronine (T3) bypasses the bottleneck entirely: it crosses the blood-brain barrier unconverted and binds nuclear thyroid receptor beta directly, where it modulates transcription of serotonergic and noradrenergic target genes. That's the pharmacologic reason STAR*D found T3 augmentation as effective as lithium augmentation with a cleaner side-effect profile — no need to titrate to a serum level, no renal monitoring.

Practically: start 25 mcg/day, titrate to 50 mcg over 1–2 weeks, and expect a response window of days, not the 4–6 weeks you'd wait out on an SSRI switch. Check TSH before starting and periodically after — mild iatrogenic hyperthyroidism is the main risk, and it matters more than usual in patients with any cardiac history, since T3 given directly, unlike T4, cannot be buffered by the body's own conversion rate.

Container-Contained: The Anxiety Has to Land Somewhere Before It Can Be Thought

Bion's container-contained model reframes projective identification as communication before it's pathology: an infant (or patient) evacuates an intolerable state — raw, unformed 'beta elements' — into someone else because it cannot yet be thought, only felt and expelled. The container's job isn't to interpret it back immediately. It's reverie: tolerating the unprocessed feeling long enough to metabolize it into something nameable ('alpha elements'), then handing it back in a form the patient can actually use.

The technique isn't validation and it isn't insight — it's surviving the projection without retaliating, collapsing, or prematurely explaining it away. A therapist who interprets too fast is often defending against having to hold the feeling at all, which is itself a failure to contain. The measure of good containing is whether the patient leaves more able to think about the feeling than they were able to when they walked in.