Opparounds

Mirtazapine for Methamphetamine Use Disorder: A Randomized Clinical Trial

Rebecca McKetin, Steven Shoptaw, Lucy Saunders, Long Nguyen, Philip J. Clare, Gregory J. Dore, Alyna Turner, Olivia M. Dean, Peter J. Kelly, Shalini Arunogiri, et al. · JAMA Psychiatry · June 2026

Unlike most addiction pharmacotherapy trials run under tightly controlled research conditions, this phase 3 trial tested mirtazapine (30 mg/day for 12 weeks) versus placebo for methamphetamine use disorder inside 6 ordinary Australian outpatient addiction clinics — 339 participants, prescribed and monitored as part of routine care rather than a specialty research protocol. Participants averaged 24 days of methamphetamine use in the month before enrollment.

Mirtazapine reduced days of use by 7.0 versus 4.8 with placebo (difference −2.2 days; 95% CI, −4.2 to −0.2; P=.02). Drowsiness (47% vs 33%) and weight gain (10% vs 3%) were more common with mirtazapine, and discontinuation for adverse events was somewhat higher (23% vs 15%), but no unexpected safety signal emerged. Secondary measures — depression, insomnia, HIV risk behavior, quality of life — didn't differ significantly between arms.

Read the paper →  doi:10.1001/jamapsychiatry.2026.0159

Mechanisms of Change in Day Treatment Group Schema Therapy for Severe Personality Disorders: A Multiple Baseline Single-Case Study

Joska van Houten, Samantha Bouwmeester, Nathan Bachrach · Clinical Psychology & Psychotherapy · May 2026

This study asked a mechanism question schema therapy hasn't fully answered: which of its own theorized ingredients actually drives symptom change? Using a multiple-baseline single-case design, patients with severe personality disorders in day-treatment group schema therapy had personality disorder severity assessed before and after treatment, while negative core beliefs and schema-mode activity were tracked weekly across 30 weeks.

Changes in personality disorder severity moderately correlated with changes in negative core beliefs (r = 0.57) but did not track meaningfully with change in schema modes — suggesting the beliefs themselves, not the mode-shifting framework built on top of them, may be doing more of the actual work. The authors argue treatment should prioritize reducing activation of the Vulnerable Child mode and its associated early maladaptive schemas, while reinforcing Healthy Adult and Happy Child modes.

Read the paper →  doi:10.1002/cpp.70289

Extended-release naltrexone's real danger window opens after treatment, not during induction

Starting XR-naltrexone safely requires confirming the patient is truly opioid-free — typically 7 to 10 days after short-acting opioids, longer after methadone or high-dose buprenorphine — often verified with a naloxone challenge before the first injection, since starting too early precipitates withdrawal. That part gets taught. The part that gets taught less is the more dangerous window: naltrexone blocks opioid effects completely, so physiological tolerance falls during treatment, and a patient who resumes use after a missed injection or after stopping — whether relapse or simply discontinuing — returns to a dose their body can no longer handle.

This is the same tolerance-loss mechanism behind the well-documented spike in overdose deaths after detox and after incarceration. It means discharge planning matters as much as induction technique: every naltrexone start deserves an explicit conversation about overdose risk if use resumes, and naloxone in the patient's hands before they leave, not just a clean induction on the way in.

In TFP, naming the dyad is the intervention — not just diagnosing splitting

Identifying "splitting" as a defense is only half of TFP's technique; the more specific move is naming which object-relations dyad is active in the room right now — a self-representation and an other-representation paired with an affect, such as helpless-victim/all-powerful-persecutor, or entitled-child/depriving-authority. Patients with identity diffusion don't experience these as concepts; they experience them as reality, fully occupying one role while the therapist is unconsciously assigned the other — and the dyad can flip without warning as the underlying projective mechanisms shift.

TFP technique doesn't wait to interpret the deep origin of the pattern; it names the dyad as it's happening — who is being cast as what, and what affect is organizing it. This does two things at once: it gives identity diffusion a concrete, sayable shape instead of a vague sense of chaos, and it interrupts the enactment by making it explicit before the therapist has fully complied with the assigned role.