Morning Rounds: September 1-8
Key Takeaways
- Serial, flexibly dosed ketamine infusions (0.5–0.75 mg/kg) over 2 weeks reduced MADRS by 7.3 points versus midazolam, meeting prespecified clinical significance and showing a moderate effect size (d=0.7).
- Safety signals in Ket-BD included no treatment-emergent mania, hypomania, or psychosis, addressing a central barrier to controlled ketamine evidence in bipolar depression.
Catch up on psychiatry news from last week.
Clinical Research
IV Ketamine Shows Antidepressant Benefit in Treatment-Resistant Bipolar Depression
Adjunctive intravenous (IV) ketamine produced significantly greater reductions in depressive symptoms than midazolam among adults with treatment-resistant bipolar I or II depression, according to results from the Ket-BD randomized clinical trial.¹ The double-blind, midazolam-controlled trial enrolled 68 participants across 3 sites in Canada, randomizing them 1:1 to 4 flexibly dosed, 40-minute infusions of ketamine (0.5-0.75 mg/kg) or midazolam (0.02-0.03 mg/kg) over 2 weeks, added to a stable mood stabilizer or antipsychotic regimen.¹ At day 14, MADRS scores were 7.3 points lower with ketamine than with midazolam (95% CI: -12.0 to -2.5; P = 0.003; Cohen d=0.7), exceeding the prespecified threshold for clinical significance.¹ No cases of treatment-emergent mania, hypomania, or psychosis occurred in either arm. Bipolar depression has historically been underrepresented in ketamine research because of concerns about triggering mood destabilization, leaving prescribers with little controlled evidence to guide off-label use in this population. For psychiatrists managing treatment resistant bipolar disorder, the findings support considering adjunctive IV ketamine in carefully selected patients who have failed guideline-recommended first-line treatments, with continued monitoring for dissociative and hypomanic symptoms during infusions.
Pharmaceutical Updates
FDA Grants Second Breakthrough Therapy Designation to DT120 for Major Depressive Disorder
The US Food and Drug Administration has granted Breakthrough Therapy designation to Definium Therapeutics for DT120 (lysergide) orally disintegrating tablet (ODT) for major depressive disorder (MDD), the company's second such designation for the drug.² The designation was supported by phase 3 Emerge study results, in which a single 100-µg dose of DT120 ODT produced a statistically significant 8.1-point placebo-adjusted improvement in MADRS total score at week 6 (P < 0.0001), with durable efficacy through week 12.² DT120 ODT, the tartrate salt form of lysergide, is an ergoline-derived, classic serotonergic psychedelic acting as a partial 5-HT2A receptor agonist, formulated with fast-dissolve technology intended to improve absorption onset and bioavailability relative to earlier LSD formulations.² The drug's first Breakthrough Therapy designation, granted for generalized anxiety disorder, was based on the phase 3 Voyage trial, in which benefits emerged within days of a single dose and persisted through 12 weeks.²
Policy & Legislation
Bipartisan Bill Would Direct VA to Expand Veteran Access to Vet Center Mental Health Counseling
A bill has been recently introduced for the Veterans Centers-Enabled National Treatment Equitable Resource Supplement (CENTERS) for Mental Health Act of 2026.3 The bill would direct the Department of Veterans Affairs to use census data and its own statistical data to ensure every veteran has reasonable access to a Vet Center.3 Vet Centers provide mental health counseling to combat veterans and survivors of military sexual trauma, as well as bereavement services to families of service members who die on duty, a family-inclusive service model that is distinct within the VA care system. Sponsors cited long travel distances and understaffed centers in rural areas, particularly in Washington state, as key access barriers driving the legislation. The bill has not yet been scheduled for committee action. Passage could expand the geographic footprint of VA-affiliated counseling resources and ease referral bottlenecks for patients in underserved or rural areas.
References
1. Orsini DK, Di Luch S, Tomlinson G, et al.
2. Definium Therapeutics receives Breakthrough Therapy designation for DT120 (lysergide) orally disintegrating tablet (ODT) in major depressive disorder (MDD) following positive phase 3 results. Press release. September 8, 2026. Accessed September 8, 2026.
3. Kean introduces bipartisan legislation to expand access to veteran mental health services. Press release. September 1, 2026. Accessed September 8, 2026.
