Q3 2025 Recap: Psychiatry News and Updates

As Q3 2025 comes to a close, HCPLive reviews notable advances in psychiatry, highlighting regulatory updates, emerging therapies, and key clinical trial findings. Clinicians have seen the FDA propose an acetaminophen label change, advance leucovorin approval for cerebral folate deficiency, grant Fast Track and Breakthrough Therapy designations for NRX-100 and TSND-201, and review lumateperone for schizophrenia relapse prevention. Phase 2 and 3 data from trials of MM120, ammoxetine, and RE104 offer promising options for generalized anxiety disorder, major depressive disorder, and postpartum depression, reflecting evolving treatment strategies.

Q3 2025 Regulatory Updates in Psychiatry

FDA Initiates Acetaminophen Label Change, Leucovorin Approval for Cerebral Folate

The FDA proposed updating acetaminophen labeling to inform parents and clinicians of potential neurological risks linked to prenatal use, including autism and ADHD. At the same time, the agency is advancing leucovorin calcium (Wellcovorin) approval for cerebral folate deficiency, a rare disorder associated with developmental delays, seizures, and autistic features.

Related:

• APhA, Coalition of Autism Scientists Cite Insufficient Data to Support Acetaminophen, Autism Link
• ACOG, AAP Respond to White House Autism Announcements on Acetaminophen, Leucovorin

FDA Grants NRX-100 Fast Track Designation for Suicidal Ideation

The FDA has granted Fast Track Designation to NRX-100, a preservative-free intravenous ketamine, for the treatment of suicidal ideation in patients with depression, including bipolar depression. Developed by NRx Pharmaceuticals, NRX-100 has shown significant reductions in suicidal thoughts across multiple clinical trials, with results demonstrating superiority over placebo and active comparators. Studies reported rapid response rates, with more than half of patients achieving meaningful improvement within days.

FDA Grants TSND-201 Breakthrough Therapy Designation for PTSD

The FDA has granted Breakthrough Therapy designation to TSND-201 (methylone), a rapid-acting neuropathogen developed by Transcend Therapeutics for the treatment of PTSD. Unlike hallucinogenic agents, TSND-201 targets monoamine transporters without 5-HT2a activity, offering a novel mechanism of action. Pivotal phase 2 trial data (IMPACT-1) showed that TSND-201 produced rapid, durable symptom reductions and significantly improved response and remission rates compared with placebo.

J&J Submits sNDA to FDA for Lumateperone (CAPLYTA) to Prevent Schizophrenia Relapse

Johnson & Johnson has submitted a supplemental New Drug Application (sNDA) to the FDA seeking approval of lumateperone (CAPLYTA) for preventing schizophrenia relapse. The submission is supported by phase 3 trial results showing lumateperone 42 mg reduced relapse risk by 63% compared with placebo and significantly prolonged time to relapse.

Lumateperone, an atypical antipsychotic with high serotonin 5-HT2A and lower dopamine D2 receptor occupancy, demonstrated a favorable safety profile with no new concerns. Already approved for schizophrenia, bipolar disorder, and depression, lumateperone may expand its role in long-term schizophrenia management by providing effective relapse prevention and improved patient stability.

FDA Releases CRL Detailing Safety Concerns for MDMA-Assisted Therapy in PTSD

The FDA has released its Complete Response Letter (CRL) on MDMA-assisted therapy for PTSD, citing significant safety and trial design concerns. The agency pointed to unreported abuse-related adverse events, lack of evidence on treatment durability beyond 18 weeks, and selection bias due to prior MDMA use in many participants. Additional concerns included inconsistent adverse event reporting, inadequate long-term follow-up, and limited patient diversity. The FDA advised new randomized trials with stricter safety protocols, comprehensive data collection, and clearer assessment of psychotherapy’s contribution to outcomes before MDMA can be considered for approval.

Q3 Phase 2 Data in Psychiatry

Single Dose of MM120 (LSD) Shows Lasting Anxiety Reduction in GAD: Phase 2b Results

A phase 2b trial found that a single 100 μg dose of MM120 (lysergide D-tartrate, LSD) significantly reduced symptoms in adults with generalized anxiety disorder (GAD), with benefits lasting up to 12 weeks. The study demonstrated a clear dose-response relationship, with 100 μg emerging as the optimal dose. Patients experienced rapid, robust, and durable improvements in anxiety.

Related: Single Dose of MM120 Shows Rapid Anxiety Reduction in GAD, With Maurizio Fava, MD

Daily Ammoxetine at 40, 60 mg Outperforms Placebo for MDD in Phase 2 Trial

A phase 2 randomized clinical trial found that daily ammoxetine at 40 mg and 60 mg significantly improved Montgomery-Åsberg Depression Rating Scale (MADRS) scores compared with placebo in patients with major depressive disorder (MDD). Both doses demonstrated efficacy, safety, and tolerability, with fewer discontinuations than typically seen with other antidepressants. Notably, no patients discontinued due to sexual dysfunction or liver issues.

RE104 Reduces Postpartum Depression Symptoms by Day 7 in Phase 2 RECONNECT

The phase 2 RECONNECT trial showed that RE104, a single-dose psychedelic therapy, significantly reduced postpartum depression (PPD) symptoms by day 7, with benefits sustained through day 28. Patients receiving RE104 (30 mg) achieved a 23.0-point reduction in MADRS scores, compared with 17.2 points in the control arm.

Psychiatry Expert Perspectives You May Have Missed

Gaps in Postpartum Depression Diagnosis, With Deb York, PMHNP-BC

Strategies for Managing Tardive Dyskinesia, With Alejandro Alva, MD

How Family History Distinguishes Bipolar Depression From MDD, With Gerald Maguire, MD

When to Use Cobenfy Over Clozapine, With Chelsie Monroe, APN

What’s New in Tardive Dyskinesia, With Jonathan Meyer, MD