Q1 2025 Recap: Psychiatry

At the start of this week, HCPLive sat down with Steve Levine, MD, from Compass Pathways, to recap Q1 psychiatry highlights and preview Q2. Although the psychiatry pipeline may be “dry,” as Levine put it, Q1 had 5 regulatory updates from the US Food and Drug Administration (FDA) and 3 trials showcasing topline results for phase 2 and 3 trials in opioid use disorder (OUD), bipolar disorder, treatment-resistant depression, PTSD, ADHD, and schizophrenia.

This recap covers regulatory updates, trial announcements, and expert insights.

Q1 2025 Regulatory Updates in Psychiatry

PharmaTher Receives New Early June FDA Goal Date for Ketamine

PharmaTher received a new FDA goal date of June 4, 2025, for ketamine approval, addressing anesthesia, sedation, pain, mental health, and neurological indications. The update follows an Amendment Acknowledgment Letter after a complete response letter in 2024. PharmaTher aims to resolve the ongoing ketamine shortage.

FDA Approves Expanded Use of Buprenorphine Extended-Release Injection for OUD Treatment

The FDA approved expanded use of buprenorphine extended-release injection (SUBLOCADE) for OUD, adding new injection sites and reducing induction time from seven days to one dose with a one-hour observation period. These updates aim to improve patient adherence and flexibility while maintaining efficacy and safety in treatment.

FDA Accepts sNDA for Risperidone Extended-Release Injectable Suspension for Bipolar I Disorder

The FDA accepted the sNDA for UZEDY, an extended-release risperidone injection, for bipolar I disorder in adults. Already approved for schizophrenia in 2023, UZEDY uses copolymer technology for sustained drug release. Teva and Medincell highlight its potential to address nonadherence, a key challenge in bipolar I disorder treatment.

FDA Approves Esketamine as First Monotherapy for Treatment-Resistant Depression

The FDA approved esketamine (SPRAVATO) nasal spray as the first monotherapy for treatment-resistant depression, offering rapid symptom improvement. A phase 4 study showed superior efficacy over placebo in reducing MADRS scores at 4 weeks. Esketamine provides an alternative for patients unresponsive to oral antidepressants, with effects seen within 24 hours.

Related: Gregory Mattingly, MD: What FDA’s Approval of Esketamine as Monotherapy Means for Treatment-Resistant Depression

FDA Approves Label Update for Viloxazine Capsules to Include New Lactation Data

The FDA approved a label update for viloxazine (Quelbree) extended-release capsules, adding lactation data showing low transfer into breastmilk. The update also details its serotonin 5-HT2C receptor activity and norepinephrine transporter inhibition. Viloxazine is used for ADHD treatment and may cause adberse events of increased blood pressure and manic episodes.

Q1 2025 Trial Announcements in Psychiatry

Positive Findings

Methylone Shows Rapid PTSD Symptom Improvement in Phase 2 IMPACT-1 Trial

TSND-201 (methylone) showed significant PTSD symptom improvement in the phase 2 IMPACT-1 trial, meeting its primary endpoint with notable CAPS-5 score reductions by day 64. Rapid effects were seen by day 10. The treatment also improved secondary endpoints and demonstrated a favorable safety profile, with manageable adverse events.

Solriamfetol Significantly Reduces ADHD Symptoms in Axsome’s Phase 3 Trial

Axsome’s Phase 3 FOCUS trial found solriamfetol significantly reduced ADHD symptoms in adults, with a 45% mean reduction in AISRS scores. Improvements were seen as early as week 1, with a favorable safety profile. The treatment also reduced disease severity, supporting its potential as a new ADHD therapy.

LB-102 Shows Promise in Reducing Acute Schizophrenia Symptoms: New Phase 2 Data

LB-102, a once-daily benzamide antipsychotic, significantly reduced schizophrenia symptoms in the Phase 2 NOVA trial. Patients on LB-102 showed meaningful PANSS score reductions with a favorable safety profile. The drug was well-tolerated with minimal side effects. LB Pharmaceuticals plans to advance to Phase 3 trials in late 2025 or early 2026.

Related: Phase 2 LB-102 Data, Advancing Treatment Landscape in Schizophrenia, with John Kane, MD

Failures

SPN-820 Fails Phase 2b Trial for Treatment-Resistant Depression

SPN-820 failed to improve MADRS scores in a phase 2b trial for treatment-resistant depression. Despite a favorable safety profile, no significant benefits emerged.

Iclepertin Fails to Improve Cognition in Schizophrenia Phase 3 Study

Iclepertin failed to improve cognition in schizophrenia, missing all endpoints in a phase 3 trial. Boehringer Ingelheim discontinued further studies but remains committed to mental health therapies.

Phase 3 KOASTAL-1 Trial Fails to Show Navacaprant Significantly Improves MDD

Navacaprant failed to significantly improve depression in Phase 3 KOASTAL-1 trial. Females responded better than males. Neumora continues further investigations.

Q1 2025 Expert Perspectives in Psychiatry

Q1 and Q2 Psychiatry Updates, with Steve Levine, MD

​HCPLive interviewed Steve Levine, MD, about recent psychiatry developments in Q1, including esketamine's approval and brexpiprazole's potential for PTSD.