Psychiatry Month in Review: December 2024

December had burst with holiday cheer, snow on Christmas Eve on the East Coast, and most importantly, pivotal developments in psychiatry.

The final month of 2024 brought both triumphs and challenges: brilaroxazine demonstrated sustained efficacy for schizophrenia, and brexpiprazole with sertraline showed rapid PTSD symptom relief. Conversely, navacaprant failed to meet expectations in major depressive disorder (MDD) trials. Meanwhile, Intra-Cellular Therapies have made strides with lumateperone as an MDD adjunctive therapy.

As the mental health crisis persists, December's updates and the trajectory of the psychiatry pipeline hold promise for the new year. Despite setbacks like the US Food and Drug Administration (FDA) issuing a Complete Response Letter (CRL) for MDMA-assisted therapy, innovative treatments signal hope for 2025 and beyond, as psychiatry evolves to address unmet needs and improve patient outcomes.

Phase 3 Data: The Good, The Discouraging

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

The phase 3 KOASTAL-1 trial found that navacaprant, a kappa opioid receptor antagonist, did not significantly improve symptoms of MDD compared with placebo, failing its primary endpoint. However, females on navacaprant showed greater improvement in depression and anhedonia symptoms, as measured by MADRS and SHAPS scores, respectively, compared with males. Despite the disappointing results, ongoing trials (KOASTAL-2, KOASTAL-3, KOASTAL-LT) will continue to explore navacaprant's potential in MDD treatment.

Brilaroxazine Shows Long-Term Efficacy in Schizophrenia in Phase 3 RECOVER

The Phase 3 RECOVER study's open-label extension found brilaroxazine sustained efficacy for schizophrenia beyond 1 year. Reviva Pharmaceuticals reported clinically meaningful improvements in PANSS total, positive, and negative symptom scores across doses (15 mg, 30 mg, 50 mg). Long-term safety data showed low treatment-related adverse events, mostly mild or moderate, with no serious events linked to brilaroxazine. Final data, including biomarkers, are expected in early 2025, further supporting its potential to reduce the burden of this condition.

Brexpiprazole with Sertraline Significantly Reduces PTSD Symptoms in 10 Days

A phase 3 trial revealed that brexpiprazole with sertraline significantly reduced PTSD symptoms within 10 days compared to sertraline with placebo. Participants experienced greater improvements in CAPS-5 scores by week 10 and secondary endpoints, including CGI-S and B-IPF scores, indicating enhanced psychological function and reduced illness severity. The combination showed a safety profile consistent with brexpiprazole's approved uses. These findings support brexpiprazole’s potential as a new therapeutic option for PTSD, with an FDA decision expected by February 2025.

What’s Moving in the Psychiatry Pipeline

Intra-Cellular Therapies Submits sNDA to FDA for Lumateperone as an MDD Adjunctive Therapy

Intra-Cellular Therapies submitted a supplemental New Drug Application (sNDA) to the FDA for lumateperone (CAPLYTA) as an adjunctive therapy for MDD. Two phase 3 trials demonstrated significant improvements in MDD symptoms, with lumateperone reducing MADRS scores by 4.9 and 4.5 points, respectively, compared to placebo (P < .0001). Benefits were evident as early as week 1, with further improvements in clinical severity and depressive symptoms by week 3.

Where is the Mental Health Crisis Heading in 2025? Hear from Experts

The mental health crisis, rooted in longstanding societal and healthcare disparities, has been magnified by the COVID-19 pandemic and modern stressors including 24/7 media and social isolation. Experts emphasize that this is not a sudden crisis, but an ongoing issue spotlighted by increased awareness and reporting. In 2025, challenges are expected to persist, with access to care and high medication costs hindering progress. Promising therapies, including psychedelics and new medications, are in development, but gaps in affordability and stigma remain. Experts advocate for early intervention, mental health education, and integrating care at the primary level to address this multifaceted crisis effectively.

MDMA-Assisted Therapy for PTSD: From Excitement to Disappointment

The Rise, Fall (and Future?) of MDMA-Assisted Therapy

MDMA-assisted therapy for PTSD has experienced a tumultuous journey in 2024, transitioning from hope to disillusionment. Despite promising phase 3 trials showing its potential to improve PTSD symptoms, the FDA rejected its approval due to safety concerns and functional unblinding issues.

This decision marked a significant setback in the integration of psychedelics into mainstream mental health treatment, although experts remain optimistic about the future of psychedelic-assisted therapies. Ongoing research into other psychedelics, such as psilocybin, suggests potential advancements. While challenges persist, the landscape for innovative psychiatric treatments continues to evolve.

The Top Psychiatry News in 2024

Psychiatry Year in Review: 2024

The 2024 Psychiatry Year in Review highlights pivotal developments in mental health care last year. Key milestones include the FDA’s approval of xanomeline and trospium chloride (Cobenfy), a novel schizophrenia treatment, and over-the-counter naloxone for opioid overdose. While MDMA-assisted therapy for PTSD faced a setback with a CRL, optimism persists for its future. Breakthroughs in psychedelic-assisted therapies, such as MM120 for anxiety, and new CPT codes signal a shift in psychiatric care.

Advances in treatments for bipolar disorder, schizophrenia, and depression, alongside long-term safety data on olanzapine-samidorphan, underscore the evolving landscape of psychiatric innovation and patient care.