Rexulti in Combination With Sertraline for PTSD: Upcoming FDA Advisory Committee Discussion

Dzmitry/AdobeStock

On Friday July 18, 2025, the US Food and Drug Administration (FDA) advisory committee will discuss the supplemental New Drug Application (sNDA) for brexpiprazole (Rexulti) tablets, submitted by Otsuka Pharmaceutical Company, for the treatment of adults with posttraumatic stress disorder (PTSD), in combination with sertraline.¹

With no new treatments for PTSD in nearly 25 years and approximately 13 million Americans struggling with the disorder,² this news offers a beacon of hope after the disappointing outcome for midomafetamine (MDMA)-assisted psychotherapy (MDMA-AT) late last year.³

In August 2024, the FDA issued a complete response letter for MDMA-AT for PTSD, requesting an additional phase 3 trial to examine safety and efficacy, rather than the approving the psychedelic.⁴ Many were saddened by this result, including federal veterans advocates at the Heroic Hearts Project. “The FDA’s decision is a missed opportunity to embrace groundbreaking science, save countless Veteran lives, and honor the sacrifices made by those who served our country. If this critical treatment remains inaccessible, we face losing an additional 6000 Veterans to suicide this year alone—and every year thereafter,” shared Heroic Hearts in a statement following the denial of MDMA-AT.⁵ The push for MDMA-AT’s approval also had bipartisan support; Over 60 members of Congress from both parties sent a letter to President Biden, his administration, and FDA officials, urging them to “follow the science” when it came to MDMA-AT.⁶

Rexulti, while new to the PTSD space, is already on the market for several other disease states. It was approved by the FDA in 2015 as an adjunctive therapy to antidepressants in adults with major depressive disorder (MDD) and as a monotherapy treatment for schizophrenia in adults, and was most recently approved in May 2023 for the treatment of agitation associated with Alzheimer disease dementia—the first FDA-approved treatment option for this indication.⁷ Although the mechanism of action of Rexulti is unknown, it has high receptor binding affinity to norepinephrine, serotonin, and dopamine receptors, and is an antagonist at norepinephrine α1B and α2C receptors and serotonin 5-HT2A receptors, as well as a partial agonist at serotonin 5-HT1A and dopamine D2 receptors.

The original Prescription Drug User Fee Act target action date for Rexulti in combination with sertraline for PTSD was planned for February 8, 2025, and has been postponed until after this week’s advisory committee discussion.

Stay tuned for more coverage on the outcome of the advisory committee meeting, right here at PsychiatricTimes.com.

References

1. July 18, 2025: Meeting of the Psychopharmacologic Drugs Advisory Committee Meeting Announcement. US Food and Drug Administration. Accessed July 15, 2025. https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-18-2025-meeting-psychopharmacologic-drugs-advisory-committee-meeting-announcement-07182025

2. How common is PTSD in adults? US Department of Veterans Affairs. Updated March 26, 2025. Accessed July 15, 2025. https://www.ptsd.va.gov/understand/common/common_adults.asp

3. Duerr HA. With MDMA on hold, what’s next for psychedelics? Psychiatric Times. September 11, 2024. https://www.psychiatrictimes.com/view/with-mdma-on-hold-whats-next-for-psychedelics

4. Lykos Therapeutics announces complete response letter for midomafetamine capsules for PTSD. August 9, 2024. Accessed July 15, 2025. https://news.lykospbc.com/2024-08-09-Lykos-Therapeutics-Announces-Complete-Response-Letter-for-Midomafetamine-Capsules-for-PTSD

5. Heroic Hearts and Healing Breakthrough response to FDA’s Denial of MDMA-AT. Heroic Hearts Project. August 9, 2024. Accessed July 15, 2025. https://heroicheartsproject.org/response-to-fdas-denial-of-mdma-at/

6. Bergman leads 60 members in letter to highlight new groundbreaking therapy, stop veteran suicide. News release. August 5, 2024. Accessed. July 15, 2025. https://bergman.house.gov/news/documentsingle.aspx?DocumentID=1303

7. Kuntz L. FDA approves first treatment for agitation associated with Alzheimer disease dementia. Psychiatric Times. May 10, 2023. https://www.psychiatrictimes.com/view/fda-approves-first-treatment-for-agitation-associated-with-alzheimer-disease-dementia