What is the new drug for PTSD? Understanding Recent Developments

October 7, 2025 •

4 min read

For over two decades, the U.S. Food and Drug Administration (FDA) has not approved a new drug specifically for post-traumatic stress disorder (PTSD), highlighting a significant unmet need for more effective treatments. A promising combination drug therapy was recently considered, but ultimately denied, leading to intense focus on other investigational options, including psychedelic-assisted therapies, in the search for what is the new drug for PTSD.

Quick Summary

This article explores recent developments in PTSD pharmacotherapy, detailing the FDA's rejection of brexpiprazole in combination with sertraline, the status of MDMA-assisted therapy, and the progress of other investigational compounds like ibogaine and methylone.

Key Points

FDA Rejection of Brexpiprazole: In 2025, the FDA rejected the combination of brexpiprazole and sertraline for PTSD, citing insufficient data from clinical trials.
MDMA Not Approved for PTSD: Following trial inconsistencies and data concerns, the FDA declined to approve MDMA-assisted therapy for PTSD in 2024, but further research is ongoing.
Ibogaine Shows Early Promise: A Stanford study found that the psychedelic ibogaine significantly reduced PTSD symptoms in veterans, leading to state-funded trials in Texas.
Active and Diverse Drug Pipeline: Numerous novel compounds, including BNC210, BI 1358894, and CORT108297, are in clinical trials targeting various neurobiological pathways.
Current Options Are Limited: For over 20 years, no new drug has been FDA-approved for PTSD, leaving standard SSRIs as the only approved pharmacological option, which is not effective for many patients.
Cannabinoids for Specific Symptoms: Synthetic cannabinoids like dronabinol are being investigated specifically for treating PTSD-related nightmares, a common symptom.
Combination Therapies Under Study: The failure of brexpiprazole has not halted the exploration of combination approaches, with researchers still testing different drug pairings.

A Decades-Long Stagnation in PTSD Drug Development

For many patients suffering from post-traumatic stress disorder (PTSD), the available pharmacological treatments offer only partial relief. For years, the standard of care has primarily involved selective serotonin reuptake inhibitors (SSRIs) like sertraline and paroxetine, both approved over two decades ago. These medications are often insufficient, and many patients experience side effects or lack of efficacy. This lack of progress underscores the need for new treatments that can provide more comprehensive and lasting relief from PTSD's complex symptoms.

The Rise and Fall of Brexpiprazole as a New Option

In early 2025, there was anticipation for the potential approval of brexpiprazole (Rexulti) combined with sertraline for adult PTSD, potentially the first new FDA-approved drug in over 20 years. Brexpiprazole, an atypical antipsychotic, modulates neurotransmitter systems, aiming to address PTSD symptoms differently than SSRIs alone. One Phase 3 trial showed the combination significantly improved PTSD symptom scores compared to sertraline plus a placebo.

Why the FDA Rejected Brexpiprazole

Despite positive results in one trial, the FDA rejected the application in September 2025, citing insufficient evidence of effectiveness due to inconsistent results across the three submitted clinical trials. This decision was a setback for the involved companies, Otsuka and Lundbeck, and disappointed many hoping for a new PTSD treatment.

Psychedelic-Assisted Therapies: An Evolving Frontier

Research into psychedelic-assisted therapies, which use psychoactive substances alongside psychotherapy, is a prominent area in PTSD treatment. Recent FDA decisions highlight both their promise and regulatory challenges.

MDMA-Assisted Therapy

Clinical trials for MDMA-assisted therapy for PTSD showed encouraging results, with many participants no longer meeting the diagnostic criteria after treatment. MDMA is believed to aid therapy by fostering connectedness and empathy, helping patients process trauma. However, in 2024, the FDA's advisory committee and the agency itself declined approval due to concerns about potential bias from unblinding, allegations of therapist misconduct, and data reliability issues. Research continues with cautious optimism.

Ibogaine and Other Psychedelics

Ibogaine, a plant-based psychedelic, is also being studied. A 2024 Stanford Medicine study found that ibogaine treatment improved symptoms of depression, anxiety, and PTSD in veterans with traumatic brain injuries (TBI). Improvements in brain activity related to neuroplasticity and the fear response were observed. Texas is funding ibogaine trials for veterans and first responders, though it remains a federally controlled substance. Other related compounds, such as methylone, are also in early trials.

A Diverse and Active Pipeline

The rejections of brexpiprazole and regulatory caution around psychedelics emphasize the need for varied therapeutic approaches. The PTSD drug pipeline is currently active and diverse.

Investigational Compounds

BNC210: An oral drug in Phase 2b trials for reducing PTSD symptom severity.
BI 1358894: A novel PDE9A inhibitor in clinical trials for PTSD.
Balovaptan: A vasopressin 1a receptor antagonist being evaluated for PTSD.
CORT108297: A selective glucocorticoid receptor antagonist being tested in veterans with PTSD.
Dronabinol and Nabilone: Synthetic cannabinoids explored for treating PTSD-related nightmares.

Comparison of New and Investigational PTSD Therapies


Therapy/Drug	Mechanism of Action	Clinical Status	Key Findings
Brexpiprazole + Sertraline	Modulates serotonin and dopamine systems; augments standard SSRI therapy.	Rejected by FDA in 2025 due to inconsistent trial results.	Showed statistically significant improvement over placebo in one Phase 3 trial.
MDMA-Assisted Therapy	Promotes self-reflection and connectedness via serotonin release; used with psychotherapy.	FDA declined approval in 2024, citing study concerns. Research continues.	Significant symptom reduction in clinical trials; high percentage of patients no longer met PTSD criteria.
Ibogaine	Plant-based psychoactive compound; affects brain activity related to fear response and neuroplasticity.	Currently in clinical trials for veterans in Texas, but a Schedule I drug federally.	Demonstrated significant improvements in PTSD, anxiety, and TBI symptoms in veterans.
BNC210	Negative allosteric modulator of α7 nicotinic acetylcholine receptors.	Phase 2b trial assessing efficacy in reducing PTSD symptoms.	Potentially represents a new therapeutic class for PTSD.
CORT108297	Blocks cortisol via selective glucocorticoid receptor antagonism.	Clinical trials underway specifically for veterans with PTSD.	Focuses on addressing neuroendocrine dysregulation seen in PTSD.

Conclusion

The search for an effective new drug for PTSD continues. The FDA's recent rejection of brexpiprazole combined with sertraline highlights the strict requirements for regulatory approval. Psychedelic-assisted therapies, though facing their own challenges, offer new research avenues. The current drug pipeline, with compounds targeting various neurobiological mechanisms, shows a shift towards more comprehensive treatment approaches. While there is no single approved "new drug for PTSD," ongoing research provides hope for better treatments in the future.

What is the new drug for PTSD? Exploring therapeutic options

Brexpiprazole Combination Rejected: The FDA declined to approve brexpipazole with sertraline in 2025, citing insufficient evidence of effectiveness despite positive findings in one of three submitted trials.
MDMA-Assisted Therapy on Hold: After a setback with the FDA due to study design concerns, MDMA-assisted therapy is not approved for PTSD, but research continues with updated protocols.
Ibogaine Trials for Veterans: Early, promising studies in veterans with TBI and PTSD have led to state-funded clinical trials for ibogaine, though it remains a federally restricted substance.
Diverse Pipeline of Novel Drugs: The drug pipeline includes many new compounds, such as BNC210, BI 1358894, and CORT108297, which target alternative neurobiological pathways.
Traditional Medications Still Standard: The current FDA-approved medications for PTSD remain SSRIs (sertraline and paroxetine), which are often insufficient for many patients.
Focus on Nightmares and Sleep: Several new treatments, including specific cannabinoids like dronabinol and repurposed drugs like doxazosin, are specifically being tested for PTSD-associated nightmares.
Off-Label Usage Continues: Many medications are used off-label for PTSD, but this practice carries risks due to a lack of robust evidence for this specific indication.
Importance of Psychotherapy: Alongside pharmacological research, therapies like Cognitive Behavioral Therapy (CBT) and Eye Movement Desensitization and Reprocessing (EMDR) remain crucial and are often combined with medication.

Frequently Asked Questions

No, a supplemental new drug application for brexpiprazole in combination with sertraline was rejected by the FDA in September 2025 due to insufficient evidence of effectiveness.

The FDA declined to approve MDMA-assisted therapy for PTSD in 2024 due to concerns about data reliability, functional unblinding in trials, potential bias, and reports of misconduct.

Ibogaine is a plant-based psychedelic that has shown promising results in initial studies for treating PTSD and TBI in veterans. It is currently in further clinical trials and funded by some state initiatives, but it is not an FDA-approved treatment.

The only FDA-approved medications for PTSD are the SSRIs sertraline (Zoloft) and paroxetine (Paxil).

Yes, other investigational drugs include BNC210, a modulator of nicotinic acetylcholine receptors, and CORT108297, a cortisol blocker, among others targeting different biological pathways.

Despite significant interest and promising research, psychedelic-assisted therapies like MDMA and ibogaine still face complex regulatory hurdles and require more rigorous safety and efficacy data before federal approval.

While ketamine is sometimes used off-label for comorbid depression, recent clinical trials for treating PTSD have not demonstrated a clear benefit, and its use is not officially recommended for PTSD itself.

Research is ongoing for treatments specifically for nightmares, including studies on synthetic cannabinoids like dronabinol and repurposed medications like doxazosin, though definitive results are still pending.