Optimizing PTSD Treatment: The Role of Brexpiprazole and Sertraline in Future Guidelines

Lori Davis, MD, clinical professor of psychiatry in the Department of Psychiatry and Behavioral Neurobiology at the University of Alabama School of Medicine, recently led a phase 3 clinical trial assessing the safety and efficacy of brexpiprazole in combination with sertraline for the treatment of posttraumatic stress disorder (PTSD). Davis and colleagues found that the combination therapy resulted in statistically significantly greater improvement of PTSD symptoms compared to treatment with sertraline plus placebo. In the video above, Davis discusses the potential impact brexpiprazole in combination with sertraline may have on future treatment guidelines, and the broader implications for patient care. She also explores the next phase of research, including large-scale effectiveness trials and integration with trauma-focused psychotherapies.

The following transcript has been edited lightly for clarity and style.

Patient Care Online: Given the lack of established second-line pharmacotherapies for posttraumatic stress disorder (PTSD), how might the combination of brexpiprazole and sertraline fit into future treatment guidelines?

Lori Davis, MD: These results will undoubtedly influence treatment guidelines. This combination demonstrated significantly better outcomes than monotherapy alone, so its place in treatment recommendations will depend on expert committees assessing the weight of the evidence.

This was a large study, and a smaller previous study also found the combination more effective than monotherapy. It remains to be seen whether guidelines will suggest it as a first-line rather than second-line option. However, as a clinician, I prioritize the individual patient in front of me over strict treatment tiers. These data suggest that starting with the combination may be more effective than monotherapy alone, offering a broader and more synergistic pharmacological approach.

While the study wasn’t specifically designed to address this, the pharmacology supports the idea that using both medications together provides greater benefits than either alone. For a patient with severe symptoms and significant impairment in relationships and occupational functioning, I would lean toward the best available evidence—these data should certainly be considered in treatment decisions.

Patient Care: What are the next steps in your research regarding brexpiprazole and sertraline?

Dr Davis: After phase 3 studies, the next steps could include large-scale effectiveness trials to evaluate real-world implementation. Future research might compare this combination with established psychotherapies or explore how it performs when combined with trauma-focused psychotherapies. A landmark study comparing the combination treatment alone, psychotherapy alone, and their integration would be particularly valuable.

I want to encourage providers—treating PTSD is challenging because patient presentations vary widely. The suffering extends beyond individuals to families, workplaces, and society. These new findings offer hope, not just for symptom relief but also for improving quality of life, relationships, and overall functioning.

Lori Davis, MD, is an adjunct professor of psychiatry at the University of Alabama at Birmingham Heersink School of Medicine. Dr Davis also serves as associate chief of staff for research and development service for the VA Medical Center in Tuscaloosa, Alabama.