It has been 24 years since a pharmaceutical was last approved for posttraumatic stress disorder (PTSD). The condition is notoriously difficult to treat, with up to 40% patients finding no relief from symptoms through psychotherapy or current medications.
Many clinicians, advocates, and patients had pinned their hopes on the psychedelic drug midomafetamine with assisted therapy (MDMA-AT). However, in August, the US Food and Drug Administration (FDA) rejected it. At this point, it’s unclear when the therapy will be available, if ever.
“Not getting the FDA approval of any drug at this point is a setback for the field,” Lori Davis, MD, a senior research psychiatrist at the Birmingham Veterans Affairs (VA) Health Care System in Birmingham, Alabama, told Medscape Medical News.
Having an FDA-approved product would have helped increase public awareness of PTSD and driven interest in developing new therapies, said Davis, who is also adjunct professor of psychiatry at the Heersink School of Medicine, University of Alabama at Birmingham.
A Treatable Condition
So with MDMA-AT off the table, where does the field go next?
A public meeting in September hosted by the Reagan-Udall Foundation for the FDA in sought to answer that question. Agency officials joined representatives from the Department of Defense (DoD) and VA, patients, advocates, and industry representatives to discuss the current treatment landscape and what can be done to accelerate development of PTSD treatment.
Despite the common belief that PTSD is intractable, it “is a treatable condition,” Paula P. Schnurr, PhD, executive director of the VA National Center for PTSD, said at the meeting.
“There are effective treatments that work well for a lot of people, although not everyone has a satisfactory response,” she added.
The most effective psychotherapies are “trauma-focused,” and include cognitive processing therapy, eye movement desensitization and reprocessing, and prolonged exposure, according to the VA National Center for PTSD.
Three drugs have been approved by the FDA for PTSD: Venlafaxine (Effexor) in 1993, sertraline (Zoloft) in 1999, and paroxetine (Paxil) in 2000.
However, as the September meeting demonstrated, more therapies are needed.
“It’s clear to FDA and the federal government at large that there is an unmet need for safe and effective therapies to treat PTSD,” Bernard Fischer, MD, deputy director of the Division of Psychiatry in the Office of New Drugs at FDA’s Center for Drug Evaluation and Research, said at the meeting.
There is no shortage of research, Fischer added. Nearly 500 trials focused on PTSD are listed on clinicaltrials.gov are recruiting participants now or plan to soon.
Unsurprisingly, one of the primary drivers of PTSD therapeutics research is the VA. About 14% of the 5.7 million veterans who received care through the VA in 2023 had a diagnosis of PTSD.
“The US military is currently losing thousands of service members each year to PTSD- related disability discharges,” US Army Maj. Aaron Wolfgang, MD, a psychiatrist at the Walter Reed National Military Medical Center, said at the meeting. Only about 12%-20% of patients achieve remission with conventional therapies, added Wolfgang, who also is an assistant professor at the Uniformed Services University.
“For these reasons, establishing better treatments for PTSD is not only a matter of humanitarianism but also a pressing matter of national security,” he said.
The VA has committed at least $230 million to more than 140 active research projects in PTSD, Miriam J. Smyth, PhD, acting director of the clinical science, research and development service at the VA, said at the Reagan-Udall meeting.
One of the VA projects is the PTSD psychopharmacology initiative, which began in 2017 and now has 14 active clinical trials, said Smyth, who is also acting director for brain behavior and mental health at the VA. The first study should be finished by 2025.
The Million Veteran Program, with more than 1 million enrollees, has led to the discovery of genes related to re-experiencing traumatic memories and has confirmed that both PTSD and traumatic brain injury are risk factors for dementia, Smyth said.
The DoD has created a novel platform that establishes a common infrastructure for testing multiple drugs, called M-PACT. The platform allows sharing of placebo data across treatment arms. Drugs cycle off the platform if evidence indicates probability of success or failure.
Four trials are actively recruiting veterans and current service members. One is looking at vilazodone, approved in 2011 for major depressive disorder. It is being compared with placebo and fluoxetine in a trial that is currently recruiting.
Another trial will study daridorexant (sold as Quviviq), an orexin receptor antagonist, against placebo. The FDA approved daridorexant in 2022 as an insomnia treatment. A core issue in PTSD is sleep disruption, noted Davis.