After 25 Years Without a New PTSD Drug, Here’s What’s in the Pipeline
Roughly 13 million Americans live with PTSD. The FDA has approved only two medications for it, both more than two decades old.
The FDA approved sertraline, brand name Zoloft, to treat post-traumatic stress disorder in 1999, followed by paroxetine, brand name Paxil, in 2001. Since then, a quarter century has passed, and no other medication has cleared the FDA’s bar for a PTSD indication.
Both approved drugs are selective serotonin reuptake inhibitors (SSRIs), both were studied in trials that showed only moderate effect sizes, and both remain, today, the entire FDA-approved pharmacological toolkit for a condition the Department of Veterans Affairs estimates affects roughly 13 million Americans. SSRIs are antidepressants that affect serotonin in the brain.
“There are at least 13 million people living with PTSD and very few options. There are two approved pharmaceutical options, both SSRIs that are modestly effective at best, and there hasn’t been an approval for PTSD in 25 years. A huge unmet need,” said Steve Levine, M.D., chief patient officer for Compass Pathways. The biotechnology company is developing a synthetic psilocybin treatment and taking part in a VA-affiliated study testing it for treatment-resistant depression.
Read More: VA Is Running Multiple Psychedelic Drug Trials for Veterans — With One Shared Goal
Why the Drought Happened
Response rates to sertraline and paroxetine in clinical trials for PTSD have ranged widely, from roughly 24% to 60% depending on the study, and relatively few patients reach full remission. Physician surveys have found real dissatisfaction with both drugs as a first-line PTSD treatment, reflected in how infrequently they’re actually prescribed as a first choice compared to how often clinical guidelines recommend them. Several other antidepressants, including fluoxetine and venlafaxine, are commonly prescribed off-label for PTSD despite never receiving a formal FDA indication for it, because the approved options simply haven’t been good enough for a large share of patients.
What’s Moving Through Development Now
The most advanced psychedelic-assisted option specifically targeting PTSD is MDMA-assisted therapy, which received FDA Breakthrough Therapy Designation in 2017 after pooled trial data showed a notably large effect size compared to existing treatments. The VA launched its first-ever MDMA (Ecstasy)-assisted therapy clinical trial for veterans in 2026, testing the drug specifically in veterans with severe PTSD and co-occurring alcohol use disorder.
Read More: New VA Trial of MDMA Psychedelic for PTSD: What Veterans Need to Know
Separately, Compass Pathways, the company developing the psilocybin treatment COMP360 for treatment-resistant depression, completed an open-label Phase 2 safety study of the same drug in PTSD in 2024. That trial was small, with only 22 participants, and focused primarily on safety and feasibility rather than proving efficacy.
But the results were encouraging enough that the company has since moved into a Phase 2B/3 trial of roughly 300 participants across multiple countries.
Beyond the psychedelic-assisted therapies, at least one non-psychedelic candidate has also been tested in late-stage trials: brexpiprazole, an antipsychotic already approved for other conditions, studied as an add-on treatment for PTSD patients who hadn’t fully responded to sertraline or paroxetine alone, though that particular trial was terminated early due to enrollment challenges rather than any safety concern.
What This Means for the Timeline
None of the options currently in trials are close to being available to patients today. The VA’s MDMA trial and Compass’s PTSD program are both still gathering data, and even a successful trial result would still need to clear FDA review before reaching a pharmacy. Historically, that full process, from a pivotal trial’s start to an approved drug on the market, has taken years even under an accelerated regulatory pathway.
What’s changed is the level of institutional investment behind closing that 25-year gap. Both a federal executive order directing agencies to accelerate psychedelic treatment research and direct VA sponsorship of an MDMA trial represent a level of coordinated government interest in new PTSD pharmacology that hasn’t existed since paroxetine’s approval in 2001.
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