A preliminary, unblinded study has shown that people who took the antidepressant Prozac after suffering a traumatic injury reported fewer PTSD symptoms and lower levels of pain in the year after their injury.
With roughly half of traumatic injury patients facing some mental health decline after their injuries, the study suggests that preventative medical interventions could reduce the formation of post-traumatic stress disorder symptoms. However, larger studies would be needed to replicate these results.
“We want to actually try and prevent or mitigate the symptoms before they happen, instead of reacting to their development. This is a frameshift in the thinking around pharmaceutical management of mental health,” said Jennifer Hagen , M.D., a professor of orthopedic surgery at the University of Florida who led the new study. “The ultimate goal of this line of work is to empower our trauma teams with a tool to protect their patients’ mental health.”
The study was published July 13 in the Journal of Orthopaedic Trauma.
The team previously studied the effectiveness of post-injury resiliency training in mitigating depressive or post-traumatic stress symptoms but found little measurable effect. So in collaboration with the leaders of UF’s Department of Psychiatry, they decided to try fluoxetine. Better known as Prozac, fluoxetine is already approved to help treat the symptoms of PTSD.
The trauma team asked: Could the medicine help reduce the likelihood or severity of post-traumatic stress symptoms?
The study enrolled 68 participants in the trial who had come into the UF Health Shands Level I Trauma Center for serious injuries such as broken limbs or pelvic fractures. With some people leaving the study, a total of 35 were followed for 6 months, and 29 contributed to the final data collection a year later.
The participants were randomly assigned to take fluoxetine or calcium for 9 months and followed for an additional 3 months. Although the study was randomized, it was unblinded: Both study participants and researchers knew who was assigned to which medication group.
Patients taking fluoxetine showed a statistically significant decline in post-traumatic stress symptoms over the year, while symptoms in the calcium comparison group remained roughly unchanged.
The researchers noted that enrolling people in trials with antidepressants can be challenging, because people may be reluctant to be associated with certain medication or diagnoses.
“One of the biggest hurdles that we deal with in our studies is that mental health is very stigmatized in society,” said Diana Rijo, a research assistant and co-author of the study. Importantly, the study leaders did not attempt to diagnose patients with anxiety or depression, instead focusing on the potential for relief from post-traumatic stress symptoms.
With these promising early results in hand, the researchers have begun enrolling patients in a placebo-controlled, double-blind study to further test the effects of fluoxetine. This gold-standard study design should provide more definitive evidence about the effectiveness of antidepressants in mitigating PTSD symptoms after a traumatic injury.
Journal of Orthopaedic Trauma
Randomized controlled/clinical trial
People
Nine Months of Fluoxetine Aids in the Reduction of Posttraumatic Stress Symptoms following a Traumatic Musculoskeletal Injury: A Randomized Controlled Trial
13-Jul-2026