Starting an SSRI in the hospital eases PTSD symptoms and pain a year later
STUDY: Pazik M et al, Journal of Orthopaedic Trauma 2026
STUDY TYPE: Randomized controlled trial
FUNDING: University of Florida Orthopaedic Trauma Research Foundation
Background
Up to half of patients who survive major fractures develop lasting psychological distress. Fluoxetine is effective for active PTSD, but whether it prevents PTSD is unknown. Earlier attempts to prevent PTSD with escitalpram failed, and this is the first trial to test fluoxetine.
The Study
- 68 adults hospitalized for high-energy fractures or pelvic trauma requiring surgery.
- Randomized to fluoxetine (10mg, titrated to 20mg) or a calcium placebo, started in the hospital (right after surgery) and continued for nine months.
- Unblinded; both patients and clinicians knew the assignment.
- PTSD symptoms (PSS-SR), pain (PEG), sleep (PSQI), depression (BDI-II), and anxiety (BAI) were tracked out to one year.
Results
Although the patients had elevated PTSD symptoms at the start of the study, they would not qualify for a diagnosis of PTSD because it was within a few days of the trauma (PTSD is diagnosed a month later).
PTSD symptoms fell steadily in the fluoxetine group over the year while the placebo group showed little change. Pain scores improved with fluoxetine but not placebo, and the fluoxetine group also reported a better ability to participate in social activities. Sleep quality worsened in the placebo group over the first three months while staying stable with fluoxetine.
Depression, anxiety, and social isolation scores didn’t differ between groups. When the medication was stopped at nine months, PTSD symptoms didn’t rebound over the following three months.
Side Effects
Lightheadedness, nausea, and palpitations were the most common complaints attributed to fluoxetine, but overall side effects were similar to placebo. No manic-like activation and no suicidality on fluoxetine.
Limitations
Small pilot sample, single center, no blinding, did not measure DSM diagnoses. A third of patients randomized to fluoxetine dropped out before ever taking it.
Practice Implications
- These are pilot data, not practice-changing on their own, but open the door to further research.
- It’s not clear why escitalopram failed in small, earlier trials of PTSD-prevention (in 2012 and 2015), but that discrepancy raises doubts about the validity of this trial, particularly with the lack of blinding.
- When you see a patient after a trauma, therapy is first line. Learn which strategies work, which can make it worse (hint: debriefing), and which medication has decent evidence to prevent PTSD (hint: hydrocortisone) in our Carlat Podcast.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
