Clinical Summary
Clinical Summary: Decades After the NIH Revitalization Act: Persistent Gaps in Diversity of US Antidepressant Trials
Psychiatrists routinely apply antidepressant trial data to patients whose sex, race, and ethnicity can affect treatment response, tolerability, and adherence. This analysis shows that even decades after federal efforts to improve inclusion, many US antidepressant trials still do not adequately report or reflect the populations seen in practice.
Design
A comprehensive review was conducted on completed clinical trials in the United States that had been registered on the ClinicalTrials.gov website in adults and older adults between January 1, 1993, and September 1, 2025.
N
166 clinical trials
Population
completed clinical trials in the United States that had been registered on the ClinicalTrials.gov website in adults and older adults
Duration
between January 1, 1993, and September 1, 2025
Key Findings
- Among 166 clinical trials, sex reporting was available in 90.36% of clinical trials, while race and ethnicity were reported in 39.16% and 33.13% of trials, respectively.
- Participants identifying as Hispanic or Latino were significantly underrepresented relative to state-level census benchmarks (12.42% vs 17.20%, P <.001).
- Asian (4.13% vs 5.67%, P<.001), AIAN (0.44% vs 0.89%, P<.001), and multiracial participants (1.90% vs 2.26%, P=.031) were all significantly underrepresented compared to annual state census data.
- Female participants were significantly overrepresented relative to the state-level benchmark, constituting 58.27% of trial participants compared to 51.06% of the population (P <.001).
- When compared with the national distribution of antidepressant users, female participants remained significantly underrepresented in antidepressant clinical trials (58.27% vs 67.30%, P <.001), while male participants were significantly overrepresented (41.73% vs 32.70%, P<.001).
Clinical Bottom Line
US antidepressant trials still have major gaps in demographic reporting and underenroll several racial and ethnic groups, while also failing to match the sex distribution of actual antidepressant users. Clinicians should be cautious about assuming antidepressant efficacy and tolerability data generalize evenly across diverse patients.
Practice Implications
- When applying antidepressant trial data, pay closer attention to who was actually enrolled and whether sex, race, and ethnicity were reported at all; in this review, race was reported in only 39.16% and ethnicity in 33.13% of trials.
- Be especially careful extrapolating antidepressant evidence to Asian, AIAN, multiracial, and Hispanic or Latino patients, who were significantly underrepresented versus state census benchmarks.
- Interpret sex-based generalizability in context: women made up 58.27% of trial participants, which exceeded the state-level population benchmark but remained below the national antidepressant-user benchmark of 67.30%.
- For future trial design and recruitment, prioritize strategies named in the article to improve inclusion and retention, including culturally competent communication, multilingual resources, flexible visit schedules, and supportive services such as transportation and caregiving assistance.
