Decades After the NIH Revitalization Act: Persistent Gaps in Diversity of US Antidepressant Trials

Background: Clinical trials for antidepressants inform prescribing practices and clinical guidelines, but the demographic composition of the trial participants affects the generalizability. For this reason, the sex, race, and ethnicity reporting and participant composition in US antidepressant trials must be investigated.

Methods: We searched ClinicalTrials.gov for completed US antidepressant trials conducted between January 1, 1993, and September 1, 2025. Data on trial characteristics and the reporting of sex, race, and ethnicity were extracted (n=166 trials). Normality of the observed trial-level sex distributions was assessed using the Shapiro-Wilk test. Paired t tests or Wilcoxon signed-rank tests were conducted to assess representation adequacy compared to annual state census data.

Results: Sex was reported by 90.36% of trials, race by 39.16%, and ethnicity by 33.13%. Across trials reporting race or ethnicity, pooled participant proportions showed underrepresentation of Asian (4.13% vs 5.67% census, P<.001), American Indian/Alaska Native (AIAN, 0.44% vs 0.89%, P<.001), multiracial (1.90% vs 2.26%, P=.031), and Hispanic/Latino participants (12.42% vs 17.20%, P<.001). Across trials, female participants accounted for 58.27% of participants, which was significantly higher than the state-level benchmark but significantly lower than the benchmark female proportion among antidepressant users (P<.001).

Conclusions: Reporting gaps persist and multiple minority racial/ethnic groups remain underrepresented in US antidepressant trials, limiting generalizability. Clearer reporting standards and targeted recruitment strategies are needed.