Frequently Asked Questions

In this review of 166 completed US antidepressant trials registered on ClinicalTrials.gov between 1993 and 2025, sex was reported in 90.36% of trials, race in 39.16%, and ethnicity in 33.13%. The authors identified incomplete demographic reporting itself as an important finding because it limits interpretation of how well trial results apply across patient groups.

Asian, American Indian or Alaska Native (AIAN), multiracial, and Hispanic or Latino participants were significantly underrepresented relative to state-level census benchmarks in the regions where trials were conducted. Reported proportions were 4.13% vs 5.67% for Asian participants (P<.001), 0.44% vs 0.89% for AIAN participants (P<.001), 1.90% vs 2.26% for multiracial participants (P=.031), and 12.42% vs 17.20% for Hispanic or Latino participants (P<.001).

In this analysis, Black and White participants did not differ significantly from the state-level census benchmarks overall. White participants made up 73.10% of trial participants versus 77.52% in the benchmark population (P=.443), and Black participants made up 20.21% versus 13.51% (P=.106).

The answer depended on the benchmark used. Female participants were overrepresented relative to state-level census data, comprising 58.27% of trial participants versus 51.06% of the underlying population (P<.001), but they were underrepresented relative to the national antidepressant-user distribution, where 67.30% of users were female (P<.001). Correspondingly, male participants were overrepresented relative to antidepressant users, at 41.73% in trials versus 32.70% in the treatment-use benchmark (P<.001).

It matters because the article states that sex, race, and ethnicity may affect antidepressant metabolism, treatment response, tolerability, adherence, and adverse effect burden, so limited diversity can reduce the generalizability of trial findings. The authors note prior evidence of sex-related pharmacokinetic differences and cite possible pharmacogenomic variation involving CYP2D6 and CYP2C19 across populations, while also emphasizing that the clinical significance of some of these differences remains uncertain.

This was a comprehensive review of completed US interventional antidepressant trials registered on ClinicalTrials.gov in adults and older adults between January 1, 1993, and September 1, 2025. Trials had to report results and include at least 1 demographic variable; after applying inclusion and exclusion criteria, 166 trials were analyzed. Representation was compared with state-level census data for the states where trials were conducted, and sex was also compared with the national distribution of antidepressant users in the United States.

The authors used state-level census data because clinical trial recruitment is typically localized, and state benchmarks better reflect the populations from which participants were actually recruited. They state that this approach was chosen to capture regional demographic variability and improve ecological validity compared with national aggregates.

The analysis was limited to ClinicalTrials.gov and therefore did not capture all clinical research, including some observational studies, some phase 1 trials, and trials not required to be registered. It also did not assess other dimensions of diversity such as sexual and gender minorities, and incomplete reporting of race and ethnicity restricted the available data. In addition, the antidepressant-use prevalence estimates used for sex comparisons may have limited generalizability because one referenced cohort was mostly White, non-Hispanic, and highly educated, although the authors note that other studies showed similar sex distributions.

The article suggests targeted outreach, culturally competent communication, transparent trial recruitment, family-inclusive approaches, and supportive services such as transportation and caregiving assistance. It also highlights multilingual resources, staff training in cultural competency, flexible visit schedules, mobile health technologies, reimbursement of travel costs, and broader eligibility criteria with fewer unnecessary exclusions as practical ways to improve recruitment and retention of underrepresented groups.