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

Mathews Sajan, BS; Ria R. Trivedi; Sohail R. Daulat, BS; Saren Sall; Francisco A. Moreno, MD

J Clin Psychiatry 2026;87(3):26m16436

Abstract

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.

J Clin Psychiatry 2026;87(3):26m16436

Author affiliations are listed at the end of this article.

Members Only Content

This full article is available exclusively to Professional tier members. Subscribe now to unlock the HTML version and gain unlimited access to our entire library plus all PDFs. If you're already a subscriber, please log in below to continue reading.

Subscribe Now

Already a member? Log in

References (29)

González HM, Tarraf W, Whitfield KE, et al. The epidemiology of major depression and ethnicity in the United States. J Psychiatr Res. 2010;44(15):1043–1051.
National Academies of Sciences. Engineering, and medicine; Policy and Global Affairs; Committee on women in science, engineering, and medicine; Committee on improving the representation of women and underrepresented minorities in clinical trials and researchBibbins-Domingo K, Helman A, eds. Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups. National Academies Press (US); 2022. Accessed March 26, 2026. http://www.ncbi.nlm.nih.gov/books/NBK584403/
Polo AJ, Makol BA, Castro AS, et al. Diversity in randomized clinical trials of depression: a 36-year review. Clin Psychol Rev. 2019;67:22–35. PubMed CrossRef
Zhou EW, Jackson MJ, Ledley FD. Spending on phased clinical development of approved drugs by the US national Institutes of health compared with industry. JAMA Health Forum. 2023;4(7):e231921. CrossRef
Murphy E, Hou L, Maher BS, et al. Race, genetic ancestry and response to antidepressant treatment for major depression. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2013;38(13):2598–2606.
Kornstein SG, Schatzberg AF, Thase ME, et al. Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry. 2000;157(9):1445–1452.
Turner BE, Steinberg JR, Weeks BT, et al. Race/ethnicity reporting and representation in US clinical trials: a cohort study. Lancet Reg Health Am. 2022;11. 10.1016/j.lana.2022.100252 PubMed CrossRef
Daulat SR, Dholaria N, Patil S, et al. Demographic Reporting and Representation Among Neurosurgical Clinical Trials in the United States. World Neurosurg. 2026;210:124973. CrossRef
Dholaria N, Daulat SR, Parmar R, et al. Spine Disease Clinical Trial Representation: An Analysis of Racial, Ethnic, and Gender Diversity. Neurosurgery. 2025;97(5):1062–1071. CrossRef
Bielinski SJ, St Sauver JL, Olson JE, et al. Cohort profile: the right drug, right dose, right time: using genomic data to individualize treatment protocol (RIGHT protocol). Int J Epidemiol. 2020;49(1):23–24k. CrossRef
Luo Y, Kataoka Y, Ostinelli EG, et al. National prescription patterns of antidepressants in the treatment of adults with major depression in the US between 1996 and 2015: a Population Representative Survey based analysis. Front Psychiatry. 2020;11:35. CrossRef
Panchal N, Saunders H, Rudowitz R, et al. The implications of COVID-19 for mental health and substance use. 2023. Accessed March 26, 2026. https://www.kff.org/mental-health/the-implications-of-covid-19-for-mental-health-and-substance-use/
World Health Organization. COVID-19 pandemic triggers 25% increase in prevalence of anxiety and depression worldwide. 2022. Accessed March 26, 2026. https://www.who.int/news/item/02-03-2022-covid-19-pandemic-triggers-25-increase-in-prevalence-of-anxiety-and-depression-worldwide
Kupcova I, Danisovic L, Klein M, et al. Effects of the COVID-19 pandemic on mental health, anxiety, and depression. BMC Psychol. 2023;11(1):108.
Lorenz T, Rullo J, Faubion S. Antidepressant-Induced female sexual dysfunction. Mayo Clin Proc. 2016;91(9):1280–1286.
Bigos KL, Pollock BG, Stankevich BA, et al. Sex differences in the pharmacokinetics and pharmacodynamics of antidepressants: an updated review. Gend Med. 2009;6(4):522–543. PubMed CrossRef
Soldin OP, Chung SH, Mattison DR. Sex differences in drug disposition. J Biomed Biotechnol. 2011;2011:187103. CrossRef
Hildebrandt MG, Steyerberg EW, Stage KB, et al. Are gender differences important for the clinical effects of antidepressants?. Am J Psychiatry. 2003;160(9):1643–1650.
Ronfeld RA, Tremaine LM, Wilner KD. Pharmacokinetics of sertraline and its N-demethyl metabolite in elderly and young male and female volunteers. Clin Pharmacokinet. 1997;32(Suppl 1):22–30. CrossRef
Sramek JJ, Murphy MF, Cutler NR. Sex differences in the psychopharmacological treatment of depression. Dialogues Clin Neurosci. 2016;18(4):447–457.
Novick D, Montgomery W, Moneta V, et al. Antidepressant medication treatment patterns in Asian patients with major depressive disorder. Patient Prefer Adherence. 2015;9:421–428.
López E, Steiner AJ, Manier K, et al. Quality of life and functioning of Hispanic patients with Major Depressive Disorder before and after treatment. J Affect Disord. 2018;225:117–122. PubMed CrossRef
Milosavljevic F, Bukvic N, Pavlovic Z, et al. Association of CYP2C19 and CYP2D6 poor and intermediate metabolizer status with antidepressant and antipsychotic exposure: a systematic review and meta-analysis. JAMA Psychiatry. 2021;78(3):270–280.
Brouwer JMJL, Wardenaar KJ, Nolte IM, et al. Association of CYP2D6 and CYP2C19 metabolizer status with switching and discontinuing antidepressant drugs: an exploratory study. BMC Psychiatry. 2024;24(1):394. CrossRef
National Institutes of Health. National Institutes of Health Minority Health and Health Disparities Strategic Plan 2021-2025. 2021. Accessed March 26, 2026. https://www.nimhd.nih.gov/about/strategic-plan
Stephenson J. FDA offers guidance for boosting diversity in clinical trials. JAMA Health Forum. 2020;1(11):e201434.
US Food and Drug Administration. Prescription Drug User Fee Amendments; 2026. Accessed March 26, 2026. https://www.fda.gov/industry/fda-user-fee-programs/prescription-drug-user-fee-amendments
Brody DJ, Gu Q. Antidepressant Use Among Adults: United States, 2015-2018. 2020. Accessed March 26, 2026. https://www.cdc.gov/nchs/products/databriefs/db377.htm
George S, Duran N, Norris K. A systematic review of barriers and facilitators to minority research participation among African Americans, latinos, Asian Americans, and Pacific islanders. Am J Public Health. 2014;104(2):e16–e31. PubMed CrossRef