The higher prevalence and cost of depression for women compared with men and the possible gender differences in treatment response demand the inclusion of women in clinical trials of depression treatments. The 1993 National Institutes of Health (NIH) Revitalization Act set a new standard, requiring investigators to consider the inclusion of women and analyze outcomes by gender, yet compliance with these standards in depression research has not been examined systematically. The purpose of this study is to examine the inclusion of women and gender-specific analyses in recent randomized clinical trials (RCTs) for depression.
Methods:
RCTs were identified through a MEDLINE search for trials published between January 1 and December 31, 2007, and a Clinicaltrials.gov search of self-identified interventional studies to treat depression.
Results:
Of the 150 RCTs for depression published in 2007, 15% did not report the gender composition of their sample, 50% of studies did not analyze outcomes by gender, and 12% controlled for gender but did not analyze for gender differences. Of the 768 trials reviewed on Clinicaltrials.gov, 89% reported recruiting male and female participants, yet <1% reported an intention to analyze results by gender.
Conclusions:
Many recent studies of depression treatments include women but do not examine outcomes by gender. Understanding how women differ from men in response to treatment is critical for enhancing treatment efficacy for the greatest number of adults with depression.
Get full access to this article
View all access options for this article.
References
1.
MastroianniAC, FadenR, FedermanD. Committee on the Ethical and Legal Issues Relating to the Inclusion of Women in Clinical Studies. Women and health research: Ethical and legal issues of including women in clinical studies. Washington, DC: National Academy Press, 1994; 1.
2.
United States Public Health Service. Report of the Public Health Service Task Force on Women's Health issues. Public Health Rep, 1985; 100:73–106.
3.
National Institutes of Health. NIH guide for grants and contracts. Bethesda, MD: National Institutes of Health, 1986.
4.
General Accounting Office. Problems in implementing policy on women in study populations. Washington DC: United States Government Accounting OfficeReport No. GAO/T-HRD-90-501990.
5.
Federal Register. NIH guidelines on the inclusion of women and minorities as subjects in clinical research, 1994; 59.
6.
Food and Drug—Administration. Guidelines for the study and evaluation of gender differences in the clinical evaluation of drugs. U.S. Federal Register, 1993; 58:39406–39416.
7.
VidaverRM, LaFleurB, TongC, BradshawR, MartsSA. Women subjects in NIH-funded clinical research literature: Lack of progress in both representation and analysis by sex. J Womens Health Gend Based Med, 2000; 9:495–504.
8.
RamasubbuK, GurmH, LitakerD. Gender bias in clinical trials: Do double standards still apply?J Womens Health Gend Based Med, 2001; 10:757–764.
9.
General Accounting Office. Women's health: NIH has increased its efforts to include women in research. Washington, DC: United States General Accounting Office, 2000.
10.
GellerSE, Goldstein AdamsM, CarnesM. Adherence to federal guidelines for reporting of sex and race/ethnicity in clinical trials. J Womens Health, 2006; 15:1123–1131.
11.
FleischJ, FleischMC, ThurmannPA. Women in early-phase clinical drug trials: Have things changed over the past 20 years?Clin Pharmacol Ther, 2005; 78:445–452.
12.
BlauwetLA, HayesSN, McManusD, RedbergRF, WalshMN. Low rate of sex-specific result reporting in cardiovascular trials. Mayo Clinic Proc, 2007; 82:166–170.
13.
DickersonDL, LeemanRF, MazureCM, O'MalleySS. The inclusion of women and minorities in smoking cessation clinical trials: A systematic review. Am J Addict, 2009; 18:21–28.
14.
CranePB, LetvakS, LewallenL, HuJ, JonesE. Inclusion of women in nursing research (1995–2001)Nurs Res, 2004; 53:237–242.
15.
KesslerRC, BerglundP, DemlerOet al.National Comorbidity Survey Replication. The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication (NCS-R)JAMA, 2003; 289:3095–3105.
16.
GormanJM. Gender differences in depression and response to psychotropic medication. Gen Med, 2006; 3:93–109.
17.
KlermanGL, WeissmanMM. The course, morbidity, and costs of depression. Arch Gen Psychiatry, 1992; 49:831–834.
18.
BroadheadWE, BlazerDG, GeorgeLK, TseCK. Depression, disability days, and days lost from work in a prospective epidemiologic survey. JAMA, 1990; 2524–2528.
19.
WangPS, SimonGE, KesslerRC. Making the business case for enhanced depression care: The National Institute of Mental Health-Harvard work outcomes research and cost-effectiveness study. J Occup Environ Med, 2008; 50:468–475.
20.
LuppaM, HeinrichS, AngermeyerMC, KonigHH, Riedel-HellerSG. Cost-of-illness studies of depression: A systematic review. J Affect Disord, 2007; 98:29–43.
21.
GreenbergPE, KesslerRC, BirnbaumHGet al.The economic burden of depression in the United States: How did it change between 1990 and 2000?J Clin Psychiatry, 2003; 64:1465–1475.
22.
KesslerRC, McGonagleKA, ZhaeSet al.Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: Results from the National Comorbidity Survey. Arch Gen Psychiatry, 1994; 51:8–19.
23.
GrantBF, HasinDS, ChouP, StinsonFS, DawsonDA. Nicotine dependence and psychiatric disorders in the United States. Arch Gen Psychiatry, 2004; 61:1107–1115.
24.
KesslerRC, McGonagleKA, SwartzM, BlazerDG, NelsonCB. Sex and depression in the National Comorbidity Survey. I: Lifetime prevalence, chronicity and recurrence. J Affect Disord, 1993; 29:85–96.
25.
MeibohmB, BeierleI, DerendorfH. How important are gender differences in pharmacokinetics?Clin Pharmacokinet, 2002; 41:329–342.
26.
YonkersKA, KandoJC, ColeJO, BlumenthalS. Gender differences in pharmacokinetics and pharmacodynamics of psychotropic medication. Am J Psychiatry, 1992; 149:587–595.
27.
KornsteinSG, SchatzbergAF, ThaseMEet al.Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry, 2000; 157:1445–1452.
28.
WohlfarthT, StorosumJG, ElferinkAJ, van ZwietenBJ, FouwelsA, van den BrinkW. Response to tricyclic antidepressants: Independent of gender?Am J Psychiatry, 2004; 161:370–372.
29.
ThielsC, LindenM, GriegerF, LeonardJ. Gender differences in routine treatment of depressed outpatients with the selective serotonin reuptake inhibitor sertraline. Int Clin Psychopharmacol, 2007; 20:1–7.
30.
HildebrandtMG, SteyerbergEW, StageKB, PasschierJ, Kragh-SoerensenP. Danish University Antidepressant Group. Are gender differences important for the clinical effects of antidepressants?Am J Psychiatry, 2003; 160:1643–1650.
31.
YoungEA, KornsteinSG, MarcusSMet al.Sex differences in response to citalopram: a STAR*D report. J Psychiatr Res, 2009; 43:503–511.
32.
ThaseME, ReynoldsCF, FrankEet al.Do depressed men and women respond similarly to cognitive behavior therapy?Am J Psychiatry, 1994; 151:500–505.
33.
PreskornSH. Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet, 1997; 32,Suppl 1:1–21.
34.
MazureCM, KeitaGP. Understanding depression in women: Applying empirical research to practice and policy. Washington, DC: American Psychological Association, 2006.
