The main finding of this report is that the self-reported rate of starting antidepressant medications varies among several ethnic groups in a US-based, prospective cohort that was unselected for baseline depression. The MESA cohort was formed to look at subclinical cardiovascular disease and the assessment of depression was done as part of an overall assessment of possible cardiovascular risk factors. Using the MESA cohort to study depression is an important strength of this report as it removes any potential stigma for participation in a study targeted at depression (and any such stigma could be reasonably differential by ethnic group).
Of the four ethnicities, Caucasian participants had the highest rate of antidepressant medication use compared with African-American, Asian, and Hispanic participants even after adjusting for differences in depressive symptoms at baseline. This association also persisted after adjusting for differences in loss to follow-up between different ethnicities.
There was evidence of non-random loss to follow up among the MESA participants. It is reasonable to use IPCW estimates as the gold standard for estimating the size of the association as IPCW adjusted estimates are generally less biased in the presence of non-random loss to follow-up than estimates that assume random censoring [16
]. Given this reasonable assumption, we have a percent difference in the log hazard ratio of 17% for African-American participants, 32% for Asian participants, and 31% for Hispanic participants. These are non-ignorable changes in the estimates of the association between ethnicity and new use of antidepressant medications, passing the informal threshold of a 10% change in the estimates that is often used. While the IPCW corrected HRs do not affect the inference involved, they do provide a more accurate estimate of the size of the association.
The reason for this difference in utilization of antidepressant medications between different ethnic groups in the US is unknown. The extent to which these differing levels of antidepressant medication use represent under-treatment, over-treatment or the correct level of treatment is also an open question [1
]. It is worth noting that Caucasian participants in the MESA study have more users of antidepressant medications at lower levels of CES-D score, but this evidence is not strong enough to enable a clear interpretation as to appropriate or inappropriate treatment. Various explanations have been offered to attempt to explain this difference in utilization between ethnic groups, including differential quality of care [22
] or differential stigma associated with the treatment of depression in different ethnic groups [23
We cannot distinguish whether the treatments given were appropriate as the CES-D is not able to definitively diagnose clinical depression [7
] and high scores are considered to be an indicator of possible depression rather than conclusive evidence [8
]. Given the high rate of off-label use of antidepressant medications in US populations [24
], it is likely that some of this antidepressant use may be for indications other than for clinical depression. These off-label uses often include conditions such as headaches, smoking cessation, chronic pain, insomnia, or premenstrual syndrome [25
], the prevalence of which could not be evaluated using the information available from the MESA study. While some of these differences in antidepressant use could be attributed to off-label indications, off-label uses are unlikely to fully explain these large differences. It is also plausible that there could be under-treatment among participants with high CES-D scores while there is over-treatment among participants with low CES-D scores.
The use of IPCW to correct for loss to follow in cohort studies is an established technique used to account for known predictors of non-random loss to follow-up [16
]. Accounting for non-random loss to follow-up is important in the context of this particular outcome as loss to follow-up is associated with both ethnicity and depression. However, the overall effect of the IPCW adjustment did not change the statistical inference suggesting that differential loss to follow-up was not sufficient to explain the observed differences between ethnicity conditional on the covariates observed [16
]. Of course, measurement error and misspecification of the censoring model continue to be threats to study validity even after applying an IPCW correction.
Due to cultural variations, CES-D score distributions can be expected to vary by ethnicity due to different expressions of depression in different ethnicities [26
]. This assumption that the meaning of a given CES-D score is comparable between different ethnic groups underlies the use of this score to correct for different levels of depressive symptoms, and studies that use the score in this manner make this assumption [12
]. While this assumption may not be strictly true, we do not believe that making it in this context poses a major threat to the validity of the study results. The actual effect that these ethnic differences in expression of depression symptoms could have on subsequent antidepressant use is currently unknown. As there are known links between depression and both anxiety [30
] and anger [31
], we included anger and anxiety scales in the analysis. These parameters are correlated with CES-D score in our population: CESD and anger score (r=0.32) and CESD and anxiety (r=0.62). However, neither the anger or anxiety scale had a statistically significant association with increased utilization of antidepressants when CES-D score was also included in the statistical model.
There are limitations to this study that should be considered when interpreting these results. We did not have longitudinal information on depression scores; ideally we would have treated CES-D score as a time-varying confounder instead of a baseline confounder. Our definition of antidepressant medication use relies on a combination of self-report and a medication inventory. It is possible that there could be some degree of under-reporting of medication use by some of the participants in the study. In addition, alternative treatments, such as behavioral activation or cognitive therapy, can show comparable effectiveness to antidepressant use [32
] and differential use of these treatment options by ethnicity could also partially explain some of the observed differences.
This association between ethnicity and antidepressant medication utilization among MESA participants provides further evidence that antidepressant use varies by ethnicity independent of CES-D score and other known risk factors. This appears to be an especially strong among the Asian participants in the study, matching previous findings that the lowest utilization of antidepressant drugs in the United States is among persons of Asian ethnic origin [2
]. However, the strength of this association is likely to be overestimated in prospective cohort studies if non-random loss to follow-up is not considered.