To our knowledge, this systematic review and meta-analysis is the first to focus specifically on the association between depression and medication adherence, analyze a sufficient number of studies to safely address the risk of publication bias, include studies of hypertension and hyperlipidemia, and investigate important potential moderators of the association. We found that depressed patients had 1.76 times the odds of being non-adherent compared to patients who were not depressed, across 31 studies and 18,245 participants.
These results were moderated by the method of adherence measurement. We found that using pharmacy records to assess medication adherence resulted in a significantly smaller correlation coefficient between depression and adherence compared to using self-report methods. The reason for this difference is not clear. Some have suggested that patients with depression may be more likely to self-report higher non-adherence than those without depression, in the setting of similar levels of actual medication-taking. 46,47
It is possible that pharmacy claims, which are objective measures of prescription filling, would not be subject to this reporting bias, although our analysis did not find any difference in the effect of depression between electronic monitoring studies and self-report. While pharmacy claims measure only the quantity of medications dispensed, it is also possible that self-reported adherence would capture other behaviors which may not be visible to claims and may be more susceptible to the effects of depression, such as incorrectly-timed doses or not ingesting filled medications. The variable concordance between the different measures of medication adherence, 28,48
and the heterogeneity of outcome measurement in these studies makes it difficult to draw firm conclusions; nonetheless, this finding suggests that future research in this area would benefit from including multiple methods of assessing adherence.
Other potential moderators did not reach statistical significance, including study size, depression assessment method, statistical methodology, or importantly, disease category (diabetes, hyperlipidemia/hypertension, and other). The consistent effect size across disease categories suggests that depression’s effects on adherence could be independent of each chronic disease’s treatment characteristics; while we are not able to draw definitive conclusions about how this finding might affect future research or interventions, lessons learned about the role of depression in adherence in diabetes, for example, could be applied to other chronic conditions.
The association between depression and medication adherence has important implications for clinical practice and quality of care for chronic diseases. Depression, as a diagnosis and as a set of symptoms, is extremely common in the US, with a 12-month national prevalence of approximately 6% and a lifetime prevalence of 13-16%. 49,50
Depression is common among those over age 65, who bear the burden of chronic diseases for which medication adherence is critical, 51
and there is evidence that depression is associated with adverse outcomes for several diseases, including coronary heart disease and diabetes. 52,53
Identifying depressed patients as being at high risk for medication non-adherence should be standard of care after decades of research. Alternatively, because the direction of the effect is not totally clear, medication non-adherence may be a marker for depression; suspected patient non-adherence would thus be an opportunity to screen for and discuss depression, which may be undiagnosed.
It is important to remember that depression is just one barrier known to affect medication adherence. Well-documented barriers include dose complexity and cost sharing. 54–56
Other barriers with research support include beliefs about medications, social support, side effects, and provider factors, among others. 57
Clinicians should be mindful of these barriers and be aware of recent reviews on interventions that may help improve adherence. 17,18,58,59
We are unable to comment on barriers to adherence for diseases excluded from this review such as HIV, although it should be noted that prior reviews have found depression to be a barrier to antiretroviral adherence 60,61
There are several possible limitations in this study. First, meta-analysis results are correlational, providing limited opportunities to assess causality or identify confounders that could explain the apparent association between depression and poor adherence. A second limitation is the heterogeneity among the studies of assessment methodologies, participant characteristics, comparison groups, and statistical analyses methods. For example, patients with hypertension and hyperlipidemia constituted a large portion of the participants in the studies. Fortunately, however, our findings are supported by prior meta-analyses and our statistical methods partially account for the heterogeneity. A third limitation is the possibility of publication bias. In the current study, however, the number of unpublished studies with null effect would have to be quite large to change the outcome. The two largest included studies, in fact, found null effects, and yet the meta-analysis overall found a strong relationship between depression and adherence. Finally, it is possible that we missed some studies that have been published on medication adherence due to our selection of search terms.