Should adherence to antidepressants be judged in isolation in ischaemic heart disease?

We read the article by Krivoy et al, ¹ addressing an important clinical issue of medication adherence, especially antidepressants in patients with ischaemic heart disease, and its impact on mortality rates. The authors must be congratulated for evaluating the data of such a large sample after controlling for many known covariates. However, there are certain issues which require clarification, before accepting the 1:1 relationship of adherence to antidepressants only and reduced mortality rate.

First, it is unlikely that the patients would be adherent or non-adherent to antidepressants in isolation; hence, it is possible that those who were adherent to antidepressants were also adherent to other medications and this overall adherence to medications led to reduction in mortality rates. As a result, there is a need to provide the data in terms of adherence to other medications and include these as a covariate. Second, with such a large sample size, the authors should have evaluated the effect of each antidepressant or class of antidepressant on mortality. This is important from a clinical practice point of view, because this could have provided information about which antidepressants are more useful. Third, for assessing the confounding effect of comorbidity, the authors used the Charlson comorbidity index, which is considered to be a good predictive marker for mortality. However, it is important to note that the index does not take dyslipidaemia into account. Accordingly, a covariate which is an important risk factor for mortality in patients with ischaemic heart disease could have been left out. Fourth, certain other covariates that can also influence mortality, for example alcohol use or dependence, were not taken into account. Fifth, although the authors have acknowledged that information on causes of death was not evaluated, it remains an important limitation. Sixth, the authors have not evaluated the prescribed doses in terms of being in the therapeutic range or not. This is important because antidepressants such as amitriptyline and duloxetine are prescribed by physicians at lower doses for indications other than depression or anxiety. Seventh, in the study, about three-quarters of patients were aged 65 years or older, with 38% of the study sample aged more than 74 years. If it is presumed that many of these patients were dependent on others for intake and purchasing of the medication, this should also be evaluated. Last, adherence to antidepressants was assessed in terms of medication possession ratio. In real terms this does not suggest that patients would have taken all the doses which they purchased. It is often a clinical experience that although patients purchase the prescribed medications, they do not take all the purchased medications. Consequently the authors would have overestimated the medication adherence.