Physicians, be careful with self-exclusion of depressed and anxious patients from clinical trials!

Abstract

Both the invited editorial by Cattadori et al. and the article by Gronhoj et al. published in a previous issue of the European Journal of Preventive Cardiology discuss the fact that the population studied in clinical trials is different from that seen in hospital wards. In particular, they underline the frequent exclusion from clinical trials of female, elderly people and patients with comorbidities. These subjects are usually excluded despite the fact that literature identify them as categories at high risk of heart failure. Clinical trials also do not take into account cultural and socio-economical aspects that are important determinants of the prognosis of many kinds of illnesses. In particular, as described in the article by Gronhoj et al., there is a significant self-exclusion from clinical trials of people with higher comorbidities and lower socio-economic status. However, we cannot ignore that there is another significant category of patients who prefer not to participate to clinical trials. We are referring to depressed and anxious people. Usually being risk averse, depressed patients are overly cautious in their health choices in general, and in clinical trial participation in particular, choosing to give up possible valuable care options in the attempt to avoid the risk of additional burdens and/ or adverse effects. A significant inverse correlation has also been observed between the presence of traitanxiety and social avoidance behaviours, and voluntary participation in phase I studies. Considering these two psychological variables (depression and anxiety), it appears that participants in clinical trials are a selfselected sample characterised by no depression, low trait-anxiety and low social avoidance behaviours. This self-selection is even more evident in the presence of clinical conditions in which patients experience an emotional whirlwind that makes them particularly vulnerable to cognitive biases with possible negative consequences on their decisions. The importance of finding effective strategies to limit this self-exclusion phenomenon, especially in cardiovascular trials, is strongly supported by the following evidence: (a) depression and cardiovascular diseases are actually two of the most common diseases in industrialised areas; (b) they often appear in comorbidity; and (c) cardiac patients are 3–4 more times at risk of developing depressive and anxiety disorders compared to the general population. Since systematic data from real clinical environments are scarce, a few months ago we started a psychological screening on the patients consecutively admitted in a cardiologic hospital in the north of Italy. In nine months we collected data from 1400 patients (954 males and 446 females, aged between 17–95 years; mean1⁄4 64.25, standard deviation (SD)1⁄4 14.43) and found that 9.3% of them had a score higher than 10 in the Patient Health Questionnaire-9 (PHQ9) questionnaire (cut-off for mild depression) and 33.5% of them had a score higher than five in the Generalized Anxiety Disorder-7 (GAD7) questionnaire (cut-off for mild anxiety). These data confirm a higher incidence of depression and anxiety in cardiac patients compared to the general population. Even more worrying are the data emerging from another ongoing study including 1050 healthy individuals, aged between 19–89 years (mean1⁄4 54.38, SD1⁄4 10.80) showing significant negative correlations between the spontaneous choice of undergoing regular preventive health screening (at least one per year) and the presence of depression (r1⁄4 0.112, p< 0.001), anxiety (r1⁄4 0.099, p< 0.001) and perceived stress (r1⁄4 0.138, p< 0.001). Avoiding prevention, such individuals are at higher risk of developing future illnesses (including cardiovascular diseases) compared to those who perform regular screening. The inclusion of a greater number of such patients and the characterization of participant’s depression and