Specific Serotonin Reuptake Inhibition in Major Depressive Disorder Adversely Affects Novel Markers of Cardiac Risk

Abstract

There exists a growing body of evidence linking depression with cardiovascular events, although the mechanisms responsible remain unknown. We investigated the role of the autonomic nervous system and inflammation in the link between coronary heart disease and major depressive disorder (MDD), and examined the cardiac risk modification following pharmacological treatment of depression. We measured cardiac baroreflex function, heart rate variability, pulse pressure and high sensitivity C-reactive protein (hsCRP), all of which have an impact on cardiac risk, pre-and post-treatment in 25 patients with MDD, with no history of coronary heart disease, and in 15 healthy subjects. Treatment consisted of selective serotonin reuptake inhibitors for approximately 12 weeks. No significant differences were observed between untreated MDD patients and healthy subjects in blood pressure, heart rate, baroreflex sensitivity or heart rate variability.Pulse pressure and hsCRP, however, were significantly elevated in patients with MDD prior to treatment (p =0.023 and p =0.025, respectively). Moreover, while pharmacotherapy was effective in alleviating depression, surprisingly, each of cardiac baroreflex function, heart rate variability, pulse pressure and hsCRP was modified (p <0.05) in a manner likely to increase cardiac risk. In conclusion, this study demonstrated higher pulse pressure and hsCRP plasma levels in patients with MDD, which might contribute to increased cardiac risk. Following treatment vagal activity was reduced, as indicated by reductions in baroreflex sensitivity and heart rate variability, accompanied by increases in pulse pressure and plasma hsCRP levels. Mechanisms potentially responsible for generating cardiac risk in patients treated with selective serotonin reuptake inhibitors may need to be therapeutically targeted to reduce the incidence of coronary heart disease in this pop-

Depression and Blood Pressure Control: All Antidepressants Are not the Same

“…We have previously documented a reduction in vagal activity, as indicated by a diminution in heart rate variability and baroreflex sensitivity, in patients with depression after serotonin-specific reuptake inhibitor therapy. 2 Moreover, Licht et al, 3 in an earlier analysis of data from the Netherlands Study of Depression and Anxiety, documented a reduction in heart rate variability in patients with depression. The association between diminished heart rate variability and depression was driven largely by the use and dose of antidepressants.…”

Autonomic nervous system dysfunction in psychiatric disorders and the impact of psychotropic medications: a systematic review and meta-analysis

“…In total, 140 case-control and 30 treatment 76,83,93,110,116,129,138,141,155,175,[187][188][189][190][191][192][193][194][195][196][197][198][199][200][201][202][203][204][205][206] studies were eligible for inclusion in the quantitative synthesis (151 case-control and 43 effect sizes for analysis); 10 of the studies were included in both the case-control and treatment analyses. 76,83,93,110,116,129,138,141,155,175 Four subgroups of disorders (mood, anxiety-related, psychotic and substance dependence disorders) and 2 classes of psychotropic medications (antidepressants and antipsychotics) were included. Table 1 reports study characteristics for case-control and treatment studies, separated by diagnostic group or type of psychotropic medication, respectively (see Appendix 1, Tables S1 and S2, for individual study characteristics).…”

“…Bär et al 189 Davidson et al 190 188 Dawood et al 110 Khaykin et al 191 Koschke et al 116 Lederbogen et al 192 Prasko et al 76 Rechlin 194 Rechlin 194 Rechlin et al 196 Tucker et al 83 Udupa et al 197 Udupa et al 198 Yeragani et al 201 189 Khaykin et al 191 Lederbogen et al 192 McLeod et al 193 Rechlin 194 Rechlin et al 195 Rechlin et al 195 Rechlin et al 196 Tulen et al 129 Udupa et al 198 Yeragani et al 199 Yeragani et al 200 …”

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

“…A single study reported opposite findings (Dawood et al 2007). A meta-analysis reported a marginally significant decrease in CRP after anti-depressant treatment (Hiles et al 2012), while higher CRP levels at baseline were found to predict the persistence of depressive symptoms over 5 years (Zalli et al 2015).…”