Differential Changes in Autonomic Functioning, Hypothalamic–Pituitary–Adrenal Axis Activity and Inflammation during Melatonergic Antidepressant Treatment between Depressed Patients with and without Suicidal Ideation

Objective: The existing literature has not yet simultaneously examined the modification of autonomic functioning, hypothalamic–pituitary–adrenal (HPA) axis activity and inflammation following agomelatine treatment of depression. We investigated the changes in the three biological systems that are closely linked to cardiovascular risks among depressed patients with/without suicidal ideation (SI) following agomelatine treatment. Methods Thirty-two unmedicated depressed patients with current SI (SI+ group) and 28 without current/lifetime SI (SI− group) completed 6-week agomelatine treatment. None of them had any current or lifetime suicidal behavior before entering the study. The peripheral levels of cortisol, erythrocyte sedimentation rate (ESR) and high sensitivity C-reactive protein (hs- CRP), and heart rate variability (HRV) were measured at baseline and week 6. The Hamilton Depression Rating Scale (HAM-D) and the Columbia Suicide Severity Rating Scale (C-SSRS) were assessed at baseline, week 2, 4 and 6. Results Between-group analyses showed a significant treatment-by-group interaction for cortisol, ESR, hs-CRP, the ratio of cortisol to hs-CRP (COR/CRP ratio), variance (total HRV), low frequency (LF)-HRV, and high frequency (HF)-HRV. The results were driven by decreases in cortisol, hs- CRP and ESR levels and increases in total HRV, LF-HRV and HF-HRV in the SI+ group, coupled with an increase in hs-CRP levels and a decrease in COR/CRP ratio in the SI− group. Moreover, in the SI+ group the lessening of the intensity of SI independently predicted the reduction in hs-CRP levels. Conclusions Agomelatine treatment differentially modified biomarkers of cardiac risk between depressed patients with current SI and those without SI. The specificity and underlying mechanism of melatonergic antidepressant beneficially affecting markers of cardiac risk in only depressed patients with current SI merits further investigation. Peripheral hs-CRP levels may serve as a potential tool to monitor the fluctuation of SI in depressed patients under agomelatine treatment.