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Abstract
BackgroundMajor depressive disorder (MDD) constitutes the leading cause of disability worldwide. Although efficacious antidepressant pharmacotherapies exist for MDD, only about 40–60% of the patients respond to initial treatment. However, there is still a lack of robustly established and applicable biomarkers for antidepressant response in everyday clinical practice.ObjectiveThis study targets the assessment of the vasopressin (AVP) surrogate marker Copeptin (CoP), as a potential peripheral hypothalamic-level biomarker of antidepressant treatment response in MDD.MethodsWe measured baseline and dynamic levels of plasma CoP along with plasma ACTH and cortisol (CORT) in drug-naive outpatients with MDD before and after overnight manipulation of the hypothalamic-pituitary-adrenal (HPA) axis [i.e., stimulation (metyrapone) and suppression (dexamethasone)] on three consecutive days and their association with treatment response to 4 weeks of escitalopram treatment.ResultsOur findings suggest significantly higher baseline and post-metyrapone plasma CoP levels in future non-responders, a statistically significant invert association between baseline CoP levels and probability of treatment response and a potential baseline plasma CoP cut-off level of above 2.9 pmol/L for future non-response screening. Baseline and dynamic plasma ACTH and CORT levels showed no association with treatment response.ConclusionsThis pilot study provide first evidence in humans that CoP may represent a novel, clinically easily applicable, endocrine biomarker of antidepressant response, based on a single-measurement, cut-off level. These findings, underline the role of the vasopressinergic system in the pathophysiology of MDD and may represent a significant new tool in the clinical and biological phenotyping of MDD enhancing individual-tailored therapies.
Highlights
Major depressive disorder (MDD) is a debilitating disease of high lifetime prevalence and constitutes worldwide the leading cause of disability due to chronic disease burden as it is significantly associated with a broad range of physical co-morbidities and higher overall mortality [1,2,3]
Only about 40–60% of the patients respond to initial antidepressant therapy, while only approximately a third will reach remission and about 30–40% may experience treatment resistance even when receiving optimal antidepressant treatment according to consensus guidelines [6,7,8]
Given that assessment of the vasopressin (AVP) is not considered a valid biomarker in MDD and psychiatric disorders in general [28], our results offer first evidence that plasma CoP may represent an alternative stable, accessible, and clinically applicable peripheral biomarker of antidepressant treatment response in MDD
Summary
Major depressive disorder (MDD) is a debilitating disease of high lifetime prevalence and constitutes worldwide the leading cause of disability due to chronic disease burden as it is significantly associated with a broad range of physical co-morbidities and higher overall mortality [1,2,3]. Besides some general negative clinical and psychosocial predictors of non-response [12], there is a lack of objective, individualized, and applicable biomarkers able to distinguish pathophysiological subgroups of depressed patients with different response to antidepressant treatment in everyday clinical practice [13]. Efficacious antidepressant pharmacotherapies exist for MDD, only about 40–60% of the patients respond to initial treatment. There is still a lack of robustly established and applicable biomarkers for antidepressant response in everyday clinical practice
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