Abstract
Abnormal hypothalamic-pituitary-adrenal (HPA) axis has been implicated in major depressive disorder (MDD). A number of studies have attempted to use HPA-modulating medications to treat depression. However, their results are inconsistent. The efficacy of these drugs for MDD remains uncertain. The aims of this meta-analysis were to determine the effect and safety profile of HPA-targeting medications for MDD. World of Science and PubMed databases were comprehensively searched up to March 2021. All randomized controlled trials (RCTs) and open-label trials exploring antiglucocorticoid and related medications in patients with depression were included. Standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for continuous or dichotomous outcomes, respectively. In the meta-analysis, we identified 16 RCTs and seven open-label studies that included 2972 subjects. Pooling the change data that assessed the efficacy across all included HPA-targeting medications for depression showed a significant difference between interventions and controls with very small heterogeneity after influence analysis (SMD = 0.138, 95%CI = 0.052, 0.224, p = 0.002; I2 = 20.7%, p = 0.212). No obvious publication bias was observed (p = 0.127). Effectiveness remained significant in patients with MDD (SMD = 0.136, 95%CI = 0.049, 0.223, p = 0.002). Subgroup analysis showed a significant difference favoring mifepristone and vasopressin 1B (V1B) receptor antagonist treatment. Adverse events were reported by 14 studies and our analysis of high-quality studies showed a significant difference in favor of controls (RR = 1.283, 95%CI = 1.134, 1.452, p = 0). Our study suggested that patients with MDD may benefit from mifepristone and V1B receptor antagonist treatments that have tolerable side effects. HPA-based medications are promising for depression treatment. However, additional high-quality RCTs, including head-to-head trials, are needed.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier registration number: CRD42021247279
Highlights
Major depressive disorder (MDD) is a common and costly mental disorder that is characterized by pervasive low mood and various other symptoms, such as cognitive and physical symptoms
Our study suggested that patients with MDD may benefit from mifepristone and Vasopressin 1 B (V1B) receptor antagonist treatments that have tolerable side effects
Studies investigating Vasopressin 1 B (V1B) receptor antagonists and corticotropin-releasing hormone (CRH) receptor antagonists all focused on MDD
Summary
Major depressive disorder (MDD) is a common and costly mental disorder that is characterized by pervasive low mood and various other symptoms, such as cognitive and physical symptoms. 30% of individuals with MDD always have symptoms present and develop a chronic condition that is reliant on the illness stage and other risk factors such as childhood trauma and personality (Angst et al, 2009; Boschloo et al, 2014). It substantially affects an individual’s psychosocial functioning and exhausts quality of life (Malhi and Mann, 2018). The Sequenced Treatment Alternatives to Relieve Depression study (www.star-d.org) has shown that approximately half of patients with nonpsychotic MDD respond to level 1 antidepressant treatment (citalopram), and only nearly 30% patients achieve remission. Probing into the pathophysiology of MDD and customizing effective therapeutic strategies for every individual suffering from MDD are essential
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