Exploring the relationship between atenolol use and depression: A network pharmacology approach using NHANES data

J Affect Disord. 2025 Nov 15:389:119675. doi: 10.1016/j.jad.2025.119675. Epub 2025 Jun 16.

Abstract

Background: Atenolol, a β-blocker, offers significant cardiovascular benefits, but its potential association with depression remains unclear.

Objective: The goal of this study is to investigate the relationship between atenolol use and depression, exploring underlying mechanisms through network pharmacology.

Method: Data from 11,057 adult participants in the NHANES database (2005-2018) were analyzed. Participants were categorized by their use of atenolol, and depression levels were evaluated using the PHQ-9 scale. Logistic regression was used to analyze the association between atenolol use and depression. Additionally, network pharmacology methods were used to identify potential targets and pathways related to the neuropsychiatric effects of atenolol.

Results: A significant link was observed between atenolol use and depression (OR = 2.02, 95 % CI: 1.13-3.59) in the fully adjusted model, with a stronger association in the 40-64 years age group. Network pharmacology identified 19 core targets related to depression, including MAOB, ADRB2, DRD2, and SLC6A3, which showed strong binding affinities with atenolol. Enrichment analysis suggested that atenolol may influence the onset of depression by modulating biological processes such as G protein-coupled receptor signaling and monoamine transport.

Conclusions: Our findings indicate a positive correlation between atenolol use and depression, particularly among individuals in the middle-aged demographic. It is important to monitor the mental health of patients when prescribing atenolol.

Keywords: Atenolol; Depression; NHANES; Network pharmacology.

MeSH terms

  • Adult
  • Aged
  • Atenolol* / adverse effects
  • Depression* / chemically induced
  • Depression* / epidemiology
  • Dopamine Plasma Membrane Transport Proteins / drug effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Network Pharmacology
  • Nutrition Surveys
  • United States / epidemiology

Substances

  • Atenolol
  • Dopamine Plasma Membrane Transport Proteins