Associations of Cardiovascular Agents and Metformin with Depression Symptoms: A Cross-Sectional Analysis from the HUNT Study, Norway

Background: Cardiovascular agents, including angiotensin-converting enzyme inhibitors, angiotensin II receptor inhibitors, acetylsalicylic acid, statins, and metformin, have demonstrated benefits for depression. However, there is scant evaluation of these drugs’ antidepressant properties in large population settings. Objective: This study aimed to examine cross-sectional associations between depression symptoms and the use of cardiovascular agents and metformin in populations with cardiovascular diseases or diabetes mellitus. Methods: Participants in the Trøndelag Health Study 2006–08 (HUNT3, n = 40,516) and 2017–19 (HUNT4, n = 42,103) were included and data on their drug use from 2006 to 2019 was retrieved from the Norwegian Prescription Database. The outcome was self-reported depression symptoms defined by the Hospital Anxiety and Depression Scale. Associations between cardiovascular agents or metformin use and self-reported depression were analyzed by multi-level logistic regression in sex-stratified samples. Results: Among men with cardiovascular diseases, use of acetylsalicylic acid was associated with reduced depression symptoms compared with acetylsalicylic acid non-users (reference) in HUNT3 and HUNT4 [risk ratio = 0.76; 95% confidence interval 0.59–0.94, risk ratio = 0.67; 95% CI 0.52–0.82, respectively]. Similarly, male statin users had a lower likelihood of reporting depression than statin non-users in HUNT3 (risk ratio = 0.70; 95% confidence interval 0.54–0.86) and HUNT4 (risk ratio = 0.67; 95% confidence interval 0.51–0.84). Associations between statins or acetylsalicylic acid use and reduced depression symptoms were detected in women with cardiovascular diseases in HUNT4. We found no statistical support for associations between other cardiovascular agents or metformin use and a reduced or increased depression symptom risk. Conclusions: Results suggest negative associations between acetylsalicylic acid or statin use and depression symptoms. However, longitudinal cohort studies and randomized controlled trials are required to confirm the antidepressant effects of these drugs.