Does lisinopril cause depression
Pro Research Analysisby 
Searched over 200M research papers
Lisinopril and Depression: Analyzing the Evidence
Introduction to Lisinopril and Its Uses
Lisinopril is a widely prescribed angiotensin-converting enzyme inhibitor (ACEI) primarily used to manage hypertension and heart failure. Given its extensive use, understanding its potential side effects, including any impact on mental health, is crucial.
Lisinopril's Potential Antidepressant Effects
Rapid Mood-Elevating Properties
Recent research has explored the potential antidepressant effects of ACEIs, including lisinopril. Studies have shown that ACEIs may have a rapid mood-elevating effect in certain patients. For instance, experimental studies on animal models have demonstrated that lisinopril can exert a fast and long-lasting antidepressant effect. This effect appears to be mediated through the bradykinin (BK) system rather than the renin-angiotensin system, suggesting a novel mechanism of action for these drugs in treating depressive symptoms.
Mechanism of Action
The antidepressant effects of lisinopril are thought to involve the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway. This pathway is crucial for cellular growth and synaptic plasticity, which are often impaired in depression. By reversing the stress-induced loss of dendritic spines through the BK system, lisinopril may help alleviate depressive-like behaviors.
Comparative Studies on Depression Rates
Observational Cohort Studies
A large-scale observational study assessed the rates of depression among patients using various cardiovascular agents, including lisinopril. The study found that the crude overall rates of depression during treatment with ACE inhibitors, including lisinopril, were comparable to those observed with calcium channel blockers. Specifically, the rates of depression were 1.89 per 1000 patient months for ACE inhibitors, which was not significantly different from the rates observed with calcium channel blockers like diltiazem and nicardipine.
Statistical Analysis
The rate ratios for depression when using ACE inhibitors as the reference group were 1.07 for diltiazem and 0.86 for nicardipine, indicating no significant increase in depression risk with these medications compared to ACE inhibitors. This suggests that lisinopril does not have a higher association with depression compared to other cardiovascular drugs.
Conclusion
Current evidence suggests that lisinopril may not cause depression and might even have potential antidepressant effects through mechanisms involving the bradykinin system and mTORC1 pathway activation. Observational studies further support that the rates of depression in patients using lisinopril are not significantly different from those using other cardiovascular agents. Therefore, lisinopril appears to be a safe option for patients concerned about depression, with the added potential benefit of mood elevation in some cases.
Sources and full results
Most relevant research papers on this topic