Depression is a complex condition affecting many individuals globally. As many do not fully respond to existing therapies, new treatment avenues are constantly explored. This has led to scientific inquiry into various compounds, including aspirin, for their potential influence on mood and depressive symptoms.
The Inflammation Connection to Depression
Chronic low-grade inflammation is increasingly recognized as a factor in the development and persistence of depression. This inflammation involves the immune system remaining slightly activated over time. Individuals with depressive disorders often show elevated levels of inflammatory markers in their blood, such as C-reactive protein (CRP) and interleukin-6 (IL-6).
Approximately a quarter of patients with depression exhibit low-grade inflammation, with over half showing mildly elevated CRP levels. Inflammatory molecules, called cytokines, can cross the blood-brain barrier or signal through the vagus nerve. Once in the brain, they can change how neurons function, affect neurotransmitters like serotonin and dopamine, and alter stress hormone systems. This disruption in brain circuits tied to mood and cognition suggests a theoretical basis for anti-inflammatory interventions.
How Aspirin May Influence Mood
Aspirin, known chemically as acetylsalicylic acid, exerts its anti-inflammatory effects primarily by irreversibly inhibiting cyclooxygenase (COX) enzymes. There are two main forms: COX-1, which maintains normal physiological functions, and COX-2, typically induced by inflammatory stimuli. Aspirin blocks both enzymes by acetylating a specific serine residue in their active sites.
This inhibition prevents the production of prostaglandins and thromboxanes, which are lipid compounds that mediate inflammation, pain, and fever. By reducing the synthesis of these pro-inflammatory mediators, aspirin can lessen the body’s overall inflammatory response. The reduction of systemic and brain inflammation through this mechanism is thought to potentially ameliorate depressive symptoms and influence central nervous system processes.
Current Research on Aspirin for Depression
Research exploring aspirin’s role as a treatment for depression has yielded mixed findings. Some early observational cohort studies suggested a reduced risk of depression among individuals exposed to aspirin. A systematic review also found some evidence supporting low-dose aspirin, typically 80 to 100 mg per day, as potentially efficacious for improving depressive symptoms in both unipolar and bipolar depression.
However, a large-scale, double-blinded, placebo-controlled randomized clinical trial, the ASPREE-Depression study, investigated whether low-dose aspirin (100 mg daily) could prevent depression in healthy older adults. This comprehensive study, involving over 19,000 participants, found no significant differences in depression rates or symptom severity between the aspirin and placebo groups over an average follow-up of 4.7 years. Another study in older individuals even reported a small but significant increase in depressive scores in the aspirin group compared to placebo over time. While preclinical data hinted at antidepressant effects, the most robust trials to date do not support aspirin as a preventative measure for depression in otherwise healthy older adults.
Important Considerations and Risks
Aspirin is a medication with potential side effects and risks, even at lower doses. A notable concern is the increased risk of gastrointestinal bleeding. This risk is elevated for older individuals, those with a history of peptic ulcers, or when aspirin is co-administered with other medications like anticoagulants or other nonsteroidal anti-inflammatory drugs (NSAIDs).
Aspirin is not considered a standalone treatment for depression and should never be taken without direct consultation and supervision from a healthcare professional. Treating depression requires a comprehensive approach, and any medication decisions must be made under expert medical guidance.