Anti-inflammatory treatment and risk for depression after first-time stroke in a cohort of 147 487 Danish patients

Background: Depression is a common complication after stroke, and inflammation may be a pathophysiological mechanism. This study examines whether anti-inflammatory treatment with acetylsalicylic acid (ASA), nonsteroid anti-inflammatory drugs (NSAIDs) or statins influence the risk of depression after stroke. Methods: A register-based cohort including all patients admitted to hospital with a first-time stroke from Jan. 1, 2001, through Dec. 31, 2011, and a nonstroke population with a similar age and sex distribution was followed for depression until Dec. 31, 2014. Depression was defined as having a hospital contact with depression or having filled prescriptions for anti-depressant medication. The associations between redeemed prescriptions of ASA, NSAIDs or statins with early- (≤ 1 year after stroke or study entry) and late-onset (> 1 year after stroke or study entry) depression were analyzed using Cox proportional hazard regression. Results: We identified 147 487 patients with first-time stroke and 160 235 individuals without stroke for inclusion in our study. Redeemed prescriptions of ASA, NSAIDs or statins after stroke decreased the risk for early-onset depression, especially in patients with ischemic or severe stroke. Patients who received a combination of anti-inflammatory treatments had the lowest risk for early-onset depression. On the other hand, use of ASA or NSAIDs 1 year after stroke increased the risk for late-onset depression, whereas statin use was associated with a tendency toward a decreased risk. Limitations: The study used prescription of antidepressant medication as a proxy measure for depression and did not include anti-inflammatory drugs bought over the counter. Conclusion: Anti-inflammatory treatment is associated with a lower risk for depression shortly after stroke but a higher risk for late depression. This suggests that inflammation contributes differently to the development of depression after stroke depending on the time of onset.