Worldwide, depression and bipolar disorder affect a large and growing number of people. However, current pharmacotherapy options remain limited. Despite adequate treatment, many patients continue to have subsyndromal symptoms, which predict relapse in bipolar illness and often result in functional impairments. Aspirin, a common nonsteroidal anti-inflammatory drug (NSAID), has purported beneficial effects on mood symptoms, showing protective effects against depression in early cohort studies. This systematic review thus aimed to investigate the role of aspirin in mood disorders. Using the keywords (aspirin or acetylsalicy* or asa) and (mood or depress* or bipolar or mania or suicid*), a comprehensive search of PubMed, EMBASE, Medline, PsycINFO, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), Clinicaltrials.gov and Google Scholar databases found 13,952 papers published in English between 1 January 1988 and 1 May 2019. A total of six clinical studies were reviewed. There were two randomized, placebo-controlled, double-blind trials and populations drawn from two main cohort studies (i.e., the Geelong Osteoporosis Study and the Osteoarthritis Initiative study). Using a random-effects model, the pooled hazard ratio of the three cohort studies was 0.624 (95% confidence interval: 0.0503 to 1.198, p
= 0.033), supporting a reduced risk of depression with aspirin exposure. Overall, the dropout rates were low, and aspirin appears to be well-tolerated with minimal risk of affective switch. In terms of methodological quality, most studies had a generally low risk of bias. Low-dose aspirin (80 to 100 mg/day) is safe, well-tolerated and potentially efficacious for improving depressive symptoms in both unipolar and bipolar depression. Due to its ability to modulate neuroinflammation and central nervous system processes, aspirin may also have valuable neuroprotective and pro-cognitive effects that deserve further exploration. Further randomized, controlled trials involving the adjunctive use of aspirin should be encouraged to confirm its therapeutic benefits.
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