Adjunctive Low-Dose Acetylsalicylic Acid in Bipolar Disorder: A Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase II Trial (ASPIRIN BD)

Background/Objectives: Bipolar depression remains difficult to treat. We evaluated the short-term antidepressant efficacy of adjunctive low-dose acetylsalicylic acid (ASA; 150 mg/day) over 2 months and its longer-term effect on relapse prevention over 12 months. Methods: ASPIRIN BD (EudraCT 2021-006635-25) was a multicentre, randomised, double-blind, placebo-controlled phase II trial at four Polish centres. Adults aged 18–60 years with a current bipolar depressive episode were randomised 1:1 to ASA or placebo for 12 months. The primary endpoint was the change in HAMD-17 score after 2 months, while the longer-term effect of ASA on relapse or clinical worsening was assessed over 12 months. Results: One hundred participants were randomised (50 per group). At month 2, ASA reduced HAMD-17 scores versus placebo (adjusted difference −4.24; 95% CI −7.20 to −1.28; p = 0.005; d = −0.51). Relapse or clinical worsening was less frequent with ASA (p = 0.026; NNT = 5). Depressive and bipolar remission rates were higher with ASA at month 6 (both p ≤ 0.003). Safety outcomes and adherence were comparable between groups. Conclusions: Adjunctive ASA 150 mg/day improved short-term depressive symptoms and reduced relapse or clinical worsening during a 12-month treatment period, with no clear safety signal. These findings warrant phase III confirmation.