BackgroundFew randomised controlled trials (RCTs) have examined potential preventive agents in high-risk community populations.AimsTo determine whether a mental health literacy intervention, the promotion of physical activity, or folic acid plus vitamin B¹²reduce depression symptoms in community-dwelling older adults with elevated psychological distress.MethodAn RCT with a completely crossed 2 × 2 × 2 factorial design: (400 mcg/d folic acid + 100 mcg/d vitamin B¹²v.placebo)×(physical activityv.nutrition promotion control) × (mental health literacyv.pain information control). The initial target sample size was 2000; however, only 909 adults (60–74 years) met the study criteria. Interventions were delivered by mail with telephone calls. The main outcome was depressive symptoms on the Patient Health Questionnaire (PHQ–9) at 6 weeks, 6, 12 and 24 months. The Clinicaltrials.gov registration number is NCT00214682.ResultsThe drop-out rate was low (13.5%) from randomisation to 24-month assessment. Neither folic acid + B¹²(F(3,856) = 0.83,P= 0.476) nor physical activity (F(3,856) = 1.65,P= 0.177) reduced depressive symptoms at any time point. At 6 weeks, depressive symptoms were lower for the mental health literacy intervention compared with its control condition (t(895) = 2.04,P= 0.042).ConclusionsMental health literacy had a transient effect on depressive symptoms. Other than this, none of the interventions significantly reduced symptoms relative to their comparator at 6 weeks or subsequently. Neither folic acid plus B¹²nor physical activity were effective in reducing depressive symptoms.