Walker, JanineMackinnon, AndrewBatterham, PhilipJorm, Anthony FHickie, Ian BJenkins (previously McCarthy), AffricaFenech, MichaelChristensen, Helen2015-12-082015-12-080007-1250http://hdl.handle.net/1885/34149Background: Few randomised controlled trials (RCTs) have examined potential preventive agents in high-risk community populations. Aims: To determine whether a mental health literacy intervention, the promotion of physical activity, or folic acid plus vitamin B12 reduce depression symptoms in community-dwelling older adults with elevated psychological distress. Method: An RCT with a completely crossed 2x2x2 factorial design: (400 mcg/d folic acid + 100 mcg/d vitamin B12 v. placebo)x(physical activity v. nutrition promotion control)x(mental health literacy v. 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. Results: The 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). Conclusions: Mental 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 B12 nor physical activity were effective in reducing depressive symptoms.Keywords: cyanocobalamin; folic acid; placebo; absence of side effects; adult; aged; article; clinical trial; controlled clinical trial; controlled study; depression; distress syndrome; drug safety; female; health survey; human; male; medical information; mental he201010.1192/bjp.bp.109.0752912016-02-24