Twenty-six RCTs (11,115 participants) were included in the review. Sample sizes ranged from 45 to 1,801 patients. Randomisation was adequately reported in 17 RCTs. Eighteen trials clearly reported blinding of outcome assessors. There was at least 80% follow-up in 19 RCTs. Seventeen studies reported sample size calculations.
None of the five studies of interventions with an educational focus reported improvements in educational adherence compliance or persistence. Two studies found improvements in treatment response and mental health status at six-months follow-up. One study used a behaviour-focused intervention that resulted in improvements in medication compliance and depressive symptoms.
Twenty studies evaluated 22 multifaceted interventions. Eleven interventions showed significantly positive effects on adherence outcomes and depression outcomes compared to usual care. Four interventions reported positive effects for medication adherence only and four interventions improved depression outcomes without improving adherence. There were no improvements in either adherence or depression outcomes reported for three interventions. All seven interventions that used pharmacy refill monitoring reported improvements in adherence to medication. Benefits in adherence and depression outcomes were observed in two trials of patients with major depression and in two further trials of patients with difficult-to-treat depression with interventions that consisted of collaborative care between primary care physicians and the mental health specialty sector. Intensive depression care programmes were found to improve adherence and clinical outcomes in two studies. Two of five trials that utilised telephone-based care management found benefits in adherence and clinical outcomes.