Redressing long-term antidepressant use (RELEASE): Pragmatic cluster randomised controlled trial in general practice

BACKGROUND Safe and effective antidepressant deprescribing strategies are needed in general practice where most antidepressant prescribing occurs. METHODS We conducted a pragmatic, cluster-randomised controlled trial in general practice to test invitation to general practitioner (GP) review combined with resources to inform shared decision-making and guide hyperbolic tapering for stopping antidepressants compared to usual care. Adults taking antidepressants for longer than 12 months were recruited from 26 Australian GP practices between March 2023 and November 2024, irrespective of their intention to stop or depression or anxiety symptom scores. The primary outcome was cessation at 12 months. Secondary outcomes included cessation at 6 months, and >75% dose reduction and depression, anxiety and withdrawal symptom scores at 6 and 12 months. RESULTS Overall, 483 patients were randomised. Mean age was 50 years; 73% were women; mean duration of antidepressant use was 14.1 years. Cessation at 12 months was observed in 32 of 215 (14.9%) intervention and 16 of 187 (8.6%) usual care patients (odds ratio (OR) = 1.95 [95%CI, 1.00 to 3.81]; p=0.050). Cessation at 6 months was observed in 11.7% intervention vs 4.8% usual care (OR = 2.68; 95%CI, 1.18 to 6.05), and >75% dose reduction at 12 months in 19.6% intervention vs 9.9% usual care (OR = 2.28; 95%CI, 1.20 to 4.31). Symptom scores were similar between groups. No adverse events were attributable to the intervention. CONCLUSIONS In general practice, invitation to GP antidepressant review combined with information and guidance on hyperbolic tapering can support cessation or dose reduction without causing adverse effects or relapse. Absolute cessation rates were modest but still meaningful given the high prevalence of long term antidepressant use. TRIAL REGISTRATION ANZCT registry identifier, ACTRN12622001379707p.