Discontination of Antidepressants in Remitted Depression

Overprescribing and long-term use of antidepressants (ADs) are common and may increase the risk of adverse effects and withdrawal symptoms when discontinuation is attempted. Although several discontinuation strategies have been proposed, empirical evidence comparing different tapering approaches is limited. In particular, hyperbolic tapering has been suggested as a potentially safer and more effective alternative to standard linear tapering, but no randomized trials have directly compared these strategies.

This study is a pragmatic, multicentre, open-label, parallel-group, superiority randomized trial designed to compare two antidepressant discontinuation strategies-linear tapering and hyperbolic tapering-in adults with remitted depressive disorders. Eligible participants are adults aged 18 years or older with currently remitted depressive disorders who have been taking antidepressants for at least six months and are considered clinically appropriate candidates for discontinuation.

Participants will be recruited in outpatient psychiatric settings, with the involvement of general practitioners and other medical specialists. After baseline assessment, participants will be randomized to either a linear tapering strategy, consisting of dose reductions of 50% of the minimal effective dose every two weeks until discontinuation, or a hyperbolic tapering strategy, consisting of proportional dose reductions of approximately 20-25% every two weeks until discontinuation. Follow-up assessments will be conducted regularly over a 36-week period.

The primary outcome is the proportion of participants who fail to discontinue the antidepressant within the predefined tapering schedule (allowing a limited tolerance period) or who re-initiate antidepressant treatment during the 16 weeks following discontinuation. Secondary outcomes include measures of safety, tolerability, acceptability, clinical effectiveness, and cost-effectiveness, as well as withdrawal symptoms, relapse of depressive or anxiety symptoms, and adherence to the tapering schedule.

Participants and recruiting clinicians will not be blinded to treatment allocation, while outcome assessors and the biostatistician will remain blinded until completion of the study to minimize detection bias. The study aims to provide pragmatic evidence to inform clinical practice and guideline development regarding optimal strategies for antidepressant discontinuation.