RATIONALE: In the Netherlands, >1 million individuals use antidepressants (ADs). The majority of patients discontinue their AD at some point, but around 30-55% experience problems like withdrawal symptoms and are unable to successfully discontinue. This particularly occurs with the com¬monly used ADs paroxetine (PAR) and venlafaxine (VLX). One major question is whether the method of AD discontinuation determines the chances of success that patients can discontinue their AD.
RESEARCH QUESTION: Is AD discontinuation more successful with gradual tapering of AD dosages (with progressively smaller dosage-units) or conventional 2-step reduction (available dosage-units, currently treatment as usual)?
STUDY DESIGN: Multicenter double-blind randomized (1:1) controlled trial of 200 patients with remitted depression using PAR (20-50mg) or VLX (75-375mg).
TAPER-AD has three consecutive phases (52 wks):
Phase I: Non-contrasting double-blind phase for dosages higher than the minimal effective dose (MED; PAR, 20mg; VLX, 75mg): dose reduction in steps of 10/75mg per 2 weeks until MED (max. 8 wks).
Phase II: Contrasting double-blind phase; i) conventional dose reduction (using available dosing-units) vs. ii) gradual dose reduction from the MED (max. 10 wks).
Phase III: Follow up without medication (max. 38 wks)
All participants complete a 2-week verum run-in and a 4-week placebo run-out period.
OUTCOMES: Primary outcome is the rate of failure to successfully discontinue an AD defined as significant deviation from the discontinuation protocol (e.g. additional AD use or stopping study medication) and/or significant withdrawal symptoms (high withdrawal symptoms during at least two consecutive assessments) in Phase II. Secondary outcomes are withdrawal symptom severity, depressive symptoms, recurrence rate and time to recurrence, daily functioning, and quality of life. Cost effectiveness is evaluated from a societal perspective, and determinants of discontinuation success are examined.