Objective: To differentiate characteristics of a discontinuation syndrome from a recurrence of major depressive disorder in the context of a randomized trial.
Method: We performed a randomized clinical trial to compare the efficacy of sertraline versus placebo for the prevention of recurrent postpartum DSM-IV major depressive disorder. Women whose depression did not recur in the initial 17-week active treatment trial were followed through the taper phase (weeks 18-20). At week 17, 3 women assigned to placebo and 8 assigned to sertraline remained in the trial. Nine symptoms that characterize discontinuation syndrome were extracted from the 25-item Asberg Rating Scale for Side Effects (ASE) and assessed weekly during the taper phase. The 21-item Hamilton Rating Scale for Depression was used to evaluate depressive symptoms.
Results: In the taper phase, there were no significant differences between the sertraline- and placebo-treated women on the sum of the ASE-derived symptoms. Both groups had low levels of symptoms on the ASE during the weeks of taper. None of the 3 women assigned to placebo and 2 of the 8 women assigned to sertraline suffered a depressive recurrence within 6 weeks of the end of the study.
Conclusions: A gradual taper of sertraline (75 mg) over 3 weeks did not lead to discontinuation syndrome; however, the systematic dissection of symptoms resulted in our conclusion that the duration of preventive therapy should be extended to 26 weeks (about 6 months) in subsequent randomized trials, consistent with the treatment guidelines for a single episode of depression.