Optimising first- and second-line treatment strategies for untreated major depressive disorder — the SUN☺D study: a pragmatic, multi-centre, assessor-blinded randomised controlled trial

Abstract

On the basis of the results of prior evidence [5] and existing practices [6, 7], we chose sertraline as the drug to be tested. Since the available evidence suggests that there may be differences between different classes of antidepressants with respect to dose-response relationship [15], the first hypothesis pertains to the choice of the initial target dose of an SSRI, and of sertraline in particular, within its therapeutic range. 2. [...]in the recently updated network meta-analysis of 21 antidepressants, mirtazapine was the second most potent antidepressant after amitriptyline [29]; its less favourable acceptability profile renders it less suitable as first-line treatment, but when first-line treatment fails, mirtazapine represents a potentially appropriate second choice. [...]the open-label design may have created some undetected performance bias that may threaten the internal validity of both the step 1 and step 2 comparisons, such as differential administration of co-prescriptions or psychological support. Because Japan does not have a primary care system, patients with new onset depressive episodes usually consult office practice psychiatrists directly. [...]in many other countries, primary care doctors would see and begin treatment of most participants entered in SUN☺D. In comparison to many multi-centre trials, we were able to enrol a large proportion (2011 of 7895) of potentially eligible patients.