No advantage was found for titrating sertraline to 100 mg compared with 50 mg for patients starting treatment for new onset depression; however, patients who did not respond to treatment by 3 weeks on antidepressants and were either switched to mirtazapine or given mirtazapine in addition to sertraline, did benefit from a small reduction in symptoms by week 9, according to a study published in BMC Medicine.

The Strategic Use of New generation antidepressants for Depression trial, which was open-label, multicenter, assessor-blinded, randomized, and controlled, sought to test the relative merits of the current guidelines for treating new onset depression: titrating antidepressants to the maximum range, if tolerated, then adding or switching if remission is not achieved after several weeks. Step 1 of the study randomly assigned patients to titration up to 50 mg of sertraline or 100 mg of sertraline. Patients who did not achieve remission after 3 weeks of treatment were randomly assigned to either continue sertraline, switch to mirtazapine, or add mirtazapine to the current dosage of sertraline as step 2 of the study. The primary outcome of depression severity was measured using the Patient Health Quesitonnare-9 (PHQ-9), which scores on a scale from 0 to 27, with 0 indicating no depression and 27 indicating severe depression.

At 48 clinics in Japan, 2011 participants with new onset, as yet untreated depression were recruited into the study between December 2010 and March 2015. For step 1, 970 patients were titrated up to 50 mg and 1041 up to 100 mg. At week 9, there was no statistically significant difference found between the adjusted PHQ-9 scores of the 50 mg group and the 100 mg group (0.25, 95.0% CI, -0.58 to 1.07, P =.55).

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For step 2, 551 of the 1646 patients who did not achieve remission by week 3 were randomly assigned to continue sertraline, 558 to switch to mirtazapine, and 537 to add mirtazapine to their current dosage of sertraline. At week 9, switching antidepressants achieved a 1.01 reduction in PHQ-9 scores relative to continuing sertraline (95% CI, -1.56 to -0.4, P =.0012), while adding mirtazapine achieved a 0.99 reduction in scores relative to continuing sertraline (95% CI, -1.55 to -0.43, P =.0012). 

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Switching increased remission rates by 8.4% , and combination treatment increased remission rates by 12.4%. There were no differences in adverse effects experienced in any group.

Study investigators conclude that “those who place a high value in treatments that have been tested in large trials that both minimize risk of bias and mimic real-world conditions may prefer the specific strategies used in this trial.”


Kato T, Furukawa TA, Mantani A, et al. 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. BMC Med. 2018;16(1):103.

This article originally appeared on Psychiatry Advisor