Strategic Use of New generation antidepressants for Depression - SUN(^_^)D

Between December 2010 and March 2015, we recruited 2,011 participants with hitherto untreated major depression at 48 clinics in Japan. In Step 1, 970 participants were allocated to the 50 mg/day and 1,041 to the 100 mg/day arms; 1,927 (95.8%) provided primary outcomes. There was no statistically significant difference in the adjusted PHQ-9 score at week 9 between the 50 mg/day arm and the 100 mg/day arm (0.25 points 95% CI, -0.58 to 1.07, P=0.55). Other outcomes proved similar in the two groups. In Step 2, 1,646 participants not remitted by week 3 were randomised to continue sertraline (n=551), to add mirtazapine (n=537), or to switch to mirtazapine (n=558): 1,613 (98.0%) provided primary outcomes. At week 9, adding mirtazapine achieved a reduction in PHQ-9 scores of 0.99 points (0.43 to 1.55, P=0.0012); switching achieved a reduction of 1.01 points (0.46 to 1.56, P=0.0012), both relative to continuing sertraline. Combination increased the percentage of remission by 12.4% (6.1% to 19.0%) and switching by 8.4% (2.5% to 14.8%). There were no differences in adverse effects.