A review of thirty-nine RCTs where a second antidepressant was added to an initial antidepressant, compared with just the initial antidepressant.1 The analysis suggested a benefit when mirtazapine was added to SSRI, TCA or Venlafaxine type medications but not bupropion. The effect size for the combination was an SMD = 0.31 which is similar to that for monotherapy versus placebo.
There were no trials with a placebo arm but these findings suggest an additive effect. The dose of mirtazapine was from 7.5 mg to 45 mg/day.
The authors suggested a combination can be considered as first line in severe cases or for patients who are considered non-responders. The severity reference was puzzling as the benefit was consistent at all levels of baseline severity.