Combining antidepressants better than monotherapy for some

Goodfellow Gems Logo

Goodfellow Gems

Combining antidepressants better than monotherapy for some

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.


  1. Combining Antidepressants vs Antidepressant Monotherapy for Treatment of Patients With Acute Depression: A Systematic Review and Meta-analysis JAMA Psychiatry (2022) View here

Gems are chosen by the Goodfellow director Dr. Bruce Arroll to be either practice changing or practice maintaining. The information is educational and not clinical advice.

As published in: