Meet the Big 21 from the Largest Ever Study on Antidepressants – Mechanisms of Actions, Side effects and Indications
The recent Cipriani et al. systematic review and network meta-analysis is the largest and most comprehensive examination of antidepressant efficacy and tolerability. The network meta-analysis (NMA) covered an extensive list of 21 antidepressants and placebo which included a total of 116477 patients in 522 double-blind, parallel RCT’s. 
This article aims to provide a reader with a summary of the antidepressants featured in the NMA that should help with the individualised choice of antidepressant therapy by taking into account clinical features and tolerability.
The antidepressants have been divided into first and second line based on the recent RANZCP guidelines. 
It is important to recognise that according to the guidelines there is some flexibility regarding 1st, 2nd, and 3rd treatment, based on patient’s symptoms. e.g Duloxetine may be a 1st line in a patient with depression and pain. SNRIs have been positioned as the 2nd line only because of more significant toxicity in overdose.
SNRIs and TCAs are more effective than SSRIs in treating severe depressive symptoms (HAM-D > 25) and melancholic depression and hence may be prescribed first line in these situations.
The antidepressants have been arranged in alphabetical order.