TY - JOUR T1 - Which first-line antidepressant? JF - British Journal of General Practice JO - Br J Gen Pract SP - 114 LP - 115 DO - 10.3399/bjgp19X701405 VL - 69 IS - 680 AU - Tony Kendrick AU - David Taylor AU - Chris F Johnson Y1 - 2019/03/01 UR - http://bjgp.org/content/69/680/114.abstract N2 - Choice of first-line antidepressants for depression has been debated in psychiatric journals over the last 9 months, in relation to the widely reported meta-analysis by Cipriani et al in the Lancet, comparing 21 antidepressants for efficacy and tolerability.1 They found that agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants.1 They also found agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine to be relatively better tolerated than others.1 Three antidepressants with higher efficacy also had relatively high acceptability: agomelatine, escitalopram, and vortioxetine. So should these antidepressants now be considered first-line choices for depression in primary care?The Cipriani group’s conclusions should be treated with some caution, as they are based on network meta-analysis (NMA). NMA methodology enables multiple treatments to be compared using both direct comparisons within randomised controlled trials, and indirect comparisons across trials based on a common comparator. So, if antidepressants ‘A’ and ‘C’ have each been compared with antidepressant ‘B’ directly, you can infer how ‘A’ would perform compared with ‘C’ through NMA, even if ‘A’ and ‘C’ have never been compared in the same trial. However, the inferences from NMAs that some antidepressants are more effective or acceptable than others are not always consistent with direct head-to-head comparisons of drugs within trials. It is therefore important to look also at systematic reviews of trials comparing drugs with each other directly.This is not the first time Cipriani’s group has suggested that escitalopram should be a preferred first-line choice due to its combined higher efficacy and tolerability. In 2009, they published an NMA comparing 12 antidepressants showing similar clinically important differences in favour of escitalopram and sertraline.2 Following the 2009 study, sertraline prescribing rose significantly while citalopram prescribing levelled off, and that of fluoxetine fell.3 However, escitalopram … ER -