Antidepressants Differ in Efficacy and Acceptability in Long-Term Treatment of Major Depressive Disorder

Escitalopram, duloxetine, and agomelatine achieved higher sustained response rates than fluoxetine, while escitalopram and duloxetine also showed lower all-cause discontinuation, according to a systematic review and network meta-analysis of 115 double-blind randomised controlled trials (30,428 participants) comparing 21 antidepressants for long-term (>12 weeks) treatment of adult unipolar major depressive disorder. In the primary analysis of head-to-head continuation and continuation–extension studies (35 studies; n=9,888), escitalopram (OR 1·62), duloxetine (OR 1·57), and agomelatine (OR 1·40) showed higher sustained response rates than fluoxetine, whereas bupropion and reboxetine showed lower sustained response rates against four other antidepressants. For acceptability, escitalopram (OR 0·60) and duloxetine (OR 0·64) demonstrated lower all-cause discontinuation compared with fluoxetine, while reboxetine and milnacipran showed higher all-cause discontinuation against six and four other antidepressants, respectively; sensitivity analyses incorporating enrichment-design studies corroborated these results, though the certainty of evidence and the high risk of bias in 19 of 35 studies may limit reliability. These findings can inform shared decision making for patients, prescribers, and carers in real-world practice, while more head-to-head comparative studies are needed to provide reliable information about long-term effects of all licensed antidepressants. Source: https://www.thelancet.com/