A network meta-analysis of 115 trials ranked escitalopram, agomelatine and duloxetine above fluoxetine for keeping patients well, but experts stress the differences are modest and no one should switch medication without medical advice.
Escitalopram performed best at helping people with depression both recover and stay well, according to a large analysis published in The Lancet Psychiatry on 10 November 2026. The systematic review and network meta-analysis, led by researchers at Radboud University Medical Center (Radboudumc) in the Netherlands, compared 20 antidepressants with one another and with fluoxetine, widely known as Prozac, which served as the reference drug. According to Radboudumc, the team pooled results from 115 randomised clinical trials involving more than 30,000 participants. Agomelatine and duloxetine ranked next, and all three outperformed fluoxetine on sustained response, meaning patients improved and remained well rather than relapsing.
The researchers say the focus on longer-term outcomes matters because depression can return after recovery, and doctors already advise many patients to stay on antidepressants for at least six months after symptoms ease before tapering off gradually. Compared with fluoxetine, people taking escitalopram were more likely to improve and stay improved and less likely to stop their medication, while other drugs, including sertraline, were no better than fluoxetine, the BBC reported. "If you start an antidepressant, choose one that not only helps you to get well, but also keeps you well," said Professor Eric Ruhé of Radboudumc. First author Paul van Haaren noted that agomelatine works well but carries a risk of liver failure as a side effect.
Independent experts urged caution in interpreting the rankings. Dr Sameer Jauhar of Imperial College London said the research cannot tell which antidepressant will work best for an individual patient and should not prompt someone responding well to their current medicine to change treatment. Professor Allan Young of the Royal College of Psychiatrists said the differences between drugs are modest and unlikely to outweigh factors such as side effects, previous response and patient preference. The authors suggest the findings could inform future clinical guidelines, while experts say longer studies are still needed. Anyone taking antidepressants should discuss any change with a doctor rather than stopping or switching on their own.
