Study identifies antidepressants that get patients well and keep them well First large-scale long-term comparison of medications for depression

Antidepressants not only alleviate depression symptoms in the short term, but also help sustain these benefits over the longer term. A new, major comparative study has found that three medications are the most effective in this regard. 'This helps doctors choose a medication that not only helps patients to get well, but also keeps them well.'

Worldwide, nearly six percent of people experience depression. Many of them continue taking antidepressants after achieving symptomatic improvement, amongst others to prevent a relapse of depression. An international team of researchers investigated whether and which antidepressants in particular can not only get the patients well but also keep them well (sustained response). This is the first large-scale study to compare different antidepressants over both short- and long-term use. Results have now been published in The Lancet Psychiatry.

This study utilized evidence from 115 previously conducted randomized clinical trials, involving more than 30,000 participants in total. Researchers compared 20 antidepressants with one another and with the best-known antidepressant, fluoxetine. Results suggested that antidepressants can indeed keep people well also during long-term use. Moreover, the study found evidence of differences between the various medications. These findings should inform the initial choice of antidepressants in view of their potential long-term use.

Guidelines

Three antidepressants were found to be more effective in the long term: escitalopram, agomelatine, and duloxetine. These medications performed better than fluoxetine. 'Escitalopram is already widely used', says first author Paul van Haaren. 'Agomelatine works well, but one of its side effects is the risk of liver failure. Duloxetine is less well known and is prescribed less frequently as a first-line treatment.'

Many international guidelines advise SSRIs as primary choice antidepressants. 'Of these SSRIs, escitalopram now appears to be the most effective, also for long-term use. This study may have implications for future treatment guidelines', says Eric Ruhé, Professor of Difficult to Treat Depression at Radboud university medical center.

Staying well

According to Ruhé, this does not mean that everyone with severe depression should now receive escitalopram. 'As a prescriber, you consider the balance between a medication’s benefits and side effects. That balance differs from person to person. Therefore, the choice of medication may vary for each individual patient. Nevertheless, our study can help inform the decisions that prescribers and patients make together: if you start an antidepressant, choose one that not only helps you to get well, but also keeps you well.'

If you have questions about your own antidepressant medication, please contact your treating physician.

About the publication

Researchers from Nijmegen, Amsterdam, Oxford, Kyoto, London, Osaka, and Bern contributed to this study. This research has been published in The Lancet Psychiatry: Comparative efficacy and   

acceptability of antidepressants in the long-term treatment of major depressive disorder: a systematic review and network meta-analysis. PCF van Haaren, JM van Gaalen, EG Ostinelli, K Shinohara, A Tajika, R Aronica, N Aoki, E Batista, S Ligthart, CH Vinkers, O Efthimiou, A Cipriani, TA Furukawa, HG Ruhé. DOI: https://doi.org/10.1016/S2215-0366(26)00326-3

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