A major study has found that antidepressants do work, and are more effective than a placebo.
However, researchers stress that different pills vary in effectiveness - and that the treatment will not work for all patients.
Antidepressants are widely prescribed around the world, there has been considerable debate around their effectiveness.
In a large-scale meta-analysis, researchers looked at the results of a total of 522 trials (involving 116,477 people) of 21 antidepressants.
It found that all antidepressants studied were more effective than a placebo.
The authors of the study, which has been published in the Lancet journal, concludes: "These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants."
The study did, however, discover significant variations in the level of effectiveness and side effects caused by different pills.
Important new study by @And_Cipriani et al. @TheLancet provides evidence that #antidepressants are more efficacious than placebo in adults with major depressive disorder - a systematic review and network meta-analysis #depression https://t.co/AzqTsKO9TV pic.twitter.com/M1s2jsLjsb
— J Opacka (@jopackaj) February 22, 2018
Research lead Andrea Cipriani stressed that antidepressants will not work for all patients, and that antidepressants should not always be the first line of treatment - citing therapies as one possible alternative.
Prof Carmine Pariante, a spokesperson for the Royal College of Psychiatrists, said the study "finally puts to bed the controversy on antidepressants".
He observed: "Importantly, the paper analyses unpublished data held by pharmaceutical companies, and shows that the funding of studies by these companies does not influence the result, thus confirming that the clinical usefulness of these drugs is not affected by pharma-sponsored spin.
"Of course, these type of studies cannot look at individual differences, so cannot inform us about the specific personal characteristics that make an individual more likely to respond in general, or to respond to one medication rather than another one."
While uncertainty remains about the causes of clinical depression, it is believed that antidepressants partially work by increasing levels of chemicals known as neurotransmitters.
The World Health Organisation estimates that around 300 million people suffer from depression globally.