Debate over the efficacy of antidepressants has raged for years with a torrent of studies, often quite convincingly, arguing that the drugs are no better than a placebo, and research pointing to the contrary inevitably stained by pharmaceutical company bias. A new meta-analysis of over 500 trials covering the largest dataset evaluated to date has concluded that antidepressants are definitely more effective than a placebo.

The new study from the University of Oxford collected data from 522 trials encompassing a total of over 116,000 participants. To minimize bias in the data the study's authors contacted pharmaceutical companies and individual researchers to include a vast array of unpublished data in the calculations. Twenty-one commonly-used antidepressants were included in the study and while the results suggested all antidepressants were more effective than a placebo, some drugs were much more effective than others.

The antidepressants displaying the most effective results were agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine, while the least effective drugs were fluoxetine, fluvoxamine, reboxetine, and trazodone.

"By bringing together published and unpublished data from over 500 double blind randomized controlled trials, this study represents the best currently available evidence base to guide the choice of pharmacological treatment for adults with acute depression," says co-author Professor John Ioannidis. "The large amount of data allowed more conclusive inferences and gave the opportunity also to explore potential biases."

Of course, this study doesn't establish antidepressants as necessarily effective from any perspective other than compared to placebo. Andrea Cipriani, lead author on the study, does note that these drugs are still generally ineffective in about one third of patients so, "it's clear there is still a need to improve treatments further."

The response to this significant piece of research from other experts in the field has been positive. James Warner, from Imperial College London described the study as "rigorous", while Anthony Cleare from King's College London calls it an "important piece of work" that "puts to bed the idea that antidepressants don't work."

No study is absolute or definitive though, and while this cannot objectively tell us that antidepressants will work for everyone, the scale of the research does at the very least suggest that several of the major drugs analyzed do offer general success rates higher than placebos. Any further conclusions begin to push the limitations of the study as no detail in terms of efficacy related to age, sex or symptom severity could be analyzed.

This research hopefully removes any stigma associated with the use of antidepressants and indicates to patients that these drugs can actually be clinically valuable in some circumstances.

"Antidepressants can be an effective tool to treat major depression," adds Cipriani, "but this does not necessarily mean that antidepressants should always be the first line of treatment. Medication should always be considered alongside other options, such as psychological therapies, where these are available."

The study was published in the journal The Lancet.