A large-scale review of the most common antidepressants has found them all to be superior to placebo in treating major depression, potentially laying to rest questions over their effectiveness.

Researchers carried out a systematic review and network meta-analysis of data from placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults with major depressive disorder.

The data, published in The Lancet, showed that all antidepressants included in the study were more effective than placebo, but it also highlighted key differences between the drugs.

For one, the odds ratios (which measure the association between exposure and outcome) ranged from 2.13 for amitriptyline to 1.37 for reboxetine. With regard to tolerability, only agomelatine and fluoxetine were associated with fewer dropouts than placebo, while clomipramine was worse than placebo.

In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants, whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs, the researchers noted.

Agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants, whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates, they found.

"This study is the final answer to a long-standing controversy about whether anti-depressants work for depression,” lead researcher Dr Andrea Cipriani, from the University of Oxford, told BBC News.

"We found the most commonly prescribed anti-depressants work for moderate to severe depression and I think this is very good news for patients and clinicians."

“This rigorous study confirms that antidepressants have an important place in the treatment of depression,” Dr James Warner, Reader in Psychiatry, Imperial College London. “Depression causes misery to countless thousands every year and this study adds to the existing evidence that effective treatments are available.”

The study also “adds clarity about how effective and how well tolerated all the common antidepressants are, and should help clinicians and patients in treatment choices.”