A review of 522 trials published between 1979 and 2016, covering 116,477 patients total, found that common antidepressants really do work. Some are more effective than others, but all were more effective than a placebo, and even a placebo was better than nothing.

Image credits: Zahy1412 / Wikipedia.

They work… generally

Antidepressants are a controversial topic. They’ve been called everything from snake oil to a giant conspiracy to dumb us down, although they’ve been prescribed for decades and have been approved by the US Food and Drug Administration and similar regulatory agencies in other countries.

Unfortunately, the debate around antidepressants has been more ideological than scientific, but even at the scientific level, things are not entirely clear. This is where this new study steps in, attempting to draw conclusions about the overall efficiency of antidepressants. Lead researcher Dr. Andrea Cipriani, from the University of Oxford, told the BBC:

“This study is the final answer to a long-standing controversy about whether antidepressants work for depression. We found the most commonly prescribed antidepressants work for moderate to severe depression and I think this is very good news for patients and clinicians.”

His conclusions were echoed by the Royal College of Psychiatrists, which said the study “finally puts to bed the controversy on anti-depressants”.

Overall, the analysis found that 21 common antidepressants were at least somewhat effective. However, there was a big variability in how well they fared. Researchers found that they ranged from being a third more effective than a placebo to being more than twice as effective. Notably, the most famous antidepressant of them all, Prozac (currently out of patent and commonly known by its generic name, fluoxetine), was one of the least effective options, though it was best tolerated (fewest side effects). Fluvoxamine, reboxetine, and trazodone, were also among the least effective, while on the other hand, amitriptyline, mirtazapine, and venlafaxine were the best-performing drugs.

The importance of addressing depression cannot be overstated.

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“Depression is the single largest contributor to global disability that we have – a massive challenge for humankind,” said John Geddes, professor of epidemiological psychiatry at Oxford University. It affects around 350 million people worldwide and instances rose almost 20% from 2005-2015.

Image credits: whoismargot / Pixabay.

Controversy won’t end

However, this study is unlikely to end controversy and accusations of bias on either side and it won’t settle the debate. The fact that the conclusion “antidepressants work” was considered groundbreaking enough to be published in a reputable science journal says a lot about existing uncertainties in the field.

Researchers report that out of the 522 trials in the newly published meta-analysis, 409 were funded by pharma companies, but the risk of bias was considered low.

“Forty-six (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low,” note the authors.

Furthermore, several previous trials have cast serious doubts on antidepressants (at least some of them). For instance, in 2008, Irving Kirsch, associate director of the Program in Placebo Studies at Harvard Medical School published a meta-analysis showing antidepressants are no more effective than a placebo — but only when you also include unpublished trials. Through the Freedom of Information Act, the FDA demands pharmaceutical companies provide data on all the clinical trials they sponsor — including unpublished trials. Pharmaceutical companies have very little incentive to publish trials with negative results, and journals also almost never publish negative results, so published results are skewed towards positivity.

To make things even more complicated, different people have different problems and experience different results, that’s why we have more than one antidepressant in the first place. For instance, the effectiveness of antidepressants on teens and children has been proven time and time again to be much, much lower than on adults. Most drugs are barely effective if at all, which is something authors of this study admit.

“The present findings in adults contrast with the efficacy of antidepressants in children and adolescents, for which fluoxetine is probably the only antidepressant that might reduce depressive symptoms.”

There might be different mechanisms causing depression, potentially causing different types of depression, which is something that’s still a matter of active debate.

Lastly, this review only analyzed results over a period of 8 weeks. There have been studies which found that the effectiveness of antidepressants decreases over longer periods of time. However, this does nothing to diminish the merit of the study.

So the bottom line is, the largest ever review of antidepressants found that they do work, and on average, they’re always better than a placebo, over a period of 8 weeks. There are still significant voids in our understanding of depression, but this should ease the mind of both doctors administering and patients taking the antidepressants.

Journal Reference: Cipriani et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. DOI: https://doi.org/10.1016/S0140-6736(17)32802-7