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The efficacy of antidepressants: A Q&A with John Ioannidis

In a meta-analysis of more than 500 clinical trials, researchers have new conclusions about the efficacy of 21 different antidepressants.

There's a wide debate surrounding the use of antidepressants. Do they really work? If so, how well? And how do you know which one to select?

In a giant meta-analysis of 522 randomized clinical trials, an international team of researchers set out to better understand antidepressant efficacy and reliability. Results of their deep-dive analysis showed that each of the 21 drugs in this study were more effective at treating depression compared to a placebo — although not wildly successful. That conclusion may not seem like a big deal, but it's an affirmation of the validity of using pharmacological tools to help alleviate depression.

John Ioannidis, MD, DSc, co-director of the Meta-Research Innovation Center at Stanford and author on the paper, which published in journal The Lancet, recently talked with me about the meta-analysis. Here's a glimpse of our exchange:

What new light does this study shine on antidepressant treatment and antidepressants generally?

...By putting together cleaned, standardized data from more than 116,000 patients and 522 randomized trials, and by using the highest possible standards of analysis, we can offer some concrete evidence to inform the proper use of 21 different antidepressants.

What would you say are the biggest takeaways of this analysis from the perspective of a clinician? What about from the perspective of a patient with depression?

...All 21 antidepressants that we assessed are better at treating depression than placebo, although the benefit is, on average, quite modest...

Finally, different agents have different profiles of efficacy and acceptability. Our study shows the relative merits and harms of each of the 21 antidepressants compared against one another. Some of them seem to be better, or more acceptable, although the differences between them are less pronounced when we compare them against placebo.

A patient can discuss this information with his or her physician and make a choice to start a specific antidepressant, if it is indicated, with some particular evidence-based expectations in mind. Of course, different patients may still respond differently, and this is difficult to predict ahead of time. But at least there is sensible and congruent information that informs patients on the average response that he or she can expect to have if taking one of these antidepressants.

Do you think the results of this study carry implications for drug developers?

Our analysis clearly shows that there is a lot of room for improvement — both in efficacy and in acceptability compared with the currently available treatments. Thus, focusing on developing new drugs would be welcome and our analysis can provide a yardstick of what the currently available drugs can achieve for comparison. It also shows that differences between available drugs are modest, therefore new research is needed to find drugs that use very different modes of action and may thus achieve better results.

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