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March 19, 2018

Yes, antidepressants work. (But maybe not as well as you think.)

Daily Briefing

    A new study shows that published data may be biased toward studies that cast antidepressants in a positive light—and fuller data comprising of both published and unpublished studies shows that the drugs have "mostly modest" effects, Aaron Carrol writes for the New York Times' "The Upshot."

    The controversy around antidepressants

    The effectiveness of antidepressants has been "hotly debated" in recent years, Carroll writes. Skeptics have argued that the research supporting antidepressants suffers from publication bias: That is, studies that show a positive effect are more likely to be published than those that showed no effect.

    For instance, a 2008 meta-analysis examined 74 antidepressant trials with more than 12,500 patients registered to FDA to support marketing or labeling changes. The researchers found that antidepressants outperformed placebos in only half of the studies—and while nearly every study that showed the antidepressants in a positive light had been published, just three of the negative studies were published in negative way that made their negative findings clear. Meanwhile, 22 were never published, and 11 were published but re-contextualized so that they seemed to be positive.

    That meta-analysis, and other similar research, led critics to suggest that antidepressants could be far less effective than commonly believed. John Ioannidis of Stanford University School of Medicine made the case in the journal Philosophy, Ethics, and Humanities in Medicine in 2008, arguing that antidepressants in many studies achieved "statistical significance" without achieving "clinical significance," Carroll writes.

    A new study sheds light on antidepressants' effects

    To help resolve the controversy, a team of researchers, including Ioannidis, analyzed a broader set of data that included published and unpublished studies conducted up until 2016. Carroll writes that the researchers used a "network meta-analysis technique" that allowed them to compare multiple treatments "both within individual trials directly and across trials indirectly to a common comparator."

    After examining 522 trials that included more than 116,000 patients, the researchers found that all of the antidepressants studied were, in fact, more effective than placebos—though efficacy and acceptability varied between drugs. Further, the evidence demonstrated only that the drugs are effective in treating major depression in the short term. Their longer-term effectiveness, and their success in treating mild or moderate depression, remains unclear.

    The researchers also found that industry-sponsored and non-industry-sponsored studies produced similar results. However, Carroll notes, the vast majority of the trials they analyzed were industry-sponsored, so researchers may not have had enough evidence to determine whether a difference existed.

    What's next?

    "Because we lack good data," Carroll writes, "we still do not know how well antidepressants work for those with milder symptoms that fall short of major depression, especially if patients have been on the drugs for months or even years." He added that it's possible that the benefits some people receive from antidepressants are due to a placebo effect.

    Ioannidis in an interview with Carroll expressed hope that future studies will provide better guidance on how antidepressants can be used on an individual level. He also expressed concern about some media coverage of his latest research, Carroll writes.

    "I am afraid that some news stories gave very crude interpretations that may be misleading, especially when their titles were too absolute, like 'the drugs work', 'the debate is over' and so forth," Ioannidis told Carroll, adding, "The clinical (as opposed to statistical) significance of the treatment effects that we detected will continue to be contested, and it is still important to find ways that one can identify the specific patients who get the maximum benefit" (Carroll, New York Times, "The Upshot," 3/12).

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