Abstract
We reply to the Ioannidis’s paper “Effectiveness of antidepressants; an evidence based myth constructed from a
thousand controlled trials.” We disagree that antidepressants have no greater efficacy than placebo. We present the
efficacy from hundreds of trials in terms of the percentage of patients with a substantial clinical response (a 50%
improvement or more symptomatic reduction). This meta-analysis finds that 42-70% of depressed patients improve
with drug and 21%-39% improve with placebo. The response benefit of antidepressant treatment is 33%-11%
greater than placebo. Ioannidis argues that it would be vanishingly smaller because systematic biasing in these
clinical trials would reduce the drug-placebo difference to zero. Ioannidis’ argument that antidepressants have no
benefit is eroded by his failures of logic because he does not present any evidence that there are a large number
of studies where placebo is substantially more effective than drug. (To reduce to zero, one would also have to
show that some of the unpublished studies find placebo better than drug and have substantial systematic or
methodological bias). We also present the empirical evidence showing that these methodological concerns
generally have the opposite effect of what Ioannidis argues, supporting our contention that the measured efficacy
of antidepressants likely underestimates true efficacy.
Our most important criticism is Ioannidis’ basic underlying argument about antidepressants that if the existing
evidence is imperfect and methods can be criticized, then this proves that antidepressant are not efficacious. He
presents no credible evidence that antidepressants have zero effect size. Valid arguments can point out difficulties
with the data but do not prove that a given drug had no efficacy. Indeed better evidence might prove it was
more efficacious that originally found.
We find no empirical or ethical reason why psychiatrists should not try to help depressed patients with drugs and/
or with psychotherapeutic/behavioral treatments given evidence of efficacy even though our treatment knowledge
has limitations. The immense suffering of patients with major depression leads to ethical, moral, professional and
legal obligations to treat patients with the best available tools at our disposal, while diligently and actively
monitoring for adverse effects and actively revising treatment components as necessary.
AbstractWe reply to the Ioannidis’s paper “Effectiveness of antidepressants; an evidence based myth constructed from athousand controlled trials.” We disagree that antidepressants have no greater efficacy than placebo. We present theefficacy from hundreds of trials in terms of the percentage of patients with a substantial clinical response (a 50%improvement or more symptomatic reduction). This meta-analysis finds that 42-70% of depressed patients improvewith drug and 21%-39% improve with placebo. The response benefit of antidepressant treatment is 33%-11%greater than placebo. Ioannidis argues that it would be vanishingly smaller because systematic biasing in theseclinical trials would reduce the drug-placebo difference to zero. Ioannidis’ argument that antidepressants have nobenefit is eroded by his failures of logic because he does not present any evidence that there are a large numberof studies where placebo is substantially more effective than drug. (To reduce to zero, one would also have toshow that some of the unpublished studies find placebo better than drug and have substantial systematic ormethodological bias). We also present the empirical evidence showing that these methodological concernsgenerally have the opposite effect of what Ioannidis argues, supporting our contention that the measured efficacyof antidepressants likely underestimates true efficacy.Our most important criticism is Ioannidis’ basic underlying argument about antidepressants that if the existingevidence is imperfect and methods can be criticized, then this proves that antidepressant are not efficacious. Hepresents no credible evidence that antidepressants have zero effect size. Valid arguments can point out difficultieswith the data but do not prove that a given drug had no efficacy. Indeed better evidence might prove it wasmore efficacious that originally found.We find no empirical or ethical reason why psychiatrists should not try to help depressed patients with drugs and/or with psychotherapeutic/behavioral treatments given evidence of efficacy even though our treatment knowledgehas limitations. The immense suffering of patients with major depression leads to ethical, moral, professional andlegal obligations to treat patients with the best available tools at our disposal, while diligently and activelymonitoring for adverse effects and actively revising treatment components as necessary.
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