lasting a month (the effect of treating an episode), resulting
in a total of 5 months lifetime depression. This example,
of course, implicates that the antidepressant effect
does not fade away over the years.
Ioannidis’ Criticism of Antidepressant Trials
Ioannidis labels the effect size he reported as small, and
we will not argue about the label, “small”. We present
data in Tables 1 and 2 based on a range of studies of
the most widely used antidepressants. This includes
hundreds of placebo-controlled randomize doubleblinded
trials (the best controlled of studies in the evidence
hierarchy), conducted throughout the world, by
scientists in industry as well as in academic settings, but
we cannot cover all of Ioannidis’s 1000 randomized controlled
trials. The efficacy is consistent with pragmatic,
epidemiological, service research and clinical research.
Note the agreement between the studies Ioannidis
quotes and ours for the newer studies, as summarized
in Tables 1 and 2. His argument is that the effect size
would be reduced to essentially zero (i.e. antidepressants
are not materially superior to placebo since the data is
based on biases from the suppression of negative studies
by industry and smaller still if you counted in negative
unpublished studies); and the 6 biases, which would
surely decrease it further. We question the logic of Ioannidis’
assertion that industry bias could reduce efficacy
to zero. To do so, there would have to be an equal
number of studies showing drug worse than placebo,
and Ioannidis fails to show any evidence that this is the
case. He starts with an effect size of 0.31 and assumes
suppression of negative studies would reduce it still
more, but his effect size of 0.31 is based on all studies
in this FDA report-not just published study. As industry
is required by law to report all studies to FDA for registration,
this is another reason to doubt his premise.
Ioannidis states, and we agree, that current evidence
suggests that more severely depressed patients show a
larger absolute degree of improvement relative to placebo
controls than do more mildly depressed patients
and symptomatic volunteers [35-38], but does not report
the effect size in the moderately and severely depressed