drug-placebo difference has decreased in recent years
[26,27]. He supports this assertion, quoting Barbui [28],
concluding that “there is “absolutely” no difference
between paroxetine and placebo,” but this study actually
reported significant efficacy, finding that 52% of drug-treated
patients improved compared to 40% of placebo
patients, a typical finding more characteristic of recent studies
of mild depression and symptomatic volunteers.
Barbui was referring to all-cause discontinuation, an outcome
which does not measure efficacy per se, but rather
an outcome more of a measure of side effects than of efficacy.
The similar all-cause discontinuation rates found in
this study reflects that dropout due to medication side
effects is about equal to dropouts from placebo due to
poor efficacy. The older studies have greater effect sizes
than the newer studies and included more moderately and
severely ill patients. Due to changes in defining symptom
severity over the years, “mild” or “severe” are relative
terms, and a mildly ill patient in an earlier study might be
considered a severely ill patient in a more recent study.
There are, therefore, many differences between early and
later studies. We make no claim that any meta-analysis
reflects the true size effect of antidepressants. Our argument
is that a low effect size estimate is clinically significant
to some patients, and that the effect size, the
percentage difference of drug and placebo, is not zero.
Prevention of Future Episodes
An important antidepressant effect is the prevention of
future episodes in people with recurrent episodes. The
first author found (in the first meta-analysis done in psychiatry)
that antidepressants prevent relapses, in that 53%
of the placebo patients relapsed, whereas only 27% of
drug-treated patients relapsed [29], showing that drugs