patients. He criticizes the use of exclusion factors, which
does reduce the ability to generalize to a broader range
of patients, but the exclusion of serious hospitalized
depressed or suicidal patients would reduce the generalization
to the patients who need and benefit from antidepressants
the most. As a result, the effect size of
antidepressant might be greater than reported.
Ioannidis also makes a few technical methodological
criticisms of clinical trials, which would apply to trials of
medical drugs as well, and we agree that these are problem
areas for all drugs. We agree with Ioannidis when
he notes that drug-placebo difference has decreased in
recent years [26,27]. Some of the reasons for this are:
(a) More recent studies exclude suicidal, and the
hospitalized more severe depressions, which have a
larger drug-placebo difference, but the exact comparison
of effect size should not be made due to
methodological differences between earlier and more
recent trials;
(b) Many of those with low baseline rating scores do
not have the type of depression helped by drugs;
(c) Patients who were helped by drugs in the past no
longer volunteer for placebo controlled trials;
(d) The more recent trials are not depressed patients
of a physician seeking consultation, but rather symptomatic
volunteers who answer an ad for a clinical
trial, done by the clinical trial companies (working
on a contract with pharmaceutical companies) and
are paid per case;
(e) The clinical trial companies have difficulty finding
patients, and may inflate the baseline rating to
ensure that the patient is enrolled in the study,
introducing a false improvement in both drug and
placebo (baseline inflation has been well documented
in recent studies [39-41]);
(f) Volunteers may collect their payment, but not
actually take their pills, further reducing drugplacebo
differences;
We question his generalization and interpretation of
the data to virtually all depressed patients based on data