(see below), which he believes would also reduce the true
effect size, and concludes that “the difference became
large enough to be clinically important only in the very
small minority of patient populations with severe major
depression.” He further claims that although antidepressants
appear to show better efficacy with increasing severity
of depression in some studies, he views this as
attributable to placebos having decreased efficacy, rather
than antidepressants being more effective by comparison.
Ioannidis argues that antidepressant have essentially
no efficacy because:
(Point 1) The drug companies suppress negative studies,
biasing the literature.
(Point 2) Drug-placebo differences are small, and
presumably vanish because of this suppressed evidence
and because of methodological imperfections
in clinical trials:
i) Studies have outcomes that are “non-relevant
outcomes”, too small an improvement to be
clinically relevant.
ii) Studies are too short.
iii) The statistics used to analyze data falsely
exaggerate drug-placebo differences.
iv) Using too many exclusion criteria might
inflate drug-placebo differences.
v) Placebo lead-in periods falsely inflate the
drug-placebo differences.
vi) The use of multiple active treatment groups
(several groups versus one placebo group) is
unethical and might reduce the drug-placebo
difference.
(Point 3) The drug-placebo difference is larger in the
more severely depressed subgroups and in the older
studies, which included more severely depressed
patients, so for the majority of patients the effect
size must be negligible.
(Point 4) Since the cause of depression is complex
and multifactorial with both biological and non-biological
etiology, you would not expect a large antidepressant
effect size.
(Point 5) Antidepressants have unknown risks.
(Point 6) Depression is over-medicalized and overtreated.
Ioannidis sometimes phrases his conclusions as conditional
statements: “if most of the antidepressants efficacy
is simply the placebo effect....” or “these agents may be of
clinical use only in severely depressed people.” These and
other statements plus the title that antidepressant efficacy
is a myth all suggest that Ioannidis is asserting that antidepressants
do not help depressed patients at all except for
his hedge, that it may help “a very small minority.” He
then states some of the implications of this lack of efficacy.
(see below), which he believes would also reduce the trueeffect size, and concludes that “the difference becamelarge enough to be clinically important only in the verysmall minority of patient populations with severe majordepression.” He further claims that although antidepressantsappear to show better efficacy with increasing severityof depression in some studies, he views this asattributable to placebos having decreased efficacy, ratherthan antidepressants being more effective by comparison.Ioannidis argues that antidepressant have essentiallyno efficacy because:(Point 1) The drug companies suppress negative studies,biasing the literature.(Point 2) Drug-placebo differences are small, andpresumably vanish because of this suppressed evidenceand because of methodological imperfectionsin clinical trials:i) Studies have outcomes that are “non-relevantoutcomes”, too small an improvement to beclinically relevant.ii) Studies are too short.iii) The statistics used to analyze data falselyexaggerate drug-placebo differences.iv) Using too many exclusion criteria mightinflate drug-placebo differences.v) Placebo lead-in periods falsely inflate thedrug-placebo differences.vi) The use of multiple active treatment groups(several groups versus one placebo group) isunethical and might reduce the drug-placebodifference.(Point 3) The drug-placebo difference is larger in themore severely depressed subgroups and in the olderstudies, which included more severely depressedpatients, so for the majority of patients the effectsize must be negligible.(Point 4) Since the cause of depression is complexand multifactorial with both biological and non-biologicaletiology, you would not expect a large antidepressanteffect size.(Point 5) Antidepressants have unknown risks.(Point 6) Depression is over-medicalized and overtreated.Ioannidis sometimes phrases his conclusions as conditionalstatements: “if most of the antidepressants efficacyis simply the placebo effect....” or “these agents may be ofclinical use only in severely depressed people.” These andother statements plus the title that antidepressant efficacyis a myth all suggest that Ioannidis is asserting that antidepressantsdo not help depressed patients at all except forhis hedge, that it may help “a very small minority.” Hethen states some of the implications of this lack of efficacy.
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