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Re: We need placebo » SLS

Posted by Kon on August 2, 2005, at 0:25:39

In reply to Re: We need placebo, posted by SLS on July 30, 2005, at 10:19:03

>When one includes only a population of depressives rated as severe, the placebo response approaches zero while the response rate remains at 65-70%.

Just to add to the dunno category...this argument has been questioned in the recent July 16, 2005 BMJ:

http://www.freerepublic.com/focus/f-chat/1445096/posts

The authors write:

"A key claim in the NICE guideline is that the superiority of antidepressants over placebo correlates positively with the severity of depression being treated. This belief is an old one. In 1958 Kuhn suggested that endogenous depression was more responsive to antidepressants than neurotic or reactive depression, which was generally regarded as less severe.7 Regression to the mean may account for this impression since it entails that people with more severe depression at baseline will show greatest overall levels of improvement. But it does not explain drug-placebo differences, because greater improvement among patients with more severe depression occurs regardless of whether they are treated with a drug or placebo.
An early review of controlled trials found that evidence about whether endogenous symptoms predicted response was inconsistent.8 Recent evidence comes from post-hoc analysis in trials with otherwise negative resultsw6 w7 and from meta-analyses. The meta-analysis by Angst et al is often cited in support of the severity hypothesis, but severity effects were weak and mostly non-significant.9 Effects in another meta-analysis were more impressive, but data were provided only for investigational antidepressants and not established ones, where the evidence seemed to be weaker.10 In contrast, another recent meta-analysis found no relation between severity and antidepressant effect,11 and a meta-analysis of older studies showed that differences between antidepressants and placebo were smaller and non-significant in inpatient trials compared with outpatient trials.12 The NICE meta-analysis failed to find a consistent gradient of effect from "moderate" (Hamilton score 14-18) through "severe" (19-22) to "very severe" depression ( 23).1 In fact, the middle group, which would generally be referred to as moderately depressed, tended to show larger effects than either of the other two, but numbers of studies were small.
Thus there seems to be little support for the suggestion that recent failure to find marked differences between antidepressants and placebo is due to recruitment of patients with mild depression that is less responsive to antidepressants.1 Indeed, in the meta-analysis by Kirsch et al, all but one of the trials were conducted in patients with severe to very severe depression according to NICE criteria.6 The possibility that patients in the mid-range of severity show a greater antidepressant response, as suggested by the NICE data and by Joyce and Paykel,8 would not be expected from a simple biological effect. It may indicate that this group is more susceptible to some methodological artefact such as infringement of the double blind (see below)."



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poster:Kon thread:534296
URL: http://www.dr-bob.org/babble/20050728/msgs/536602.html