![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by ed_uk on November 18, 2004, at 15:54:39
What do you think of this?? I found it on the internet. It describes some, but not all of the methodological problems with studies of ADs.............
It is generally assumed that antidepressants have been clearly established as more effective than placebo in double-blind controlled research. Morris and Beck (1974) conducted a comprehensive literature review that revealed that tricyclic antidepressants were superior to a placebo in 63 of 91 controlled studies conducted between 1958 and 1972. Although this review would appear to support the efficacy of antidepressants, there may be some problems that diminish the strength of the results. For example, studies with negative results are much less likely to be published (Greenberg & Fisher, 1989). Also, most controlled drug studies use an inert placebo that may, in effect, unblind the studies because the clinician raters can determine who is receiving the active medication by determining who is having side effects (Hughes & Krahn, 1985; Margraf et al., 1991). This could be a serious flaw because most drug studies rely primarily on potentially biased clinician-rated measures (e.g., the HRSD and the GAS) rather than on patient-rated measures (e.g., the BDI). It has been shown, in an extensive meta-analysis (Lambert, Hatch, Kingston, & Edwards, 1986), that patient-rated measures show a significantly smaller effect size than clinician-rated measures (i.e., patient raters tend to see less improvement than clinician raters). Another concern is that most antidepressant drug studies use a "washout" phase during which all prospective participants are placed on placebo (Greenberg & Fisher, 1989). Those prospective participants who show improvement during the washout phase are eliminated from the pool of participants. This routine procedure very likely creates a bias against the placebo condition in such drug studies before they even start by eliminating those individuals who may be "placebo responders." Thus, the actual placebo response rate may be seriously underestimated in most antidepressant studies.
Using the same study pool reviewed by Morris and Beck (1974), Thomson (1982) reviewed 75 placebo-controlled double-blind studies of tricyclic antidepressants conducted between 1958 and 1972 that met somewhat stricter methodological criteria. Only 7 of these studies used an active placebo, and only 1 of the studies using an active placebo showed the antidepressant to have a superior outcome to the placebo. ***Note by Ed- an active placebo is a drug which is believed to be ineffective for the treatment of the condition in question (depression) but which mimics the side effects on the active drug ie. the antidepressant.***
Despite the excitement about the newer antidepressants such as fluoxetine, a recent meta-analysis of nine controlled fluoxetine outcome studies showed only a modest mean effect size of 0.39 in comparison with controls on patient-rated measures (Greenberg, Bornstein, Zborowski, Fisher, & Greenberg, 1994). This effect size is comparable but not larger than that obtained in previous meta-analyses of tricyclic antidepressants. Interestingly, both clinician and patient outcome ratings correlated significantly with the percentage of patients experiencing side effects, suggesting that side effects may unblind these studies and bias the outcome measures.
Fisher and Greenberg (1993) conducted a worldwide literature search for psychotropic drug studies that evaluated whether or not the double blind had been penetrated. Of the 26 reports they were able to locate, 23 (88%) indicated that both patients and physicians were able to differentiate who was receiving the drug or placebo at rates significantly better than chance. Another recent study showed that clinical evaluators' subjective ratings of treatment outcome were significantly different depending on whether the clinical evaluator had correctly guessed the patients' condition (Carroll, Rounsaville, & Nich, 1994). This is likely to be a problem for both psychotherapy and drug treatment conditions but is likely to especially affect drug–placebo comparisons as a result of the presence or absence of drug side effects.
A recent meta-analysis (Greenberg, Bornstein, Greenberg, & Fisher, 1992b) reviewed 22 controlled studies (N = 2,230) that compared a placebo (usually inert) with an "old" antidepressant and a "new" antidepressant. Even if the clinician rater were unblinded by side effects, he or she would have difficulty distinguishing which of the active medications the patient was receiving, in effect making these studies somewhat "blinder." Overall, the old antidepressants and the new antidepressants showed a small (average effect sizes of 0.25 and 0.31, respectively) advantage over placebo on clinician-rated measures. Considering that most studies with nonsignificant findings are not published, the authors speculated that this advantage may, in fact, have been negligible. Interestingly, when patient-rated outcome measures were used, the old antidepressants were not significantly more effective than the placebo and showed an effect size of only 0.06. The data suggested that the new antidepressants did not fare much better. These effect sizes were far smaller than the effect sizes, ranging from 0.44 to 0.79, that had emerged from the earlier meta-analyses of tricyclic antidepressants (Morris & Beck, 1974; Thomson, 1982). These data suggest that relying on clinician ratings alone could lead to significant biases whenever the blind is penetrated.
Posted by pseudonym on November 18, 2004, at 17:17:24
In reply to Demonstrating the efficacy of ADs, posted by ed_uk on November 18, 2004, at 15:54:39
In my opinion, all placebos should taste moderately bad. That way, you unconciously believe you're getting an active substance.
I've been through a number of clinical trials and I can tell you the double-blind is really closer to a single blind, where the one in the dark is the clinician or rater. The guinea pig (myself) knew whether or not it was an active substance by virtue primarily of taste, and second, by side effects.
That said, I think the LSAS is a good instrument for assessment of social anxiety.
Posted by SLS on November 18, 2004, at 17:37:43
In reply to Demonstrating the efficacy of ADs, posted by ed_uk on November 18, 2004, at 15:54:39
Hi Ed.
It would be interesting to work backwards.
We know that antidepressants work. If our current study designs fail to demonstrate this, then we have a problem with the way efficacy is investigated.
- Scott
Posted by ed_uk on November 19, 2004, at 9:09:38
In reply to Re: Demonstrating the efficacy of ADs » ed_uk, posted by SLS on November 18, 2004, at 17:37:43
We rely on double blind trials to demonstrate efficacy though!
Posted by SLS on November 19, 2004, at 10:26:54
In reply to Re: Demonstrating the efficacy of ADs, posted by ed_uk on November 19, 2004, at 9:09:38
Hi Ed.
> We rely on double blind trials to demonstrate efficacy though!
Have there ever been double-blind trials determining the efficacy of parachutes versus placebo in skydiving?
The problem with the studies in the way they are currently designed and interpreted is that the rate of placebo response is so high. I bet if the selection criteria were to treat people with severe depression presenting with psychomotor retardation, the results would be different.
Frederick Quitkin, MD, has paid quite a bit of attention to the placebo response and its interpretation in double-blind protocols along with rating bias:
http://ajp.psychiatryonline.org/cgi/content/full/157/3/327
- Scott
Posted by ed_uk on November 19, 2004, at 11:31:10
In reply to Re: Demonstrating the efficacy of ADs, posted by SLS on November 19, 2004, at 10:26:54
> Hi Ed.
>
> > We rely on double blind trials to demonstrate efficacy though!
>
> Have there ever been double-blind trials determining the efficacy of parachutes versus placebo in skydiving?
>
> - ScottHello Scott,
Clearly, that's not a sensible comparison.
Personally, I do believe that ADs can be effective. As with almost all drugs, their impact has often been overexaggerated.Ed.
PS. Thanks for the link to the article
Posted by ed_uk on November 19, 2004, at 13:39:44
In reply to Re: Demonstrating the efficacy of ADs, posted by ed_uk on November 19, 2004, at 11:31:10
Scott, you confused me. When you made the comment about the parachute I felt like you were insulting me but I wondered if you were just making a joke. I guess that can be a problem with the internet, you never really know what people mean.
Ed
Posted by SLS on November 19, 2004, at 14:37:43
In reply to Re: Demonstrating the efficacy of ADs, posted by ed_uk on November 19, 2004, at 13:39:44
> Scott, you confused me. When you made the comment about the parachute I felt like you were insulting me but I wondered if you were just making a joke. I guess that can be a problem with the internet, you never really know what people mean.
>
> Ed
Hi Ed.Yes. It was meant to be facetious. Sorry. I should have included an emoticon.
:-)
Take care.
- Scott
Posted by Dan Perkins on November 19, 2004, at 18:15:07
In reply to Re: Demonstrating the efficacy of ADs » ed_uk, posted by SLS on November 19, 2004, at 14:37:43
SLS,
I know you were joking, but I've been on a variety of ADs (15 of them) for over ten years and I've been skydiving only once. I'm sure that a parachute is better than no parachute, but after 10+ years on a variety of antidepressants I'm not nearly as confident about their efficacy as I am about the parachute.
Yes, ADs seem to work some of the time for some of the people, but I do think their efficacy as a drug class has been way overstated.
Posted by SLS on November 20, 2004, at 9:24:25
In reply to Re: Demonstrating the efficacy of ADs, posted by Dan Perkins on November 19, 2004, at 18:15:07
Hi.
> Yes, ADs seem to work some of the time for some of the people, but I do think their efficacy as a drug class has been way overstated.
How so?
- Scott
Posted by ed_uk on November 20, 2004, at 16:02:13
In reply to Re: Demonstrating the efficacy of ADs » ed_uk, posted by SLS on November 19, 2004, at 14:37:43
Hi!
Sorry, I'm a bit hypersensitive sometimes.
Regards,
Ed.
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.