Posted by Klavot on July 16, 2006, at 3:11:35
In reply to Re: couldn't have said it better myself, posted by linkadge on July 15, 2006, at 22:31:49
> >2. The average dose of Zoloft used was >relatively low (75 mg / day during the acute >phase and 89 mg / day during the maintenance >phase) especially considering that the mean 17->point HAM-D score for the Zoloft arm was a >relatively high 22.5.
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> The dose of SJW could have been increased too, though higher doses often do not correlate to better responces. The placebo dose could have been increased, that can work too!Personally I am not interested in the SJW aspect of the study (since I've never much subscribed to alternative modalities). Rather, I am concerned over the apparent sub-placebo efficacy of Zoloft. The fact remains - and there is no way to maneuver around this - that the dose of Zoloft used was relatively low.
> >3. Patients with a HAM-D suicide score of more >than 2 were excluded for ethical reasons. The >role of low serotonergic activity in suicidal >ideation is well correlated. Had these patients >been included in the study, this would likely >have improved the outcome of the Zoloft arm >relative to placebo.
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> The >role of low serotonergic activity in suicidal >ideation is well correlated.
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> In some ways that is a perpetuated myth that people base a lot of assumptions on. It essentially is not true. The only real way to get an accurate idea of serotonergic functioning is post mortem. Those with suicidal "ideation" are not yet dead. In addition, no consistant findings regarding typtophan depletion tests, tryptophan hydroxylase genes, or serotonin transporter genes have ever been made in suicidal patients. Altered serotonergic binding has been noted, but that is not necessarily due to "low serotoniergic function". Some have suggested too that "low serotonin" is really just a marker of impulsivity, rather than depression at all. Then there is the recent discovery that serotonergic drugs can often make people suicidal. It all throws a kink in the theories.
>I read somewhere - though I cannot back this up with any references - that biopsies of the brains of suicide victims tend to show low serotonin levels.
Anyway, this particular study was skewed in favour of nonsuicidal patients, and as SLS points out in his cogent analysis of placebo efficacy, had those patients been included, the results of the Zoloft arm may well have been different.
> >4. While Zoloft did not differ to a >statistically significant extent from placebo in >producing full remission, the case of strictly >partial remission is another story. Zoloft >produced strictly partial remission in some 26 % >of patients compared to the 13 % placebo rate.
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> Yeah, that was due to their crafty "second measures" if I recall. Essentially, once they saw that the drug didn't perform better than placebo, they intoroduced a set of second measures which of course showed the drug was better than placebo. But, you can't do that. You can't just introduce new measures after the study has been started.
>Since there are baseline measurements for these secondary measures, I am not sure that these measurements were only introduced afterwards. Your claim that they decided afterwards to include these measurements to save face is mere speculation. And again, the fact remains that Zoloft did outperform placebo on these measurements, irrespective of any possible dubious motivations for including these measurements.
> Serotonergic drugs may improve acute memory recall. They can act like stimulants for many patients. Memory problems have been associated with long term SSRI use, so who knows how this affect pans out.
>> >8. As far as I can tell, all the authors of the >study have financial interests in Pfizer.
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> No comment.It is interesting how, when a study supports the efficacy of a drug, suddenly issues of collusion between researchers and pharmaceutical companies are raised, while when a study such as this one finds no statistically significant super-placebo efficacy in terms of full remission, then the industry involvement of the authors is a suddenly a non-issue.
> It is easy in hindsight to speculate why a drug failed.
>The drug did not "fail". The whole point that I am making is that the coverage given of this study in the popular media has been highly distorted. Furthermore, the points raised above are based on fact rather than speculation.
> Linkadge
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poster:Klavot
thread:662854
URL: http://www.dr-bob.org/babble/20060709/msgs/667432.html