Posted by linkadge on July 15, 2006, at 22:31:49
In reply to Re: couldn't have said it better myself, posted by Klavot on July 15, 2006, at 7:32:31
>1. Some critics have said that the placebo >success rate in this study was unusually high, >that in other similar studies (similar in terms >of duration, patient profile etc.) the placebo >remission rate is often much lower. So perhaps >the placebo success rate in this particular >study is a statistical aberration.
Of course, it could be a statiscial abberation. Though the drug responce could have just as likely been a statiscal aberation.
>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.
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!
>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.
The >role of low serotonergic activity in suicidal >ideation is well correlated.
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.
>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.
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.
>6. Zoloft gave a greater improvement in mean HAM->D, GAF, BDI, SDS and CGI scores than placebo, >admittedly not all of them statistically >significant.>7. 22 % of placebo patients >reported "forgetfulness", compared with 12 % >Zoloft patients. Thus it may be that, on >average, Zoloft actually improves memory (this >has certainly been my personal experience).
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.
No comment.
It is easy in hindsight to speculate why a drug failed.
Linkadge
poster:linkadge
thread:662854
URL: http://www.dr-bob.org/babble/20060709/msgs/667415.html