A cross post from Furious Seasons.
I'm not sure how many of you saw the item on my site late yesterday, but there is a very important study out in PLoS Medicine (meaning it's online and free), asserting that several anti-depressants aren't up to clinical measures of efficacy when it comes to treating depression. The study was lead-authored by Irving Kirsch, a psychologist at the University of Hull in the UK.
It is a very complicated study when it comes to the statistical analysis, but these were the very studies that the makers of Prozac, Paxil, Effexor and Serzone submitted to the FDA to gain approval for these drugs in treating depression. The researchers used as their clinical measure an index created by the National Institute for Clinical Excellence (NICE), which is a British agency. The NICE standard is that for an anti-depressant to be considered efficacious it has to beat a placebo by at least three points on the Hamilton Depression rating scale. Anything less, and it's all placebo effect that's being measured in essence, or it's very expensive pharmaceutical equivalent.
This study comes five weeks after a separate study in the New England Journal of Medicine examined clinical trials data submitted to the FDA for all 12 of the new generation anti-depressants and found that, owing to numerous unpublished studies, pharma companies had been overstating anti-depressant efficacy by about 30 percent.
I won't bore you with all the numbers from the British study but it basically concludes what the NEJM study did. Here's the conclusion from the PLoS paper:
"Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication."
In other words, if the drugs work at all, then it's for severely depressed patients, but they don't outperform placebo that much there either. That is simply a staggering conclusion--and validates much of what I've been writing for the last few years--but I need to be fair and point out that the study only examined four drugs and that these were only the FDA approval studies, not the post-marketing studies of these drugs which are much more extensive. Then again, given how badly post-marketing studies tend to be twisted and contorted to produce positive results, I have no problem with relying on these FDA studies.
The drugs in the study beat placebo by 1.8 points on the Hamilton scale.
Also, a couple of pharma companies had some thoughts for the British press (I've not seen any US press accounts of this study yet beyond this slim Reuters piece):
Lilly, maker of Prozac, was apparently steamed and issued a statement, which isn't on the company's website as yet, so here's the Guardian's account:
"'Extensive scientific and medical experience has demonstrated that fluoxetine is an effective antidepressant,' it said in a statement. 'Since its discovery in 1972, fluoxetine has become one of the world's most-studied medicines. Lilly is proud of the difference fluoxetine has made to millions of people living with depression.'"
GlaxoSmithKline, maker of Paxil/ Seroxat, was similarly upset:
"A spokesman for GlaxoSmithKline, which makes Seroxat, said the authors had failed to acknowledge the 'very positive' benefits of the treatment and their conclusions were 'at odds with what has been seen in actual clinical practice.'"
If there were very positive benefits in the data they'd analyzed, I expect the researchers would've reported it.
"He added: 'This analysis has only examined a small subset of the total data available while regulatory bodies around the world have conducted extensive reviews and evaluations of all the data available, and this one study should not be used to cause unnecessary alarm and concern for patients.'"
For the last few years, the news on the anti-depressant front hasn't been good. There were the black box warnings in 2004 and 2007. Then, there were very disappointing results from the STAR*D and STEP-BD studies. Then, there was the NEJM study. And, now this one.
So at this point I think it's fair to ask: Why are anti-depressants the go-to choice for addressing depression when the evidence for their use is very shaky and the side effects of these drugs are well known? Why were they approved by regulators? And, have all of us who've taken anti-depressants in the last 20 years just been taking a big old placebo the whole time?