The tale of one troubled would-be antidepressant has just been published in the form of a clinical trial that was terminated early when the parent company went under. But another company came along to save the day, so the drug might live on.
Amitifadine is a triple reuptake inhibitor (TRI). What's that? Prozac and other SSRI antidepressants work by blocking the reuptake of serotonin in the brain thus increasing levels of serotonin. Some other antidepressants block the reuptake of serotonin and noradrenaline, and these dual reuptake inhibitors may be slightly better than SSRIs (although maybe not).
TRIs take this one step further: they add a third monoamine neurotransmitter, dopamine, to the list. If two monoamines are better than one, three ought to be even better... right?
This was a clinical trial of amitifadine vs placebo in depressed adults. It was originally designed to have 200 depressed people, but it only got to 63 patients before the money ran out:
The study was initiated in April 2008 and was halted by the sponsor, DOV Pharmaceuticals, early in December 2008 due to lack of funding.DOV were a small company best known in the financial world for the fact that their stock crashed spectacularly on the first day they went public on the markets. Investors who lost out subsequently sued the company and their main underwriters, a certain outfit you may have heard of called Lehman Brothers.
After various (non-psychiatry) projects failed, DOV were bought out by a certain Euthymics Bioscience. DOV's old website, dovpharm.com, now offers Canadian Cialis. Don't wait! Order the cheapest medications now!
What a sad fate.
When Euthymics bought DOV, they also bought the rights to DOV 21,947 which they dubbed amitifadine. The takeover happened in June 2010, so I guess that after DOV pulled the plug on the trial in 2008, Euthymics came along and decided to try to finish the development of amitifadine. The lead author on the present paper is Chief Medical Officer at Euthymics.
So what did they get for their money? Is amitifadine a goose that will lay some golden eggs, or the latest turkey?
Take a look:
The non-significant benefit over placebo on the HAMD was 3.1 points. How does that compare to other drugs? It's impossible to say for sure, but there are some reasons to think that it's nothing special.
Patients in this study had very severe depression, with a baseline HAMD17 score of about 29.5. We know that the effect of antidepressants over placebo is correlated with severity. For what it's worth, with existing antidepressants, a baseline HAMD score of 29.5 would be expected to translate into a drug-placebo difference of about 4 HAMD points according to Fournier et al or about 5 in Kirsch et al.
Plus, the odds were stacked in the drug's favour in this study. To get into the trial, patients needed to have shown a "significant clinical improvement" to at least one previous antidepressant. Anyone who'd failed to improve on two or more different drugs was excluded.
In terms of side effects, there weren't many, and people on the drug actually reported no more adverse effects than those on placebo, in total. It lowered blood pressure and raised heart rate slightly. However, the small sample size is an issue here as well. The only way to know whether it's really better tolerated than other drugs would be to do a direct comparison.
Overall, while amitifadine looks like it works to some extent, it's anyone's guess whether it will offer any advantages over existing, cheap drugs - a verdict that Neuroskeptic readers have heard before.
Tran P, Skolnick P, Czobor P, Huang NY, Bradshaw M, McKinney A, & Fava M (2011). Efficacy and tolerability of the novel triple reuptake inhibitor amitifadine in the treatment of patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Journal of psychiatric research PMID: 21925682
8 comments:
Could be used instead of a betablocker. Better, more perfusion with higher heart rate whilst lower bloodpressure.
If it has no side effects, why not. Betablockers are a menace to your health.
What with the greying of western society would sell like hotcakes
I left a comment on your "How blind is double blind" post on antidepressant just a few minutes ago. I would like your thoughts on it if you could. I post here because you don't have a "last comments" list and the post is old.
Is it not the case that drugs that raise levels of dopamine are addictive? In particular, doesn't cocaine work by blocking the reuptake of dopamine?
Do they check to see if a psychoactive drug is non-addictive, as well as safe and effective before licensing?
Yes, cocaine and amphetamines work by blocking dopamine reuptake (and increasing dopamine release in the case of amphetamine).
This drug however only has a weak dopamine reuptake effect.
However you still might find people deliberately taking high doses to get high.
http://neuroskeptic.blogspot.com/2010/03/how-blind-is-double-blind.html
Surely, the larger the sample needed to show the effectiveness of a treatment, the less effective the treatment actually is.
I reckon I'd only have to shove a few people out of a plane, either with or without a parachute, to show that a parachute was an effective treatment for falling out of a plane. I'd question it's effectiveness if I needed 1000 people to demonstrate this.
Paul: Yes, exactly right.
Please one more post about that.I wonder how you got so good. This is really a fascinating blog, lots of stuff that I can get into. One thing I just want to say is that your Blog is so perfect
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