Posted by jrbecker on October 27, 2005, at 16:36:25
In reply to Re: Valdoxan--caution about no withdrawal, posted by ravenstorm on October 27, 2005, at 11:04:48
> OH, this drug sounds so promising. I wish it were being submitted to the FDA!!!!!!!!!!!!!
>
> Just a caution on the wording of the claim for no discontinuation syndrome. The study indicated no withdrawal symptoms after a week of discontinuation, however, valdoxan has a much longer half life than the paxil it was compared to. Thus, discontinuation symptoms, if there are any, would not occur until sometime into the second week of stopping the drug.
>
> For most people the longer half life may indeed mean no withdrawal, but that is not guaranteed and can not be gleaned from the way it was studied/reported.
>
> I, for one, would love to try this drug. I wonder if it is possible to get a doctor in Europe to prescribe it to someone in the U.S. after it is approved?actually, agomelatine has less than a 2 hour half-life, paroxetine's is approx 24 hours. But, the withdrawal of any compound has more to do it with its biochemical mechanisms of action more than its pharmacokinetics (you're of course speaking more to the timing of withdrawal). Agomelatine has been shown to have a different antidepressant mechanism of action than than SSRIs/SNRIs and similarly, does not have the same withdrawal issues...see the following abstract (by the way, symptoms were monitored for two full weeks).
The effects of an abrupt interruption of agomelatine, a new melatonergic/serotonergic antidepressant, were explored in a double-blind, placebo-controlled study. Paroxetine was used as active control. After 12 weeks of double-blind treatment with agomelatine 25 mg/day or paroxetine 20 mg/day, sustained remitted depressed patients were randomized for 2 weeks, under double-blind conditions, to placebo or to their initial antidepressant treatment. Discontinuation symptoms were assessed at the end of the first and second week of discontinuation with the
Discontinuation Emergent Signs and Symptoms (DESS) checklist. One hundred and ninety-two sustained remitted patients were randomized to the 2-week discontinuation period. Patients who discontinued agomelatine did not experience more discontinuation symptoms than those who continued on agomelatine. Patients who discontinued paroxetine for placebo experienced significantly more DESS discontinuation symptoms, during the first week,compared to those who continued with paroxetine (respective mean number of emergent symptoms: 7.3± 7.1 and 3.5 ± 4.1, P < 0.001). No significant difference was shown between the continuing and interrupting groups in the second week of discontinuation. By contrast to paroxetine, abrupt cessation of agomelatine is notassociated with discontinuation symptoms.Int Clin
Psychopharmacol 19:271–280 c 2004 Lippincott Williams
& Wilkins.___
This follows the same evidence that shows that withdrawal from other 5-HT2 antagonists (nefazodone, mirtazapine, APs, etc) is negligible or at least drastically lower in comparison to SSRIs/SNRIs.
As for being submitted in the US, it is in Phase III trials here. But I'm guessing the company will wait to see how it hits the market abroad before it approaches the FDA. Hopefully the EU launch will be soon (i.e., the next 4-8 months).
poster:jrbecker
thread:571357
URL: http://www.dr-bob.org/babble/20051024/msgs/572451.html