 |
 |
Ariela: You go to the heart of the matter with your questions. #1 The only PROVEN reason to use a Monoamine Oxidase B Inhibitors (selegiline) is to extend the effect of levodopa. Using selegiline in combination with any of the dopamine agonists is not of any proven value. The likelihood is that rasagiline will turn out to be the same. MAOB inhibitors are not known to extend the effect of dopamine agonists, and there is no theoretical reason why they should. #2 The use of MAOB inhibitors as FIRST therapy is predicated upon the SPECULATION that they may be neuroprotective, and somehow delay the progression of the disease. In the case of selegiline, this proved to be wrong in humans with PD. Given the failure of selegiline in this respect, there is no reason to expect that rasagiline would be different, but the drug company is proceding with research in this direction hoping that it might, and is already beating the drums. #3 The logic that "any postponement in levodopa start is worth the trouble" is highly controversial. It is promulgated primarily by the drug companies who are trying to sell the dopamine agonists - frightening PWP that early use of levodopa causes earlier dyskinesias. Although many neurologists agree, the data are based on incomplete and flawed studies designed to promote the use of the agonists. The final answer with respect to this question is yet to come. In the meantime, some people avoid early use of levodopa "just in case." #4 Many of the ANTIdepressants are reuptake inhibitors - some inhibit the reuptake of catecholamines (including dopamine), others inhibit the reuptake of serotonin. The antiparkinsonian drugs (levodopa or the agonists) do not cause the serotonin syndrome. With selegiline or rasagiline there may be some possibility of precipitating the serotonin syndrome when mixed with other antidepressants, but not with the antiparkinsonian drugs. This is unlikely, however, but theoretically possible. #5 Your observation about the length of studies is very logical. Indeed, we should have learned that lesson well from the DATATOP Selegiline study. The initial data (six month follow-up) was initially interpreted as showing some neuroprotective effect. The longer follow-up (five years) showed that there was no significant difference. Jorge A. Romero, MD ----- Original Message ----- From: "ariela" <[log in to unmask]> To: <[log in to unmask]> Sent: Sunday, November 04, 2001 4:21 PM Subject: Re: Fw: new clinical trials / Rasagiline > thank you, dr. romero. i was hoping one of the MDs on the list would > share their view on this subject. > > but now that you have -- and got me even less clear on this drug's behavior... > :) -- i wonder if you'd be so good and explain the following as well: > > 1. > although selegiline is indeed indicated for extending the duration of > levodopa's effect, i was under the impression that nevertheless it has > currently been prescribed as a FIRST mode of therapy -- usually in conjunction > with dopamine-agonist drugs (such as requip, etc). moreover, it's given > BEFORE sinemet is started, the logic being that any postponement of levodopa > start -- even if not being a strictly corrective treatment -- is worth > the trouble. > > 2. > since selegiline has those amphetamine-like properties, yet the dopamine > agonists act more like depressants (by definition, they are re-uptake > inhibitors), then isn't mixing these drugs dangerous? wouldn't such > practice expose a patient to a reaction not unlike that of serotonin > syndrome? > > 3. > re. that "confounding strong placebo effect" -- if memory serves, a recent > study showed that when it comes to any dopaminergic neurotrasmitter problems, > the placebo effect is stronger, longer and more serious (because of the > role dopamine plays in emotions etc...). shouldn't then ALL pd-related > studies that are shorter than one year, or those not tracked with long > follow-ups, be considered inconclusive? > > thanks again, > ariela > > ---- > Jorge A Romero MD <[log in to unmask]> wrote: > > Ariela: > > Beware of drug company promotions and salesmanship. It may still rain > on the Rasagiline parade! > > It is not clear that the so-called "amphetamine like properties" in > selegiline are a disadvantage. Indeed, selegiline has antidepressant > and "energizing" qualities, probably in part due to those same qualities > which the drug company for the other side has focused on. > > In addition, selegiline has antidepressant qualities (which rasagiline > undoubtedly shares) due to its abiity to delay the metabolism of > catecholamines, the same reason that it may be useful in Parkinson's > Disease, by delaying the metabolism of dopamine - extending the duration > of action of a single dose of levodopa to some extent. > > The problem with selegiline is that it did not meet the expectations > of the DATATOP study in delaying the progression of PD. After much hoopla, > and enormous profits to Somerset and Sandoz, it fell flat on its face > when the longer term follow-up studies became available, showing no delay > in progression of PD. > > Thus, the only remaining use for selegiline was to try to extend the > duration of the effect of each dose of levodopa, which was, in fact, > the indication for which the FDA approved it in the first place. I am > not aware that Rasagiline claims any EXTRA effect from selegiline - and > the only selling point to date is this "lack of amphetamine like qualities," > which is nothing more than an empty claim to emphasize a difference which > is not known to be important. > > > improvements were greater for rasagiline than for placebo at all > > time points and for all doses, but were ***INSIGNIFICANT*** due to > a > > "confounding strong placebo effect," > > That means that the study was UNABLE to show that the drug was better > than the placebo control. > > It is interesting that they are claiming that the rasagiline group was > better at 18 weeks after washout, althought the difference was not > significant. It seems they are positioning themselves to make a claim > for delay in the progression of the disease. However, remember that > selegiline made that claim on the basis of 6 months' data, and the five > year data proved them wrong. > > It would be like selling you a minivan with three doors instead of four,and > claiming that one door less makes it safer, when most manufacturers are > promoting the four door models as more convenient. > > We all want newer and better drugs for PD. Drug companies will do > everything they can to sell you their drugs. Buyer beware!!! > > Jorge Romero, MD > > ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn