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Re: Wellbutrin neurotoxicity?

Posted by mtdew on November 20, 2003, at 22:40:53

In reply to Re: Wellbutrin neurotoxicity? » mtdew, posted by Ofan on November 19, 2003, at 22:24:23

That sounds like the same paper I read. You have to take into account the fact that rats have to be given higher doses in mg/kg than humans to produce the same level of exposure. I think this is partly due to the rats' clearing substances from their bodies faster. Also, higher doses are used in toxicology studies like these so that the changes are easy to observe in a short timeframe. If a more reasonable dose produced changes in, say, 0.00001% of axons, it would be much harder to find them, and to say conclusively that they resulted from the drug and weren't just random defects. In humans, the drugs are typically used for months, or years, at a time. Hence, even though the changes probably don't occur at measurable levels over the course of a few days at normal human doses, it's entirely possible that they add up over time and become significant. This study doesn't prove or disprove that conjecture. To get a better answer to the human question, longer studies using lower doses are needed, preferably in primates. I think the authors of the original study are planning something along those lines, but we'll have to wait.

It goes without saying that patients and doctors need to evaluate the potential risks and benefits of taking a particular drug. The thing that bothers me is that the risks are so poorly understood or so poorly communicated that it's almost impossible to make an informed decision. Why was this study only done in 1999, when Prozac has been out since around 1980, and the toxic effects of MDMA and fenfluramine have been known about for years? Because nobody has a strong financial or political interest in exposing the risks of prescription drugs. It might seem strange, but the risks of street drugs are much better understood, thanks to the well-funded efforts of NIDA. As a result, one of the best ways to find clues to the possible toxic effects of antidepressants is to look at this extensive literature, particularly at street drugs with similar methods of operation in the brain. This is why I cited cocaine, as another 5-HT, DA, and NE reuptake inhibitor. In a perfect world, would you, the patient, have to do this yourself and speculate? No. But that is the state of things, when most of the research is done by entities with a financial interest in selling as many drugs as possible.

And one last point; I suspect that the risk-benefit analysis when done by the FDA uses assumptions like the target group is non-functional and at great risk of suicide. When seen in these terms, a drug doesn't have to show very much safety to pass regulatory muster. Just something to think about if you are considering an off-label use or have only moderate dysthymic depression.

Sorry to editorialize a little.

> > Prozac and Zoloft can cause the same changes to > serotonin cells as MDMA, which dumps serotonin.
>
> I'm curious about this... do you have any references I could pursue? The only thing I've been able to find is a study indicating morphological changes to serotonergic terminals with very high doses (30+ times the therapeutic dose), but I've not heard of anything looking at dose levels closer to what humans actually take.
>
>
>
> Regards,
> Ofan


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URL: http://www.dr-bob.org/babble/20031116/msgs/281922.html