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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by Ofan on August 7, 2003, at 3:21:51
Greetings, all.
I'm hoping someone more biochemically literate than I am can shed some light on a nagging question...
I have recently started on Wellbutrin (I am concurrently taking Celexa for OCD, but it isn't doing enough for the depression I'm also experiencing.) One difficulty I have with switching or adding medications (and staying on them once switched) is a fear of drug toxicity.
As is usual, I researched the drug as thoroughly as my limited knowledge of neurobiology allows. I discovered that bupropion is chemically rather similar to diethylpropion, a drug apparently used to treat obesity. Further research yielded
several journal abstracts indicating a level of neurotoxicity associated with diethylpropion, related to oxidative stress and excitotoxicity.So here's the question: Given the chemical similarity between bupropion and diethylpropion, is it possible that bupropion might exhibit
neurotoxicity as well?Anyone have any thoughts on this?
Posted by Mimi on August 7, 2003, at 11:55:27
In reply to Wellbutrin neurotoxicity?, posted by Ofan on August 7, 2003, at 3:21:51
> Greetings, all.
>
> I'm hoping someone more biochemically literate than I am can shed some light on a nagging question...
>
> I have recently started on Wellbutrin (I am concurrently taking Celexa for OCD, but it isn't doing enough for the depression I'm also experiencing.) One difficulty I have with switching or adding medications (and staying on them once switched) is a fear of drug toxicity.
>
> As is usual, I researched the drug as thoroughly as my limited knowledge of neurobiology allows. I discovered that bupropion is chemically rather similar to diethylpropion, a drug apparently used to treat obesity. Further research yielded
> several journal abstracts indicating a level of neurotoxicity associated with diethylpropion, related to oxidative stress and excitotoxicity.
>
> So here's the question: Given the chemical similarity between bupropion and diethylpropion, is it possible that bupropion might exhibit
> neurotoxicity as well?
>
> Anyone have any thoughts on this?Ofan,
Wellbutrin was definitely toxic to my system. My heart raced dangerously and I felt I would pass out. Needless to say, I axed that.
I do well on Celexa, but also take Seroquel for depression. Risperdal & Zyprexa work well also, though Zyprexa causes weight gain.
Mimi
Posted by stjames on August 7, 2003, at 17:00:11
In reply to Re: Wellbutrin neurotoxicity? » Ofan, posted by Mimi on August 7, 2003, at 11:55:27
> Wellbutrin was definitely toxic to my system. My heart raced dangerously and I felt I would pass out. Needless to say, I axed that.
That is an effect of nor-adrenalin and NOT a toxic effect.
Posted by pianolady on August 11, 2003, at 1:41:44
In reply to Re: Wellbutrin neurotoxicity?, posted by stjames on August 7, 2003, at 17:00:11
To consider whether Wellbutrin/Zyban is a neurotoxin, the definition of neurotoxin must be clearly outlined. According to my psychopharmacology textbook, "Drugs and Human Behavior", 4th Ed., David M. Grilly, a neurotoxin is "a substance that causes the destruction of neural tissue". While no one can be completely certain of the long-term effects (20, 30, 50, 70, etc. years from now) of drugs being used today; it is reasonable to accept that Wellbutrin will not kill brain cells. A more accurate explanation might be that over time the neurotransmitters in the brain may become accustomed to over or under producing particular neurotransmitters because of the illness we suffer from or because of the extended use of medications to treat psychiatric illnesses. Over extended time, these NT (neurotransmitters) may change to the point that the pre- and post-synaptic NTs are affected for increasingly significant lengths of time.
The long and short of it is this: It's unlikely that Wellbutrin will "kill" brain cells, but our brain chemistry may be altered with long-term usage. (Unknown whether this is good, bad, or of no consequence).
Posted by Ofan on August 11, 2003, at 15:33:46
In reply to Re: Wellbutrin neurotoxicity?, posted by pianolady on August 11, 2003, at 1:41:44
> According to my psychopharmacology
> textbook, "Drugs and Human Behavior", 4th Ed., David M. Grilly, a neurotoxin is "a substance that causes the destruction of neural tissue".Essentially, this is what I take the word neurotoxin to mean, as well. However, I would also include the type of toxicity I have read may be caused by MDMA and similar substances, i.e. not necessarily brain cell death, but long-term damage or dysfunction of cellular components (degeneration of axons, etc.)
> The long and short of it is this: It's unlikely that Wellbutrin will "kill" brain cells, but our brain chemistry may be altered with long-term usage.
> (Unknown whether this is good, bad, or of no consequence).I wonder if there are any studies looking into these effects?
At any rate, thank you all for your responses.
-O
Posted by mtdew on November 19, 2003, at 20:51:40
In reply to Wellbutrin neurotoxicity?, posted by Ofan on August 7, 2003, at 3:21:51
I would say it's quite likely, at least using a broader definition of neurotoxicity. The majority of stimulants are neurotoxic. Amphetamine neurotoxicity is well known. Wellbutrin is gentler than amphetamine, in a sense, in that it blocks reuptake of 5-HT, DA, and NE, whereas amphetamine dumps them. However, other reuptake blocking drugs have been shown to be neurotoxic. Prozac and Zoloft can cause the same changes to serotonin cells as MDMA, which dumps serotonin. Cocaine is primarily a reuptake blocker, but it has been shown to cause damage (including cell death, I think) in animals after 3-5 days of constant exposure. The relative gentleness of reuptake blockers over releasers seems to only buy time. Effects that are subtle at first will become pronounced after long-term exposure. If you are worried by such abstractions as the risk of long-term brain damage, you are better off staying away from psychiatric drugs. The lack of evidence for damage from a particular substance should not be seen as evidence of safety. Also remember that when you ask questions like this to people in the mental health community, you are not likely to get an unbiased answer, considering that pretty much everyone is already sold on the idea of psychiatric drugs. I hope I don't sound alarmist, but I personally am concerned about brain damaging drugs, and it was unreasonably difficult for me to find the information I mentioned above. I think a good reference for more information is Dr. Peter Breggin's books (although I haven't read them).
Hope this helps.
> Greetings, all.
>
> I'm hoping someone more biochemically literate than I am can shed some light on a nagging question...
>
> I have recently started on Wellbutrin (I am concurrently taking Celexa for OCD, but it isn't doing enough for the depression I'm also experiencing.) One difficulty I have with switching or adding medications (and staying on them once switched) is a fear of drug toxicity.
>
> As is usual, I researched the drug as thoroughly as my limited knowledge of neurobiology allows. I discovered that bupropion is chemically rather similar to diethylpropion, a drug apparently used to treat obesity. Further research yielded
> several journal abstracts indicating a level of neurotoxicity associated with diethylpropion, related to oxidative stress and excitotoxicity.
>
> So here's the question: Given the chemical similarity between bupropion and diethylpropion, is it possible that bupropion might exhibit
> neurotoxicity as well?
>
> Anyone have any thoughts on this?
Posted by Ofan on November 19, 2003, at 22:24:23
In reply to Re: Wellbutrin neurotoxicity?, posted by mtdew on November 19, 2003, at 20:51:40
> 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
Posted by Viridis on November 20, 2003, at 1:48:02
In reply to Re: Wellbutrin neurotoxicity? » mtdew, posted by Ofan on November 19, 2003, at 22:24:23
The problem is that depression and anxiety themselves appear to cause brain damage, so avoiding meds may not be a viable neuroprotective strategy (not to mention the damage these conditions can do to the rest of your body).
Posted by tai daluna on November 20, 2003, at 7:21:43
In reply to Re: Wellbutrin neurotoxicity?, posted by Viridis on November 20, 2003, at 1:48:02
i recently read in scientific american that the newer AD's may actually cause growth of new brain cells (aka neurogenesis) in the hypothalamus. my big worry on reading that was: cell growth= eventual cancer???? hmmmm... taking my chances, tho, because i couldn't imagine what my life would be like w/o my effexor. well, actually, i can, and it involved continual terror from my very damaged (by drugs and violence) brain.
wellbutrin sucked for me too... lol... i feel your pain! wellbutrin gave me a panic attack so bad my face and hands went numb. guess i'd been hyperventilating for awhile w/o realizing it.
peace. tai
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
This is the end of the thread.
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