![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 7 to 31 of 39. Go back in thread:
Posted by Chris A. on March 14, 2001, at 13:53:42
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » vince, posted by ShelliR on March 14, 2001, at 12:58:48
I am trying it even though the risks are greater for females, the elderly, those who have had any brain damage and those who have had a larger lifetime cumulative exposure to D2 antagonists. Since I've had a touch of TD -buccal vermiculations and some orofacial involvement it's a bit scary. My first exposure to APs was thirty years ago, has been spotty and in very low doses. I qualify for all of the increased risk factors except possibly for age, although that is debatable. Decades of depression make one age faster.
Ziprasidone is supposed to be a gentler AP, but I am asking how that can be since it is still a D2 antagonist. My pDoc and my husband don't want to see me dead and I am desperate to end the pain. It boils down to risk vs. benefit. Nothing phamacologically active has a good effect without having undesireable side effects.
One positive early observation is that it does not knock me out like miniscule doses of Zyprexa. Since I have to drive and at least minimally function that is a plus. I haven't noticed any need to eat constantly, which is also encouraging. As far as the TD goes I'll attempt to stay on the lowest dose that alleviates symptoms and pray - a lot. My university consultant recommended it to me two years ago. When I see him again next month I'll ask him some hard questions and try to report back on his answers.
In the meantime I'm hoping it helps with my mixed/depressed bipolar, unrelenting suicidal thoughts, attention and concentration. It would also be nice to alleviate the anhedonia, anxiety and increase cognitive functioning. Perhaps I am asking a bit much. My other meds are Aricept, selegilene 10 mg, Lamictal 100 mg bid, Klonopin up to .5 mg q 24 hrs and Ambien. I just discontinued 300 of Neurontin and am in the process of discontinuing 450 mg of Trileptal. Anticonvulsants in small doses other than Lamictal tend to impair my cognition and make me drowsy without allowing me to sleep (figure that one out). It would be nice to drastically reduce the amount of meds I take. I didn't mention the hormones - Synthroid, Cytomel and the 'other'.I am hopeful about the ziprasidone and trying to keep my fear in check. Hopefully it will be as good as or better than Zyprexa in regards to TD. I tried to compare them through the literature and PDR info, but didn't come up with anything.
Here's to hope,
Chris A
Posted by ShelliR on March 14, 2001, at 15:57:51
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » ShelliR, posted by Chris A. on March 14, 2001, at 13:53:42
Chris, I did find a site, which talks about prevention and cure by taking vitamins, especially vitamin E: www.healthwell.com/healthnotes/Concern/Tardive_Dyskinesia.cfm. What is it you're on such a low dose of lamictal, since it has no bad effects? I was up to 400mg of lamictal, it definitely helps me, but I can't stand the weight gain. I keep trying to accept it, but it totally freaks me out, because I have been eating very little and doing the treadmill for 45 minutes five times a week, as well as other exercises with weights. (You might not be gaining weight on it; lots of people don't). I am also trying omega fatty acids--there has been some good success (even my pdoc says so) for both bipolar and unipolar depression. But it takes several months, I hear for it to kick in. I am feeling optimistic about it, since NIMH is doing studies on it.
Were you on zyprexa when you had signs of TD?
Maybe I will try geodon as a temporary measure until the omega kicks in. So far I have not been able to adjust to any atypical antipsychotic--but perhaps I haven't wanted to. But I will definitely increase my vitamin e. Now I take 400mg; I would increase it to 1200 daily.
I'm sorry you have had such a difficult time for so many years. I can see how taking the geodon might be worth it. Let me know how you're doing, and I will do the same if I decide to try it. Shelli
Posted by Chris A. on March 14, 2001, at 21:35:42
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » Chris A., posted by ShelliR on March 14, 2001, at 15:57:51
Shelli,
Thanks for the link. Now I know why my consultant suggested taking 2,000 IU of vit E a day. I thought it was a bit high, as it can have side effects, but so far so good. It's on my list to ask about when I see him again. Increasing intake of other antioxidants makes sense for a lot of reasons. Tardive dyskinesia is now the first reason on my list to take them.
When my TD appeared I was taking 2 mgs of pherphenazine. Some of us are just blessed with vulnerable central nervous systems. Geodon is the first atypical AP that I've been able to tolerate at all, so you're not alone there. This is day five, so it's a little early to give a full report. Perhaps it's a bit premature to take out stock in Pfizer. They make half of the meds I take.Have you found Omega 3s that you can tolerate? I was taking about nine grams daily (six of EPA and three of DHA), but haven't been able to tolerate them the last few months. I wondered if restarting anticonvulsants had anything to do with the dyspahagia. They don't seem to want to stay put after I swallow them anymore. They keep revisiting. Considering the multitude of health benefits it is definitely the way to go if it works. My preference is for Alaskan Salmon oil since it has the least probability of contamination. The last thing my brain needs is methylmercury.
I don't go above 200 mg of Lamictal because on higher doses it was speculated that it could be contributing to my ultra-rapid cycling. I'm sorry to hear about the weight gain you've experienced with it. I have names for most of the anticonvulsants and atypical APs in regards to their propensity to add the weight, but never considered one for Lamictal. How about lamotri-mountain? Not funny, is it. If I could get by on just Lamictal and Geodon without debilitating side effects it would be great. There are still days I wonder what would happen if I ditched all meds, something I preach against for those of us with bipolar. When a pharmacist asked me if I was going to be able to carry all of my meds it was a wake-up call. I would like to avoid the Klonopin and the Ambien as they probably don't enhance cognitive functioning.
Perhaps the ziprasidone will help with my tangential thinking and writing.
Thanks for caring. Keep me posted on your progress. Temporary use of an atypical AP should be fairly safe as far as TD goes.
Blessings,
Chris A.
Posted by ShelliR on March 14, 2001, at 23:46:03
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » ShelliR, posted by Chris A. on March 14, 2001, at 21:35:42
>Chris, One more thing. I also had trouble making myself take twelve huge pills a day, so recently I have begun to buy flax seeds. You can grind them up and put them in cereal, soak them overnight and drink them in juice, etc. I like the taste, actually, so I dip a teapoon of peanut butter in a tablespoon of flax seeds three times a day. I think, but am not sure, that they contain as much EPA or whatever, as omega fatty acids. I have been taking the three tbs a day, but probably ought to check and see if I need to take more or add something to it. I'm also eating fish two or three times a week. shelli
Posted by vince on March 15, 2001, at 1:05:31
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk?, posted by Lorraine on March 14, 2001, at 10:40:58
> Vince: Have you tried Effexor. It has AD and anti-anxiety properties. It worked for me for a couple of years, then the weight gain and sexual side effects got to my husband (LOL). Withdrawal from Effexor was tough, but they say add a long life AD (like Prozac) when you taper off for a few days and the withdrawal is easier. If you try it, I'd recommend a low carb diet because in my experience the weight gain was caused by carb craving and low carb diets curb the cravings. Good luck.
Lorraine,
Thanks for your reply. I have tried effexor. My pdoc had me take it up to a very high dose. He wanted me to go to 450mg but I was only able to go to 400mg/day before the side effects became intolerable. I can't remember getting any relief from depression at all. I do remember that I completely lost interest in sex. My wife thought that maybe I had found a mistress.
I think I've tried every main stream drug treatment and every combination and permutation of the above that is commonly tried. I've also tried the overseas pharmacy route on a few occations. I tried a round of ECT many years ago - forget that! Pun intended. So now I don't really consider anything unless it is a ways off the beaten path. Right now I'm on Neurontin about 1200 to 1600 per day. It kills the intense psychological pain that drives my suicidal ideation. But it doesn't do much for all the other symptoms of depression. I'm looking for something else that might help. Ziprasidone sounds interesting and also mirapex. My pdoc needs to read psychobabble so he doesn't think that I'm just making up new things to try.
Vince
Posted by steve on March 15, 2001, at 2:21:10
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » vince, posted by ShelliR on March 14, 2001, at 12:58:48
>
> > Is the risk of tardive diskinesia greater with ziprasidone than with Zyprexa or other drugs in the same class?
>
> My pdoc has had one patient so far develop TD on a moderate dose(her description) of risperidol. She says the likelihood of developing td with either zyprexa or geodon is less likely because risperidol is more similar to the regular antipsychotics. But I don't know what "less likely" really means. She has left me a sample package of geodon, but I am very scared to try it.
>
> Incidently, in most cases, if td is picked up early, it can be reversed, says my pdoc, in about four months. shelliI really don't think your shrink is doing you a favor by suggesting that TD is something one either has or doesn't have. TD is caused by the APDs killing neurons off, which they all do by their very mode of action. The only unknown is if it the neurotoxicity will suffice to inflict disabling neurological damage or not. A much better analogy would be say with lead poisoning, which some times does cause substantial CNS disturbacnes, and sometimes kills, but not always either.
I don't have an opinion on what you should do, nor would I deign to speak on your behalf. But I do think that you should know exactly what you are getting yourself into before you go for it, Lord knows I wished I had.
S.
Posted by Lorraine on March 15, 2001, at 9:48:48
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » Lorraine, posted by vince on March 15, 2001, at 1:05:31
Neurontin doesn't seem to be doing much for my physical anxiety. I'm at 900 mg. Did it do much for yours? I've already started my doctor education program about Mirapex. I'm thinking to add it to the Selegiline I'm taking.
Posted by vince on March 15, 2001, at 11:05:51
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk?, posted by Lorraine on March 15, 2001, at 9:48:48
> Neurontin doesn't seem to be doing much for my physical anxiety. I'm at 900 mg. Did it do much for yours? I've already started my doctor education program about Mirapex. I'm thinking to add it to the Selegiline I'm taking.
Lorraine, - Neurontin has kind of a calming effect for me; a lot like benzo's. At first I would get really jittery when it started to wear off, but that has subsided some. If I get my dose to high then I seem to crash on it after a few days so I have to keep it relatively low.
Do you know if Mirapex would have the type of TD risk as ziprasidone? What causes TD? Is it the action on dopamine? - Vince
Posted by JohnX on March 15, 2001, at 23:36:26
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » ShelliR, posted by steve on March 15, 2001, at 2:21:10
> I really don't think your shrink is doing you a favor by suggesting that TD is something one either has or doesn't have. TD is caused by the APDs killing neurons off, which they all do by their very mode of action. The only unknown is if it the neurotoxicity will suffice to inflict disabling neurological damage or not. A much better analogy would be say with lead poisoning, which some times does cause substantial CNS disturbacnes, and sometimes kills, but not always either.
> > S.
I thought TD was primarily caused by a lack of dopamine or blockade of D2 receptors spawning more D2 receptors? The inclusion of 5ht-2 antagonists in newer anti-psychotics was to increase the dopamine release in those receptors sensitive to TD.-John
Posted by steve on March 16, 2001, at 3:51:38
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » steve, posted by JohnX on March 15, 2001, at 23:36:26
>
> > I really don't think your shrink is doing you a favor by suggesting that TD is something one either has or doesn't have. TD is caused by the APDs killing neurons off, which they all do by their very mode of action. The only unknown is if it the neurotoxicity will suffice to inflict disabling neurological damage or not. A much better analogy would be say with lead poisoning, which some times does cause substantial CNS disturbacnes, and sometimes kills, but not always either.
> > > S.
>
>
> I thought TD was primarily caused by a lack of dopamine or blockade of D2 receptors spawning more D2 receptors? The inclusion of 5ht-2 antagonists in newer anti-psychotics was to increase the dopamine release in those receptors sensitive to TD.
>
> -JohnThat theory is no longer operative. Current thinking is that TD is when the brain damage reaches a critical mass. There might be a case to be made for the treatment, but the fact remains that it does cause brain damage.
S.
Posted by JohnX on March 17, 2001, at 7:20:02
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk?, posted by steve on March 16, 2001, at 3:51:38
> >
> > > I really don't think your shrink is doing you a favor by suggesting that TD is something one either has or doesn't have. TD is caused by the APDs killing neurons off, which they all do by their very mode of action. The only unknown is if it the neurotoxicity will suffice to inflict disabling neurological damage or not. A much better analogy would be say with lead poisoning, which some times does cause substantial CNS disturbacnes, and sometimes kills, but not always either.
> > > > S.
> >
> >
> > I thought TD was primarily caused by a lack of dopamine or blockade of D2 receptors spawning more D2 receptors? The inclusion of 5ht-2 antagonists in newer anti-psychotics was to increase the dopamine release in those receptors sensitive to TD.
> >
> > -John
>
> That theory is no longer operative. Current thinking is that TD is when the brain damage reaches a critical mass. There might be a case to be made for the treatment, but the fact remains that it does cause brain damage.
>
> S.Hi,
Can you please provide any links to studies that abort the old theory of TD? This must be relatively new data because all the information I have is mainly from the last 3 years or so and most of it points to the "old" theory.
In a brief summary if possible:
-What kind of neurotoxic transmission is thought
to cause the TD?-Why do the newer anti-psychotics with 5-ht2
antagonism have reduced TD given the old
theory is bunk?
I would really appreciate any information as this
is an important criteria in my medical decisions.Thanks,
John
Posted by steve on March 17, 2001, at 19:34:26
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » steve, posted by JohnX on March 17, 2001, at 7:20:02
This here explains how the hypersensitivity model simply doesn't explain reality-based observations. As it's ANCP it's blue ribbon and beyond reproach. It's not as strongly for the cell death model as other articles I've read but can't find, but it does suggest that the model is receiving more and more recognition.
http://www.acnp.org/G4/GN401000144/CH141.html
Essentially anytime dopamine is metabolized outside the neuron, as is caused by neuroleptics, it results in the release of byproducts that destroy cells in a way that is identical to how some scientists think cancer is caused.
As for why the socalled "atypicals" are less likely to cause the tardive syndromes, it's because they are usually given at doses that result in less dopamine receptor antagonist. Sort of like why a few rum and cokes a day doesn't cause as much damage as a gallon of vodka mixed with paint thinner a day.
Run a medline search for antipsychotics and volume, or look up some of the articles I've posted to the board in the past few months. Here's a link to a site that is strongly against any neuroleptic use, perhaps more so than I am. Be that as it may, the articles they cite from the likes of the Lancet are completely credible, and show how there is indisputably is substantial brain atrophy related with them. (The lancet is Britain's most prestigous medical journal.)
If you want to really make my day, ask your shrink how many free meals and other freebies he has accepted from neuroleptic peddlars. I think that you should know that to give truely "informed consent."
S.
> > >
> > > > I really don't think your shrink is doing you a favor by suggesting that TD is something one either has or doesn't have. TD is caused by the APDs killing neurons off, which they all do by their very mode of action. The only unknown is if it the neurotoxicity will suffice to inflict disabling neurological damage or not. A much better analogy would be say with lead poisoning, which some times does cause substantial CNS disturbacnes, and sometimes kills, but not always either.
> > > > > S.
> > >
> > >
> > > I thought TD was primarily caused by a lack of dopamine or blockade of D2 receptors spawning more D2 receptors? The inclusion of 5ht-2 antagonists in newer anti-psychotics was to increase the dopamine release in those receptors sensitive to TD.
> > >
> > > -John
> >
> > That theory is no longer operative. Current thinking is that TD is when the brain damage reaches a critical mass. There might be a case to be made for the treatment, but the fact remains that it does cause brain damage.
> >
> > S.
>
> Hi,
>
> Can you please provide any links to studies that abort the old theory of TD? This must be relatively new data because all the information I have is mainly from the last 3 years or so and most of it points to the "old" theory.
>
> In a brief summary if possible:
>
> -What kind of neurotoxic transmission is thought
> to cause the TD?
>
> -Why do the newer anti-psychotics with 5-ht2
> antagonism have reduced TD given the old
> theory is bunk?
>
> I would really appreciate any information as this
> is an important criteria in my medical decisions.
>
> Thanks,
> John
>
Posted by steve on March 18, 2001, at 2:05:08
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » steve, posted by JohnX on March 17, 2001, at 7:20:02
John,
The reason I suggested you ask about freebies, is not because I think they are totally illegitimate, but rather because I think they are abused.
There was a relatively recent article in my home town paper about how medical anonymity is totally gone. Pharmacies routinely sell info about who buys what from them. A psychiatrist was quoted as saying that one day a sales rep had walked into her office, and given her a list of her patients on competitor's drugs, and wanted to discuss why the patients couldn't be changed to their product, (which makes me think they were flogging the "atypicals".) Though that might be crass, the crassest part is that some companies adjust their freebies according to how much "product" they prescribe. I think this creates an enormous potential for conflict, and I think "consumers" should be aware of this.
S.
> > >
> > > > I really don't think your shrink is doing you a favor by suggesting that TD is something one either has or doesn't have. TD is caused by the APDs killing neurons off, which they all do by their very mode of action. The only unknown is if it the neurotoxicity will suffice to inflict disabling neurological damage or not. A much better analogy would be say with lead poisoning, which some times does cause substantial CNS disturbacnes, and sometimes kills, but not always either.
> > > > > S.
> > >
> > >
> > > I thought TD was primarily caused by a lack of dopamine or blockade of D2 receptors spawning more D2 receptors? The inclusion of 5ht-2 antagonists in newer anti-psychotics was to increase the dopamine release in those receptors sensitive to TD.
> > >
> > > -John
> >
> > That theory is no longer operative. Current thinking is that TD is when the brain damage reaches a critical mass. There might be a case to be made for the treatment, but the fact remains that it does cause brain damage.
> >
> > S.
>
> Hi,
>
> Can you please provide any links to studies that abort the old theory of TD? This must be relatively new data because all the information I have is mainly from the last 3 years or so and most of it points to the "old" theory.
>
> In a brief summary if possible:
>
> -What kind of neurotoxic transmission is thought
> to cause the TD?
>
> -Why do the newer anti-psychotics with 5-ht2
> antagonism have reduced TD given the old
> theory is bunk?
>
> I would really appreciate any information as this
> is an important criteria in my medical decisions.
>
> Thanks,
> John
>
Posted by SLS on March 19, 2001, at 18:12:44
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk?, posted by steve on March 16, 2001, at 3:51:38
Hi Steve.
I owe you an apology for my past reactions to your suggestion that neuroleptics produce brain damage by causing a shrinking of the brain. I am still dubious of this conclusions, as the data concerning reduction in brain mass remains equivocal. I don't think it serves well to state with certainty that brain shrinkage occurs. However, after reading the most recent threads regarding tardive dyskinesia, I feel that your characterization of its nature as being "brain damage" is justified. I hadn't realized the extent to which neurotoxic explanations for tardive dyskinesia (and perhaps schizophrenia itself) have developed.
I found the following two abstracts during a quick search on Medline for references to tardive dyskinesia and free radicals. Both studies suggest that the schizophrenia disorder itself may involve aberrant biological events that lead to the formation of abnormally high concentrations of damaging free radicals. I don't know if the experimental observations using these specific indices have been repeated. However, there may be a clinical observation that serves to cooraborate the results of the study. I recall that an abnormally high rate of idiopathic spontaneous dyskinesias occurs in schizophrenics who have not yet been exposed to medication. Investigators are searching for biological markers to determine which individuals are more succeptable to develop schizophrenia and TD. I read several studies that looked to identify alleles for specific enzyme polymorphisms that are believed to allow for increased levels of free radicals.
Sincerely,
Scott-----------------------------------------------------------------------
12: Prostaglandins Leukot Essent Fatty Acids 1996 Aug;55(1-2):33-43 Books,
LinkOut
Free radical pathology in schizophrenia: a review.Reddy RD, Yao JK
University of Pittsburgh Medical Center, Western Psychiatric Institute and
Clinic, PA 15213, USA.There is evidence that free radicals are involved in membrane pathology,
and may play a role in schizophrenia. Free radicals are reactive chemical
species generated during normal metabolic processes, and, in excess, can
damage lipids, proteins, and DNA. Regions of high oxygen consumption,
lipid content, and transition metals are at particular risk. Hence,
neuronal membranes are uniquely vulnerable to radical-mediated damage.
Elaborate antioxidant defense systems exist to protect against oxidative
stress. In schizophrenia there is evidence for dysregulation of free
radical metabolism, as detected by abnormal activities of critical
antioxidant enzymes and other indices of lipid peroxidation in plasma, red
blood cells, and cerebrospinal fluid. Such abnormalities have been
associated with tardive dyskinesia, negative symptoms, neurological signs,
poor premorbid function, and CT scan abnormalities. Studies to date have
generally been exploratory. Further elucidation of the role of free
radicals and antioxidants in schizophrenia and its treatment will require
systematic investigation.Publication Types:
Review
Review, tutorialPMID: 8888121
-----------------------------------------------------------------------
: Neuropsychopharmacology 2000 Aug;23(2):170-7 Books, LinkOut
Manganese superoxide dismutase gene polymorphism and schizophrenia:
relation to tardive dyskinesia.Hori H, Ohmori O, Shinkai T, Kojima H, Okano C, Suzuki T, Nakamura J
Department of Psychiatry, School of Medicine, University of Occupational
and Environmental Health, Kitakyushu, Japan.There has been increasing evidence that deranged superoxide dismutase
(SOD) activities might be a risk factor for schizophrenia and/or tardive
dyskinesia (TD). In the present study, we investigated the genetic
association between a functional polymorphism (Ala-9Val) in the human
manganese (Mn) SOD gene and schizophrenia or TD (192 schizophrenics: 39
with TD and 153 without TD; 141 controls). No significant differences in
the allelic or genotypic distribution between schizophrenics and controls
were observed. However, we did find a significant difference in genotypic
distribution between schizophrenics with and those without TD (p =. 03).
Moreover, decreased -9Ala (mutant) allele was found among patients with TD
(p =.02; odds ratio = 0.29; 95% confidence interval = 0.10-0.83). In
conjunction with previous findings of increased free radicals and
decreased SOD activities in TD subjects, these results suggest that the
-9Ala (high activity) MnSOD allele may play a role in protecting against
susceptibility to TD in schizophrenics.PMID: 10882843
Posted by steve on March 20, 2001, at 1:02:04
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » steve, posted by SLS on March 19, 2001, at 18:12:44
Thank you, thank you.
Isn't it sad that doctors don't tell you this, and that pharma companies aren't forced to label their "APDs" as neurotoxic?
If you want something to really chew on, you might like searching medline for free radicals, schizophrenia and melatonin. All studies of Melatonin in paranoid schizophrenics report that melatonin levels, are greatly below normal. Melatonin, as you may know, is one of the best chemicals to mop up free radicals. And at one time I believed that psychiatry is about solving "chemical imbalances." Now I believe it is about causing them and toxicities, as long as money can be made. And damn the patients.
S.
> Hi Steve.
>
> I owe you an apology for my past reactions to your suggestion that neuroleptics produce brain damage by causing a shrinking of the brain. I am still dubious of this conclusions, as the data concerning reduction in brain mass remains equivocal. I don't think it serves well to state with certainty that brain shrinkage occurs. However, after reading the most recent threads regarding tardive dyskinesia, I feel that your characterization of its nature as being "brain damage" is justified. I hadn't realized the extent to which neurotoxic explanations for tardive dyskinesia (and perhaps schizophrenia itself) have developed.
>
> I found the following two abstracts during a quick search on Medline for references to tardive dyskinesia and free radicals. Both studies suggest that the schizophrenia disorder itself may involve aberrant biological events that lead to the formation of abnormally high concentrations of damaging free radicals. I don't know if the experimental observations using these specific indices have been repeated. However, there may be a clinical observation that serves to cooraborate the results of the study. I recall that an abnormally high rate of idiopathic spontaneous dyskinesias occurs in schizophrenics who have not yet been exposed to medication. Investigators are searching for biological markers to determine which individuals are more succeptable to develop schizophrenia and TD. I read several studies that looked to identify alleles for specific enzyme polymorphisms that are believed to allow for increased levels of free radicals.
>
>
> Sincerely,
> Scott
>
> -----------------------------------------------------------------------
>
>
> 12: Prostaglandins Leukot Essent Fatty Acids 1996 Aug;55(1-2):33-43 Books,
> LinkOut
>
>
> Free radical pathology in schizophrenia: a review.
>
> Reddy RD, Yao JK
>
> University of Pittsburgh Medical Center, Western Psychiatric Institute and
> Clinic, PA 15213, USA.
>
> There is evidence that free radicals are involved in membrane pathology,
> and may play a role in schizophrenia. Free radicals are reactive chemical
> species generated during normal metabolic processes, and, in excess, can
> damage lipids, proteins, and DNA. Regions of high oxygen consumption,
> lipid content, and transition metals are at particular risk. Hence,
> neuronal membranes are uniquely vulnerable to radical-mediated damage.
> Elaborate antioxidant defense systems exist to protect against oxidative
> stress. In schizophrenia there is evidence for dysregulation of free
> radical metabolism, as detected by abnormal activities of critical
> antioxidant enzymes and other indices of lipid peroxidation in plasma, red
> blood cells, and cerebrospinal fluid. Such abnormalities have been
> associated with tardive dyskinesia, negative symptoms, neurological signs,
> poor premorbid function, and CT scan abnormalities. Studies to date have
> generally been exploratory. Further elucidation of the role of free
> radicals and antioxidants in schizophrenia and its treatment will require
> systematic investigation.
>
> Publication Types:
> Review
> Review, tutorial
>
> PMID: 8888121
>
> -----------------------------------------------------------------------
>
>
> : Neuropsychopharmacology 2000 Aug;23(2):170-7 Books, LinkOut
>
>
> Manganese superoxide dismutase gene polymorphism and schizophrenia:
> relation to tardive dyskinesia.
>
> Hori H, Ohmori O, Shinkai T, Kojima H, Okano C, Suzuki T, Nakamura J
>
> Department of Psychiatry, School of Medicine, University of Occupational
> and Environmental Health, Kitakyushu, Japan.
>
> There has been increasing evidence that deranged superoxide dismutase
> (SOD) activities might be a risk factor for schizophrenia and/or tardive
> dyskinesia (TD). In the present study, we investigated the genetic
> association between a functional polymorphism (Ala-9Val) in the human
> manganese (Mn) SOD gene and schizophrenia or TD (192 schizophrenics: 39
> with TD and 153 without TD; 141 controls). No significant differences in
> the allelic or genotypic distribution between schizophrenics and controls
> were observed. However, we did find a significant difference in genotypic
> distribution between schizophrenics with and those without TD (p =. 03).
> Moreover, decreased -9Ala (mutant) allele was found among patients with TD
> (p =.02; odds ratio = 0.29; 95% confidence interval = 0.10-0.83). In
> conjunction with previous findings of increased free radicals and
> decreased SOD activities in TD subjects, these results suggest that the
> -9Ala (high activity) MnSOD allele may play a role in protecting against
> susceptibility to TD in schizophrenics.
>
> PMID: 10882843
Posted by SLS on March 20, 2001, at 7:44:50
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » SLS, posted by steve on March 20, 2001, at 1:02:04
Steve,
> Isn't it sad that doctors don't tell you this, and that pharma companies aren't forced to label their "APDs" as neurotoxic?
Well, I don't think there is sufficient evidence yet to even use the word "putative" to describe as neurodegenative the acknowledged and usually irreversible side effects of neuroleptic antipsychotics. Tardive dyskinesias, tardive dystonias, and tardive akathisia are recognized as severe consequences of treatment with APs in a sizeable percentage of people (I don't know the statistics).
Severe schizophrenia is a hideous derangement of humanity. I deem it unacceptable to withhold an almost magically effective treatment that brings these people back into our world of coherency. (I don't think it would serve schizophrenia well to begin an esoteric debate regarding the coherency of the world at this point). I also deem it unacceptable to withhold information from everyone concerned and unconcerned regarding the full nature of the possible severe reactions that can occur. Likewise, it would irresponsible not to describe the remedial treatments available to address them. For those who must make a decision, it becomes a risk/consequence versus benefit judgment. Unfortunately, I am unaware of treatments that are more efficacious than the neuroleptic antipsychotics, the atypicals probably representing acceptably effective treatment.
The problem: If not these drugs, than which?
What treatments do you think deserve consideration?
Temorary solution?: Begin a prophylactic treatment simultaneously with the initiation of the antipsychotic to minimize or prevent tardive dyskinesia. From what I have encountered in the medical literature, the issue of neurotoxic processes are being intensively studied from the perspective of both pure neuroscience research and clinical application to specific medical conditions including Alzheimer's Dementia, Parkinson's Disease, Huntington's Chorea, schizophrenia, and "recreational" drugs like methamphetamine. It might not be too far off that this type of temporary solution becomes applicable.
What do you think?
One thought I had is to reduce the rate at which neurons synthesize dopamine, since this might be a primary pathway toward the evolution of neurotoxic substances. MAO inhibitors like selegiline? Dopamine agonists like bromocriptine or Mirapex? COMT inhibitors? With an antipsychotic on board, perhaps any potential for these drugs to be psychotogenic would be greatly reduced or made nul. I would be curious to learn if combining an atypical neuroleptic with relatively low affinity for DA receptors with a DA agonist produces psychosis or exacerbates schizoid symptoms. I would be curious to see what Mirapex would do, only because it seems to be the focus of much study as a substance which prevents neurotoxic damage. My concern here is that Mirapex might carry a greater liability than the other DA agonists to produce psychosis because it stimulates D3 receptors in brain structures above the striatum that might be involved in producing positive schizophrenic symptoms. The stimulation of D3 receptors would not be countered because neuroleptic antipsychotics can't block them. I don't know enough at this point about all of the locations of D3 receptors and their contribution to schizoid or otherwise psychotic conditions.
- Scott
Posted by Anna P. on March 20, 2001, at 12:38:02
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk?, posted by SLS on March 20, 2001, at 7:44:50
> I don't respond any more to drugs. Geodon was my hope. I have it already, but I'm scared to try it. I've read the medical insert that lists not only the increase in QTc interval, heart beat increase, tardive diskinesia and sudden death.
Anna P.
Posted by Chris A. on March 20, 2001, at 14:06:54
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » ShelliR, posted by Chris A. on March 14, 2001, at 21:35:42
It scares me spitless - all this talk about possible neuron death, increase of fee radicals etc., etc. with neuroleptics. It is down right depressing since I was hoping ziprasidone would help (something or someone needs to help - soon). Since I found out for sure in Jan that I have sustained right hemisphere damage my anxiety is understandably skyrocketing over this. I am afriad to increase the dose of the Geodon out of fear. I'm afraid almost to take it at all. Thanks Scott, for your words of moderation and encouragement. They are badly needed. I really wish we could get to the bottom of this, but I don't think anyone really knows.
Blessings,
Chris A.
Posted by KarenB on March 20, 2001, at 14:15:07
In reply to Re: I'm scared to try Geodon..., posted by Anna P. on March 20, 2001, at 12:38:02
> > I don't respond any more to drugs. Geodon was my hope. I have it already, but I'm scared to try it. I've read the medical insert that lists not only the increase in QTc interval, heart beat increase, tardive diskinesia and sudden death.
>
> Anna P.Anna,
My thoughts are that I would much prefer sudden death to the slower, more agonizing variety that is mine with my illness left untreated. I am trialing Geodon now and it is working well for me at 40mg am & pm.
My understanding is that Geodon has much less chance of causing TD than the older, typical APs. MUCH, MUCH less, I am hoping.
I am not saying that I want to remain completely ignorant, however, I could spend hours and days reading studies to terrify myself into being afraid to take anything that would actually give me a life. I will choose for now to stay at a relatively low dose and pray for the best. I will also continue my use of Melatonin, which I did not realize has benefits other than helping me sleep. Cool. Thanks for that, Scott. BTW, what exactly IS a QTc interval, anyway?
Karen
Posted by Sunnely on March 20, 2001, at 20:11:08
In reply to Re: I'm scared to try Geodon..., posted by Anna P. on March 20, 2001, at 12:38:02
Prolonged QTc is the time it takes for the electrical system of the heart to repolarize. It is measured in msec (milliseconds). Between 350-440 msec is normal; between 450-500 msec is a potential concern; longer than 500 msec poses increased risk of arrhythmias (heart beat irregularities). Prolonged QTc can be a harbinger to a more serious heart beat irregularity called "torsades."
If you do not belong in the following groups of people, your fear of using Geodon is most likely unwarranted:
1. People with congenital long QT syndrome. Some people are born with this heart condition. Geodon is contraindicated in people with this condition. If you have had episodes of palpitations and syncope (passing out), you need to have a heart work up (evaluation) to rule out this possibility.
2. People who take drugs known to prolong QTc. Example of these drugs are (not a complete list) terfenadine (Seldane), astemizole (Hismanal), cisapride (Propulsid), pimozide (Orap), thioridazine (Mellaril), quinidine (Quinaglute), sotalol (Betapace), sparfloxacin (Zagam). The first 3 drugs above are no longer available in the US market. Your doctor and/or pharmacist should ask you if you are taking other drugs (especially those with potential to prolong QTc) before prescribing you Geodon. If they don't ask you, make sure you volunteer this information.
3. People with recent heart attack, those with uncompensated heart failure, and those with known history of heart arrhythmias should not take Geodon.
4. People with hypokalemia (low potassium level). If you are taking a diuretic (water pill), your potassium level should be regularly checked and if low, potassium supplement should be given. Low potassium makes the heart more irritable and prone to heart beat irregularity including prolonged QTc and possible serious heart beat irregularity. People with active eating disorders (anorexia and bulimia) may also be at risk for low potassium level. (Abuse of laxatives not uncommon with these people.) For these people, electrolytes (includes potassium) should be checked before starting Geodon.
5. People with hypomagnesemia (low magnesium level). Seen more especially with the active alcoholics. Electrolytes including potassium and magnesium should be checked first before starting Geodon on these people.
6. People who recently overdosed on tricyclic antidepressants. Electrocardiogram should be monitored and make certain they are free of prolongation of QTc before starting Geodon. Better yet, if antipsychotic drug is needed, try a different one.
To go back in time, ziprasidone (originally named Zeldox), was submitted for FDA approval in March 1997. However, Pfizer, the manufacturer, received notification from the US FDA in the summer of 1998 indicating that approval of ziprasidone would be delayed. The primary reason for this non-approval was apparently safety concerns related to potential heart side effects, specifically prolongation of the QTc interval, which has become a controversial issue for new antipsychotics. Pfizer collected more data and did more studies regarding its safety. Pfizer conducted further clinical trials pitting ziprasidone against haloperidol (Haldol), olanzapine (Zyprexa), risperidone (Risperdal), and quetiapine (Seroquel). The heart effects of each of the drugs were measured and monitored at optimum doses. Each drug was then compared with thioridazine (Mellaril), the older antipsychotic known to exhibit the strongest effect on QTc interval and now designated by FDA as a second-line drug due to its strong potential for heart arrhythmias.
The study revealed that the prolonging effect on QTc interval for ziprasidone was indeed longer than the four comparison atypical antipsychotics, but was much shorter than that seen with thioridazine. As a result, the approved labeling for ziprasidone includes extensive language warning of the theoretical potential for the drug to cause heart arrhythmias.
After nearly 4 years, Pfizer was able to convince the FDA that ziprasidone offered sufficient enough benefits for patients with schizophrenia to outweigh its potential for serious side effects. (Note: The FDA declined to approve Pfizer's original trade name, Zeldox, because of, it said, "similarities in spelling or pronunciation which may cause confusion with the proprietary name or the established name of a different drug or ingredient." The FDA was concerned about similarities between Zeldox and two other medications, Zyvox, Pharmacia & Upjohn's latest high-powered antibiotic, and Zoladex, a chemotherapeutic drug for prostate cancer made by AztraZeneca. The FDA approved Pfizer's request to use the trade name Geodon, pronounced gee-oh-don, instead of Zeldox.)
On the bright side, one big advantage of ziprasidone over the other atypical antipsychotics is its less propensity to cause weight gain. In fact, the drug appears to be "weight neutral." This is significantly different from its fellow antipsychotics' tendency to induce often significant gains in a patient's weight. Weight gain has long been considered a barrier to patient compliance with antipsychotic medications.
Another potential advantage of ziprasidone over its antipsychotic counterparts is its less propensity to cause elevations of cholesterol. Total cholesterol, LDL cholesterol (bad cholesterol), HDL cholesterol (good cholesterol), and triglyceride levels are important predictors of cardiovascular disease risk. In contrast to the other atypical antipsychotics and Mellaril, in a clinical trial, the ziprasidone group demonstrated marked median decreases from baseline in total cholesterol and LDL cholesterol, with no impact on HDL cholesterol. In recent clinical studies, it was consistently demonstrated that weight gain is associated with increased in blood sugar (diabetes) and triglyceride levels. Among the atypical antipsychotics, Clozaril and Zyprexa are more commonly linked to significant weight gain, diabetes, and elevations of triglycerides.
Although we need more time to determine its real risk, Geodon, just like the other atypical antipsychotics, probably has low risk for tardive dyskinesia (TD). Of course, some people are more prone to develop TD than others. The highest risk are the elderly people and those with concurrent neurological conditions or brain diseases. Again, time will tell.
+++++++++++++++++++++++++++++++++++++++> > I don't respond any more to drugs. Geodon was my hope. I have it already, but I'm scared to try it. I've read the medical insert that lists not only the increase in QTc interval, heart beat increase, tardive diskinesia and sudden death.
>
> Anna P.
Posted by Lexie on March 20, 2001, at 23:20:23
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » steve, posted by SLS on March 19, 2001, at 18:12:44
> Hi Steve.
>
> I owe you an apology for my past reactions to your suggestion that neuroleptics produce brain damage by causing a shrinking of the brain. I am still dubious of this conclusions, as the data concerning reduction in brain mass remains equivocal. I don't think it serves well to state with certainty that brain shrinkage occurs. However, after reading the most recent threads regarding tardive dyskinesia, I feel that your characterization of its nature as being "brain damage" is justified. I hadn't realized the extent to which neurotoxic explanations for tardive dyskinesia (and perhaps schizophrenia itself) have developed.
>
> I found the following two abstracts during a quick search on Medline for references to tardive dyskinesia and free radicals. Both studies suggest that the schizophrenia disorder itself may involve aberrant biological events that lead to the formation of abnormally high concentrations of damaging free radicals. I don't know if the experimental observations using these specific indices have been repeated. However, there may be a clinical observation that serves to cooraborate the results of the study. I recall that an abnormally high rate of idiopathic spontaneous dyskinesias occurs in schizophrenics who have not yet been exposed to medication. Investigators are searching for biological markers to determine which individuals are more succeptable to develop schizophrenia and TD. I read several studies that looked to identify alleles for specific enzyme polymorphisms that are believed to allow for increased levels of free radicals.
>
>
> Sincerely,
> Scott
>
> -----------------------------------------------------------------------
>
>
> 12: Prostaglandins Leukot Essent Fatty Acids 1996 Aug;55(1-2):33-43 Books,
> LinkOut
>
>
> Free radical pathology in schizophrenia: a review.
>
> Reddy RD, Yao JK
>
> University of Pittsburgh Medical Center, Western Psychiatric Institute and
> Clinic, PA 15213, USA.
>
> There is evidence that free radicals are involved in membrane pathology,
> and may play a role in schizophrenia. Free radicals are reactive chemical
> species generated during normal metabolic processes, and, in excess, can
> damage lipids, proteins, and DNA. Regions of high oxygen consumption,
> lipid content, and transition metals are at particular risk. Hence,
> neuronal membranes are uniquely vulnerable to radical-mediated damage.
> Elaborate antioxidant defense systems exist to protect against oxidative
> stress. In schizophrenia there is evidence for dysregulation of free
> radical metabolism, as detected by abnormal activities of critical
> antioxidant enzymes and other indices of lipid peroxidation in plasma, red
> blood cells, and cerebrospinal fluid. Such abnormalities have been
> associated with tardive dyskinesia, negative symptoms, neurological signs,
> poor premorbid function, and CT scan abnormalities. Studies to date have
> generally been exploratory. Further elucidation of the role of free
> radicals and antioxidants in schizophrenia and its treatment will require
> systematic investigation.
>
> Publication Types:
> Review
> Review, tutorial
>
> PMID: 8888121
>
> -----------------------------------------------------------------------
>
>
> : Neuropsychopharmacology 2000 Aug;23(2):170-7 Books, LinkOut
>
>
> Manganese superoxide dismutase gene polymorphism and schizophrenia:
> relation to tardive dyskinesia.
>
> Hori H, Ohmori O, Shinkai T, Kojima H, Okano C, Suzuki T, Nakamura J
>
> Department of Psychiatry, School of Medicine, University of Occupational
> and Environmental Health, Kitakyushu, Japan.
>
> There has been increasing evidence that deranged superoxide dismutase
> (SOD) activities might be a risk factor for schizophrenia and/or tardive
> dyskinesia (TD). In the present study, we investigated the genetic
> association between a functional polymorphism (Ala-9Val) in the human
> manganese (Mn) SOD gene and schizophrenia or TD (192 schizophrenics: 39
> with TD and 153 without TD; 141 controls). No significant differences in
> the allelic or genotypic distribution between schizophrenics and controls
> were observed. However, we did find a significant difference in genotypic
> distribution between schizophrenics with and those without TD (p =. 03).
> Moreover, decreased -9Ala (mutant) allele was found among patients with TD
> (p =.02; odds ratio = 0.29; 95% confidence interval = 0.10-0.83). In
> conjunction with previous findings of increased free radicals and
> decreased SOD activities in TD subjects, these results suggest that the
> -9Ala (high activity) MnSOD allele may play a role in protecting against
> susceptibility to TD in schizophrenics.
>
> PMID: 10882843Are you for real? My doctor just took me off Lamictal and put me on Geodon for Bipolar 2, I am sure you were sharing some interesting information, but I didn't understand I have been out of the loop for a few months if you will excuse my ignorance and humor me with me with me a "undergraduate" explaination it would be apreciated.
Posted by KarenB on March 20, 2001, at 23:35:10
In reply to Re: I'm scared to try Geodon... » Anna P., posted by Sunnely on March 20, 2001, at 20:11:08
Sunnely,
Wow, thanks for all that great information - and in language I can understand. You're the best, man...wait a minute - you are a man, right(?) Now I'm not at all sure why I think that:)
Karen
Posted by steve on March 21, 2001, at 0:15:20
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk?, posted by SLS on March 20, 2001, at 7:44:50
I think we agree on everything. People should make * informed * choices. If they feel that APDs help, let them take it, but not in a state of ignorance to the risks.
I would like to see Dr. Mosher's work www.moshersoteria.com be further investigated. He was a division chief at the NIMH until he claimed there were alternatives to APDs for crying out loud.
I would also like to see some investigation of the pineal gland in schizophrenia and severe bipolar disorder. Since psychiatry is supposedly about chemical imbalances, and there are reports of pineal related chemical imbalances, it would seem to me that that would be worth looking into.
S.
> Steve,
>
> > Isn't it sad that doctors don't tell you this, and that pharma companies aren't forced to label their "APDs" as neurotoxic?
>
> Well, I don't think there is sufficient evidence yet to even use the word "putative" to describe as neurodegenative the acknowledged and usually irreversible side effects of neuroleptic antipsychotics. Tardive dyskinesias, tardive dystonias, and tardive akathisia are recognized as severe consequences of treatment with APs in a sizeable percentage of people (I don't know the statistics).
>
> Severe schizophrenia is a hideous derangement of humanity. I deem it unacceptable to withhold an almost magically effective treatment that brings these people back into our world of coherency. (I don't think it would serve schizophrenia well to begin an esoteric debate regarding the coherency of the world at this point). I also deem it unacceptable to withhold information from everyone concerned and unconcerned regarding the full nature of the possible severe reactions that can occur. Likewise, it would irresponsible not to describe the remedial treatments available to address them. For those who must make a decision, it becomes a risk/consequence versus benefit judgment. Unfortunately, I am unaware of treatments that are more efficacious than the neuroleptic antipsychotics, the atypicals probably representing acceptably effective treatment.
>
> The problem: If not these drugs, than which?
>
> What treatments do you think deserve consideration?
>
> Temorary solution?: Begin a prophylactic treatment simultaneously with the initiation of the antipsychotic to minimize or prevent tardive dyskinesia. From what I have encountered in the medical literature, the issue of neurotoxic processes are being intensively studied from the perspective of both pure neuroscience research and clinical application to specific medical conditions including Alzheimer's Dementia, Parkinson's Disease, Huntington's Chorea, schizophrenia, and "recreational" drugs like methamphetamine. It might not be too far off that this type of temporary solution becomes applicable.
>
> What do you think?
>
> One thought I had is to reduce the rate at which neurons synthesize dopamine, since this might be a primary pathway toward the evolution of neurotoxic substances. MAO inhibitors like selegiline? Dopamine agonists like bromocriptine or Mirapex? COMT inhibitors? With an antipsychotic on board, perhaps any potential for these drugs to be psychotogenic would be greatly reduced or made nul. I would be curious to learn if combining an atypical neuroleptic with relatively low affinity for DA receptors with a DA agonist produces psychosis or exacerbates schizoid symptoms. I would be curious to see what Mirapex would do, only because it seems to be the focus of much study as a substance which prevents neurotoxic damage. My concern here is that Mirapex might carry a greater liability than the other DA agonists to produce psychosis because it stimulates D3 receptors in brain structures above the striatum that might be involved in producing positive schizophrenic symptoms. The stimulation of D3 receptors would not be countered because neuroleptic antipsychotics can't block them. I don't know enough at this point about all of the locations of D3 receptors and their contribution to schizoid or otherwise psychotic conditions.
>
>
> - Scott
Posted by SLS on March 21, 2001, at 7:47:53
In reply to Re: I'm scared to try Geodon..., posted by KarenB on March 20, 2001, at 14:15:07
I don't know if it has been stated in this thread but...
At the LOW DOSAGES that these neuroleptic antipsychotics are to be used for depression, bipolar disorder, and other non-schizoid conditions, the risk of developing EPS and tardive dyskinesia is MUCH lower. Of course, I would not want to portray this as zero risk. However, right now, I myself have no hesitency to use low-dosage APs as I have already progressed through trials of Zyprexa, Seroquel, and Risperdal.I hope this adds some perspective to this issue.
** KAREN! GOOD LUCK WITH GEODON!I will be awaiting your observations and conclusions with great excitement.
- Scott
Posted by Anna P. on March 21, 2001, at 11:21:58
In reply to Re: I'm scared to try Geodon..., posted by KarenB on March 20, 2001, at 14:15:07
> > > I don't respond any more to drugs. Geodon was my hope. I have it already, but I'm scared to try it. I've read the medical insert that lists not only the increase in QTc interval, heart beat increase, tardive diskinesia and sudden death.
> >
> > Anna P.
>
> Anna,
>
> My thoughts are that I would much prefer sudden death to the slower, more agonizing variety that is mine with my illness left untreated. I am trialing Geodon now and it is working well for me at 40mg am & pm.
>
> My understanding is that Geodon has much less chance of causing TD than the older, typical APs. MUCH, MUCH less, I am hoping.
>
> I am not saying that I want to remain completely ignorant, however, I could spend hours and days reading studies to terrify myself into being afraid to take anything that would actually give me a life. I will choose for now to stay at a relatively low dose and pray for the best. I will also continue my use of Melatonin, which I did not realize has benefits other than helping me sleep. Cool. Thanks for that, Scott. BTW, what exactly IS a QTc interval, anyway?
>
> Karen
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