Psycho-Babble Medication Thread 526838

Shown: posts 1 to 14 of 14. This is the beginning of the thread.

 

schitsophrenia NMDA and lithium

Posted by linkadge on July 12, 2005, at 18:11:38

I read an article that suggested that schitsophrenia might be caused by low activity of NMDA. It suggested that ketamine and PCP were able to elicit psychosis because they were NMDA antagonists.

Why then, is lithium, an NMDA antagonist often used in schitsophrenia ?


Linkadge

 

Re: schitsophrenia NMDA and lithium

Posted by SLS on July 12, 2005, at 18:51:27

In reply to schitsophrenia NMDA and lithium, posted by linkadge on July 12, 2005, at 18:11:38

> I read an article that suggested that schitsophrenia might be caused by low activity of NMDA. It suggested that ketamine and PCP were able to elicit psychosis because they were NMDA antagonists.
>
> Why then, is lithium, an NMDA antagonist often used in schitsophrenia ?

I must be missing out on the current treatments of schizophrenia. I thought lithium was of little value unless the actual disorder was schizoaffective. I'll peruse Medline and see what's happening with lithium and schizoid disorders. It's possible that the degree to which lithium interacts with NMDA receptors is small enough to be negligible.


- Scott

 

Re: schitsophrenia NMDA and lithium

Posted by linkadge on July 12, 2005, at 19:17:39

In reply to Re: schitsophrenia NMDA and lithium, posted by SLS on July 12, 2005, at 18:51:27

Really ? I thought that lithium, like magnesium and zinc were very potent NMDA antagonists.

Linkadge

 

Re: schitsophrenia NMDA and lithium

Posted by linkadge on July 12, 2005, at 19:26:52

In reply to Re: schitsophrenia NMDA and lithium, posted by linkadge on July 12, 2005, at 19:17:39

I did some more searching and it does seem that you are right in that schitsophrenia doesn't seem to respond well to lithium alone.


Linkadge

 

Re: schitsophrenia NMDA and lithium » linkadge

Posted by Shawn. T. on July 12, 2005, at 19:41:14

In reply to Re: schitsophrenia NMDA and lithium, posted by linkadge on July 12, 2005, at 19:17:39

Lithium indirectly inhibits NMDA mediated calcium influx. It isn't an NMDA antagonist.

Shawn

 

Re: schitsophrenia NMDA and lithium

Posted by linkadge on July 12, 2005, at 20:10:02

In reply to Re: schitsophrenia NMDA and lithium » linkadge, posted by Shawn. T. on July 12, 2005, at 19:41:14

Am I correct in saying that Zinc, and Magnesium are NMDA agaonists?

Many studies that I have been reading refer to zinc and magnesium as "potent NMDA antagonists"

Linkadge

 

Re: schitsophrenia NMDA and lithium

Posted by med_empowered on July 13, 2005, at 1:07:03

In reply to Re: schitsophrenia NMDA and lithium, posted by linkadge on July 12, 2005, at 20:10:02

hey! The line between schizoaffective and schizophrenia is blurry at best; if you look at most studies, schizoaffective people are lumped in with those with schizophrenia. Interestingly enough, although lithium and other mood-stabilizers are commonly used along with antipsychotics and/or antidepressants in treating schizoaffective disorder, these combinations have **not** been very well studied, and the results in many studies are kind of mixed...lithium, in particular, sometimes helps, but can also do bad things when mixed with neuroleptics..it tends to increase the risk of neuroleptic malignancy syndrome and, when combined with Haldol (and I beleive some other old-school phenothiazines as well), it can cause a form of permanent brain damage similar to that seen after encephalitis lethargica (neuroleptics alone can produce changes in the brain that are similar to those seen with this disorder; they also often induce so-called "pseudo-Parkinson's" which is just like normal Parkinson's, except the effect is drug-induced and usually reversible upon termination of the medication or lowering of the dosage). Anyway, mood-stabilizers are used for those with schizoaffective disorder on a regular basis, and they are also employed a good bit in those with schizophrenia; the idea seems to be that using lithium, depakote, or the like allows the dosage of the neuroleptic to be lowered substantially (this is similar to the strategy some use in using long-term, medium-to-high dose benzodiazpenes to augment antipsychotics). My personal take on all this is that treatment for most disorders, but especially schizophrenia/schizoaffective disorders, is fundamentally flawed and unimpressive. According to one study I read, the "improvements" in the lives of those with schizophrenia peaked in the 1970s; at best, those with schizophrenia are about as well off as they were in the early 1900s in terms of lifespan, productivity, suicide rates, etc. When you factor in up-front drug/hospitaliaztion costs and the ill-effects of long-term antipsychotic administration, one could argue that those with schizophrenia were better served in the days of hydrotherapy and Quaker-inspired "moral treatment" (which, by the way, was awfully expensive, but seems to have been reasonably effective and benign in terms of potential side-effects). One interesting study--I'll look up the author name, title, etc.--did a head-to-head comparison of antipsychotics and benzodiazpenes in managing the "acute" phase of schizophrenia, the first 4 weeks following an episode leading to hospitalization. These first weeks are usually the hardest in terms of treatment. Anyway, the study found that there were no major differences in efficacy between those who were simply given Valium and those who were given neuroleptics (I believe that this study used atypical neuroleptics as treatment for those in the antipsychotic group, but I'm not quite sure). It would appear that, when one factors in up-front medication costs, patient compliance/non-compliance, and the costs associated with undesirable side-effects (rehospitalization, additional medications, the costs associated with constant "med management") those treated with benzodiazepenes actually received more efficient, well-tolerated treatment than those treated with neuroleptics. And, of course, the famous World Health Organization studies found that many people diagnosed with schizophrenia (based on accepted international guidelines, not necessarily the DSM) actually were more likely to recover in poor nations with strong social support systems than those who lived in welathier, industrial/post-industrial nations that encouraged the long-term use of neuroleptics. In those countries, a majority of people recovered from schizophrenia without the prolonged use of neuroleptics; in the united states and many european countries, it appeared that the vast majority did not recover even with the use of neuroleptics. "Recovery" was measured by rehospitalization, symptom relapse, and, most importantly, long-term disability and economic functioning.

 

Re: schitsophrenia NMDA and lithium

Posted by linkadge on July 13, 2005, at 6:28:36

In reply to Re: schitsophrenia NMDA and lithium, posted by med_empowered on July 13, 2005, at 1:07:03

I know it was mentioned before, but I felt totally lied to when I found out that John Nash rarely used AP's. The movie tried to do mental illness justice but by lying makes things considerably worse.

One study being done is looking at weather lithium can prevent the occuance of schitsophrenia in so called "susceptable individuals"

Linkadge

 

Re: schitsophrenia NMDA and lithium » med_empowered

Posted by linkadge on July 13, 2005, at 6:34:26

In reply to Re: schitsophrenia NMDA and lithium, posted by med_empowered on July 13, 2005, at 1:07:03

What do you think is the main cause of schitsohprenia. I think the dopamine hypothesis is a little weak. I think it might be a collection of structural abnormalities that lead to a some sort of global dysfunction ?

AP's always made me feel psychotic.


Linkadge

 

Re: schitsophrenia NMDA and lithium » med_empowered

Posted by SLS on July 13, 2005, at 11:07:41

In reply to Re: schitsophrenia NMDA and lithium, posted by med_empowered on July 13, 2005, at 1:07:03

> The line between schizoaffective and schizophrenia is blurry at best;


No way!

Sorry to disagree with you on this one.

They are two different beasts entirely. Schizoaffective disorder is more than simply a comorbid occurence of schizophrenia and bipolar disorder.

The differential diagnosis is easy to make, especially if you can get any sort of life-chart assembled through careful interview of patient and family. Otherwise, the syndrome must be followed prospectively. The description of schizoaffective disorder can be found here:

http://www.mentalhealth.com/dis1/p21-ps05.html

Unfortunately, this description makes no mention of whether these symptoms appear in any particular order. I believe that they do.

I was able to observe very closely the progression of schizoaffective disorder as it manifested in a friend of mine. I also come in contact with several people who have schizophrenia. I am able to see the difference easily without needing special training. The thought disorder of schizophrenia is not accompanied by a variability in affect and tends to remain stable without intervention.

I observed the order and character of the changes and overlap in mental state seen in my friend's presentation of schizoaffective disorder were predictable and obvious:

Euthymia -> anxiety / hypomania / insomnia -> manic psychosis / delusions -> schizoid thought disorder / hallucinations -> depression -> euthymia -> etc.

For what it's worth, I worked as a research assistant to Baron Shopsin, MD, one of the first to identify the schizoaffective presentation as a separate disorder. He authored several books on the subject. This was as early as 1983.


- Scott

 

Re: schitsophrenia NMDA and lithium » linkadge

Posted by ed_uk on July 13, 2005, at 14:13:23

In reply to Re: schitsophrenia NMDA and lithium » med_empowered, posted by linkadge on July 13, 2005, at 6:34:26

>AP's always made me feel psychotic.

In what way?

APs seem to block my thoughts, I just can't think normally.....this makes me panic. Even the simplest tasks were impossible, APs make me completely helpless, I can't do anything for myslelf, simply opening a door would be a challenge. A moderate dose of chlorpromazine (Thorazine) produced a feeling of intense panic and a sensation of impending doom + severe akathisia. Very low doses just made me dumb and slightly aggravated my anxiety.

~Ed

 

Re: schitsophrenia NMDA and lithium

Posted by linkadge on July 13, 2005, at 17:40:02

In reply to Re: schitsophrenia NMDA and lithium » linkadge, posted by ed_uk on July 13, 2005, at 14:13:23

Thats exactly it. I don't wish an AP on anybody. I have many of the same feelings you have had. Like a feeling of utter worthlessness. I too experience panic on them because I start to doubt anything I can do.


I read an article of a psychitrist that had practiced for many years believing that AP's were God's gift to Schitsophrenia. She took one one day, and because of how she felt she had a nervous breakdown. The med itself didn't induce the breakdown, rather it was notion that she had been liberally prescribing these meds with such confidence without knowing just how negativly they could influence the patient's life.


Linkadge

 

Re: schitsophrenia NMDA and lithium

Posted by jparsell82 on July 14, 2005, at 13:17:32

In reply to Re: schitsophrenia NMDA and lithium, posted by linkadge on July 13, 2005, at 17:40:02

I don't believe that APs are bad. I think they're just not advanced enough yet to accurately correct any problem. Like with dopamine, they target various receptors. Some of these might need blocked and some of them might not. Or they might need blocked in a certain part of the brain but not another. Such as the drug Sertindole that blocks D2 receptors in the limbic system but not in the striatum, a unique action compared to other APs. Supposedly, it's supposed to have a reported anxiolytic profile without sedation. Who knows? And then we have partial agonists now, and glutamate modulators being studied.

I guess what I'm saying is, I don't care for any of the current APs myself. But, they are getting better as they get more selective and more research is done.

 

Re: schitsophrenia NMDA and lithium

Posted by linkadge on July 14, 2005, at 16:05:45

In reply to Re: schitsophrenia NMDA and lithium, posted by jparsell82 on July 14, 2005, at 13:17:32

Its the same with AD's. I don't think the idea of an antidepressant is bad. But I do think that we don't have any good ones.


Linkadge


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