Posted by SLS on March 17, 2006, at 12:00:02
In reply to Re: Never thought I'd hear this....., posted by linkadge on March 17, 2006, at 9:55:15
> > My point is this: The cluster of behaviors that >we see with the administration of amphetamine, >and that you have listed, is not a sufficient >criterion for true mania such that these >investigators needed to find other models to use.
> Some of the models we have today may not be conclusive, but I don't think that is reason to ignore them.
The only thing these models demonstrate is that psychostimulants can produce in animals the same behaviors that they produce in man. My belief (currently) is that what psychostimulants produce in a healthy (not bipolar) man is not mania. Neither do antidepressants produce these behaviors in animals. They only produce them in man in association with affective disorder. There are probably exceptions, of course. I contend that the majority of antidepressant-induced manias are those produced in people whom have a bipolar disorder and not a unipolar disorder. The citations you produced links to seem to support this. Unfortunately no single study was designed to test the specific question that we are debating: Does an antidepressant-induced mania usually indicate bipolar disorder, despite a lack of previous spontaneous episodes?
> > They judged the validity of their models based >upon the capacity of mood stabilizers to reverse >them. The hyperlocomotive and hyperlibidinal >effects produced by psychostimulants are thus >not equivalent to mania, and the presence of >these behaviors is not sufficient to presume a >valid animal model.
> Psychosis and mania have been effectively treated with drugs that were active in these paradigms.
Yes, but they are also active in models of schizophrenic psychosis. They don't seem to me to be specific for mania. Despite this, I will concede that it is possible to "light up" the manic areas of the brain in a healthy individual if, as Dr. Manji said, the conditions are right. The key question is, what are these conditions? Does using an SSRI as monotherapy qualify? That is what we are talking about here, as we are also talking about numbers. What is the percentage of people whom experience mania as a reaction to an SSRI that are bipolar? How do we determine this? Again, I think this issue can be resolved by performing a longitudinal study of people whom have had this reaction using life charting and prospective observation. At this time, I would argue that if there are other features of bipolarity present (including family history), then a manic reaction to an antidepressant indicates treating the person as if they were bipolar. I believe the chances of getting them well is enhanced by doing so.
> We can aruge that these behaviors aren't identical to human mania, but we could argue the same thing for rodent depression. That doesn't negate the fact that the model is oftentimes highly predictive of drug sucess in humans.
Definitely. But does that answer the clinical questions being pursued here?
> > Otherwise, I imagine they would have used >cocaine. So far, I don't believe that they have >been able to reproduce mania in rodents using >SSRIs.
> I don't know.
> > Hopefully, they will develop a strain of rodent that exhibits such a reaction so as to serve as a model for mania. Of course, this would only go to reinforce the notion that there must be a genetic bipolar diathesis present to >display a manic reaction to antidepressants.
> It is my contention that long term rat studies may show things that the short term ones don't. Rat studies are brief, but in yours and my mothers case, a manic reaction was not evident right away.It took at least 6 months to emerge. This is in contrast to stimulant-induced hyperlocomotive or psychotic states.
> > My mania lasted for weeks after the >antidepressants were discontinued, despite >lithium treatment.
> Hey I've got a good one for you. An interesting phenomina, is that sometimes severe manic episodes can happen upon *discontinuation* of an antidepressant.Not news to me. Happened to me 3 times with Nardil. The abstracts on the web page you cited demonstrate this and refer to the patients as being bipolar. I also experience an improvement when tricyclics are withdrawn quickly.
> Now would these people be bipolar? I would argue no. They are undergoing a dopamine rebound. Regular people + dopamine overflow = strange behavior.
We might be getting just a little too theoretical here to attend to the clinical question being asked.
> >I think this is one factor
> >that leads me to believe that a manic reaction >to antidepressants is fundamentally different >from the acute behavioral states produced by >psychostimulants. Mania involves a self->perpetuating process, most likely effected by >kindling and probably facilitated through second >messenger events.
> Stimulants can cause seizures in no time at all. I guess that implies they can cause kindling in no time at all too?If the seizure threshold for subsequent exposures is reduced, it obviously can.
I think this question relates to matters of threshold (sensitivity) and inertia (length of episode). How much exposure (dosage; time) is necessary for the manic event to occur? I imagine the threshold is lower for someone who is bipolar. There might not even be a threshold (too high a threshold) for someone who is healthy. How long will the reaction persist after the provocative medication is discontinued? I should think that in someone who is bipolar, the longer the mania is allowed to continue, the greater is its inertia and tendency to persist after drug discontinuation. The interesting question is whether or not an inertia can be kindled in someone whom is not bipolar. I imagine the rodent studies can be used as a model for this.
> > Again, Depakote would have prevented this as my >mania are very responsive to it. It is also >responsive to Zyprexa, but not to the older APs. >I should think that combining Nardil and Zyprexa >would be a great combination for bipolar >depression.
> Depakote can be helpfull. It has a stronger anti-kindling effect than lithium. Lithium can actually be proconvulsant.
You are a wealth of knowledge and understanding. I only wish my inability to read and remember things were equal to yours.
> I think that the moment we understand how these drugs work, is the moment we can quantify (with any certainty) how and why they fail.
By saying "how these drugs work", are you admitting that they do indeed work?
:-)
- Scott
poster:SLS
thread:620137
URL: http://www.dr-bob.org/babble/20060315/msgs/621294.html