Posted by linkadge on March 17, 2006, at 16:16:11
In reply to Re: Never thought I'd hear this....., posted by SLS on March 17, 2006, at 12:00:02
>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.
It totally depends on your definition of mania. If mania is defined simply by symptoms and behaviors then yes, stimulants can cause mania. If you define mania as being the result of a specific geneticly induced biochemical state, then no perhaps stimulants do not produce mania. But because your reaction took place while you were taking drugs, there is no conclusive way to tell if it was your genes or not. As soon as you introduce that new variable, your personal biochemisty has been altered, and you can never be 100 percent certain that this is the way you would have reacted drug free.
>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?
One of the reasons I contend that the drugs are to blame is that doctors have alreadly known that certain antidepressants are more likely than others to cause these reactions. There are people who have had manic reactions to say "wellbutrin", but then never had a similar reaction to an SSRI. The reverse holds true too. Some site that the TCA's are more likely to cause psychotic reactions than the SSRI's.
You need to come visit me, and see me in person some day. Get to know me, and the people who know me. My friends and family, teachers, and doctors have noticed absolutely no manic behavior since stopping offending agents. I have not had a similar reaction before or since. Only time will tell, but keep in touch, I hope to proove you wrong!
>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.
That may be the safest course to take, but I think there are a lot of peope who will fall through the cracks. Antidepressant treatments vary widely on their abilities to enhance dopaminergic function. TCA's show the strongest ability to increase the sensitivity of limbic dopamine receptors. They increase the sensitivity of d3 receptors in the neucleus accumbens, even in normal controll rats. Anticholinergics can also cause mania, and psychotic reactions in healthy people. In addition TCA's dose dependantly lower the seizure threshold in normal mice. So theres 3 reasons.
1. Anticholinergic, deleriant like effects.
2. Lowered seizure threshold
3. Increased limbic sensitivity to dopamine
in pleasure centres.
>It took at least 6 months to emerge. This is in >contrast to stimulant-induced hyperlocomotive or >psychotic states.
TCA's effects on limbic dopamine receptors is acutally time dependant.
D2, and D3 expression often increases significantly after many months of treatment. This happened in normal mice. The receptors increased their expression well above baseline, these were not stressed or depressed rats. They were rats that were about to have robuslty enhanced dopaminergic response.
>The abstracts on the web page you cited >demonstrate this and refer to the patients as >being bipolar.
Doctors just lable anything that resembles bipolar as being bipolar. It makes their lives easier. But does it make our lives easier. People just don't fit into these categories. Lets turn this arugment around. If I can induce depression in somebody with drugs, does that mean they have unipolar disorder? Of course not. How about a combination of PCPA, cyproheptadine, atenolol, haldol, and dilanin, and reserpine, valium, naltrexone, and acutaine :) That would make any normal person jump off the nearest bridge. Does that mean that these drugs unleashed a underlying unipolar disorder?
>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.
No arguments there.
>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 think that in order for somebody to be considered "bipolar", their threshold needs to be low enough so that normal, life circumstances can trigger manic episodes.
>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.
Normal rats can be kindled. And that kindling can go on for a long time unless intervention has occured.
>You are a wealth of knowledge and understanding. >I only wish my inability to read and remember >things were equal to yours.
I don't aruge with fools :)
>By saying "how these drugs work", are you >admitting that they do indeed work?
You got me! I think they must do something for somebody. I guess what I am saying is that if we don't exactly know how they help, than how can we know for sure that they don't harm?