Posted by SLS on May 1, 2000, at 12:43:37
In reply to Re: Shorter Trials with ADs, posted by AndrewB on May 1, 2000, at 8:44:50
> Scott,
>
> I can see that you didn't find much to agree with in my post. You didn't even agree with my name it seems!Sorry. Damned dementia.
> Concerning 2 week vs. 3 week or longer trials with tricyclics and MAOs, I'm open to what you have to say. Studies and their conclusions can be wrong.
These are.
Perhaps their observations are correct, but their conclusions are wrong. Dead wrong.
> But I tenatively agree with the idea itself behind 2 week trials; if after two weeks of taking an MAOI or a tricyclic a person should in good likelihood (70%-80%) have seen improvement, then it is time to move on to a new med. Let me know why you think the way you do.
What about the 20-30 percent? This is not acceptable. How can this 2 week protocol possibly be considered a logical way to treat a life-threatening illness, when 20-30 percent of cases will slip by? What is 7 more days to make sure that we catch them? No way does this make sense.
When treating outpatients, the clinician must rely upon the self-reporting of the patient. Such self-reporting is often very unreliable, and I doubt that most clinicians hand out HAMDs or facilitate daily observations by a professional. Even if they did hand out rating sheets, self-ratings are still unreliable. I am well aware that in a sizeable percentage of cases, a small improvement in mood can appear as early as one week into treatment. But this improvement is usually very small, and is often not recognized by the patient. This is especially true if there are associated psychological or emotional disturbances that mask any changes in biological function. In addition, there are often comorbid presentations with anxiety disorders, dysthymia, and other psychiatric conditions. How can it possibly be expected that 100 percent, or even the great majority of patients will be able to recognize the small improvement that MAY occur before their 14 day trial expires? No way does this make sense.
Oh yeah, remember that in quite a few cases, there is a tendency towards increased suicidal ideation early in treatment as they "improve". It appears BECAUSE their biology improves. I'm not sure a patient will report this suicidal ideation as an improvement.
> Concerning the D2/D3 agonists pramipexole and ropinirole, I'm not ready to say they are as efficious or as long lasting as amisulpride or sulpiride.
Neither am I. I really do hope to know, though.
> But neither am I as certain as you are that they aren’t.
I hope the questions I offered were not construed as certainty. My expression of certainty (believed certainty) is more similar to that which I have written above. I really did expect pramepexole to work in 1-3 days. However, I had no reason to believe that amisulpride wouldn't. That is why I asked you about your personal experience with it.
> I understand why you feel the way you do, knowing what you do about bromocriptine and the other older agonists. But perhaps these are different.
I was thinking the same thing, but I didn't want to substitute these older agonists for the ones you mentioned in my reply. It would have made for a forensic slight-of-hand.
> At least one small study has indicated that pramipexole is long lasting (6 months).
Was this pramepexole monotherapy? If not, what was it added to?
> As far how effective it is on its own I’ll wait to hear other people’s personal experiences with it.
That's why I am so interested to see someone create an inventory of what goes on here. You would make a good candidate to embark on this endeavour. From what I can surmise, you already have a hell of a head start.
"This mission, should you choose to accept it..."
This post will self-destruct in 5 seconds.
Oops, I guess not.
> Yes, D2 agonists act on the postsynaptic receptor and a drug like amisulpride acts on the presynaptic (at low doses). But I don’t see this as a big difference.
There are fundamental difference between them. They do very different things inside the synaptic-cleft. How "big" (important) is this difference, beyond the pharmacological activity, remains the judgement of the person contemplating it.
> In the end, amisulpride acts via stimulation of the postsynaptic receptor, just as pramipexole, the only difference being that the postsynaptic stimulation is done by the body’s dopamine instead of an agonist.
Different is different. The clinical end result cannot be deduced by the initial net effect at the synapse.
Prozac versus Pondamin. Provigil versus reboxetine. Amineptine versus Pemoline. Valium versus Depakote. Dexedrine versus Ritalin. Desipramine versus yohimbine. Celexa versus tianeptine? Paxil versus pindolol? Wellbutrin versus who the hell knows.
> Whether an agonist or the body’s dopamine is involved, the same issues of upregulation and downregulation and receptor sensitivities are involved and the effectiveness of amisulpride demonstrates that long term stimulation of the D2/D3 receptors does not need to lead to poop out.
Then what does? I have read posts from people inquiring what they should do next, as their amisulpride has pooped-out. I think you can find them archived over the last few months. Didn't you report diminishing returns, or was it simply that it did not address anhedonia? I don't remember exactly.
> But I have to admit, I’m sure there is a lot I don’t understand here.
Seeing as how this is such a common complaint among our most brilliant neuroscientists, you shouldn't be too hard on yourself.
:-)
> To answer your question, it has been my personal experience that both amisulpride and mirapex act in about 1 to 4 days.
But you were taking reboxetine at the time, weren't you?
> And yes, amineptine has been described as a direct acting DA medicine in relation to SSRIs and other ADs. It is all relative you know!
It is not relative. It either is or is not a ligand for those synaptic receptors being referred to. I have seen this same statement made before about other drugs. They are made out of ignorance.
> Finally, we both may agree that some of the D2/D3 receptors are located in parts of the brain central to some aspects mood (the limbic system).
I like the concept of primary versus secondary sites (or mechanisms) of dysfunction (or states of activity). I tend to lean in the direction of using at least one drug that targets the primary site to ensure continued response. Targeting the secondary site may provide a boost to compensate for any residual deficit (or excess) of activity there. Perhaps doing so can also help "kick-start" a response when a chronically hypostimulated or hyperstimulated area has become dysregulated. I thought it was an interesting concept, anyway.
> Causes of D2/D3 hypofunction that I have read of include lesions in the area and stress induced downregulation.
How would you compare the characteristics of D2 and D3 receptor sites and their associated pathways? Do you think the incorporation of D3 activity in a medication is particularly important in treating mood-disorders?
> Regardless of the ultimate cause of the downregulation, some D2/D3 active medicines have been shown to be efficious in upregulating D2/D3 receptor function on an ongoing basis.
Are these agonists of antagonists?
If the answer is not "both", then one must recognize the validity of discriminating between them. This would be a big difference.
I don't know the answer, so it wasn't a loaded question.
> Thank you for your stimulating and well informed disagreements.
Ditto.
Best wishes as always,
>
> AndrewB
Right back at ya',- Scott
poster:SLS
thread:31785
URL: http://www.dr-bob.org/babble/20000429/msgs/31839.html