Psycho-Babble Medication Thread 842918

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Atypical Antipsychotic Augmentation Theories?

Posted by Bob on July 29, 2008, at 19:30:06

Can anyone shed any light on theories as to why adding an AAP to an AD might improve antidepressant response? On the surface it would seem like AP's crush dopamine and would therefore leave people feeling more depressed and flat. How can they possibly elevate mood, even if it is in concert with another antidepressant?

 

Re: Atypical Antipsychotic Augmentation Theories?

Posted by bleauberry on July 29, 2008, at 20:59:27

In reply to Atypical Antipsychotic Augmentation Theories?, posted by Bob on July 29, 2008, at 19:30:06

I love talking theories, even as I humbly submit to their uselessness.

Some possible things to ponder:

The AAPs do not permanently block dopamine receptors. They attach and let go frequently, allowing some dopamine to play its natural role. Very high doses are needed for all-out blockade.

The 5ht antagonism, DA antagonism, and NE antagonism all cause a release of more neurotransmitters.

Some pharmacologists theorize it is the 5ht antagonism doing the good work. It stimulates the release of all neuros, not just 5ht, and at the same time partially blocks the ones that cause mood problems.

Some of the DA receptors partially blocked are the ones sensing how much DA is present, so they will in turn send instructions to release more DA. Since the receving DA receptors are not totally blocked, some of that extra DA is getting through.

Some studies have shown that DA can be taken up into serotonin receptors, and that serotonin can be taken up into DA receptors...a possible explanation for AD sexual dysfunction. Some NE receptors also can take up DA. So as the neuros are all increased by AD+AAP, maybe some of those neuros are getting involved in crosstalk with other systems.

Anyway you look at it, many studies show that AAPs increase neuro levels in the brain, and the amount of the increases of each neuro are somehow influenced by the particular AD being used. For example, prozac+zyprexa increase all 3 neuros, above and beyond what prozac does alone. But zoloft+zyprexa increase only DA, above and beyond what zoloft does alone. Since prozac has some 5ht antagonism, that brings us back to that theory again.

Another possibility is that it all has nothing to do with neuros at all. Can't seem to find it now, but I saw an interesting study that showed how zyprexa turned up the volume on over a dozen different genes (weight gain being one), and turned down the volume on over a dozen other ones. Maybe one or several of those genes were tweeked in a way that affected mood.

Purely theories and probably totally wrong. The brain is too complicated.

 

Re: Atypical Antipsychotic Augmentation Theories? » bleauberry

Posted by Bob on July 29, 2008, at 21:38:20

In reply to Re: Atypical Antipsychotic Augmentation Theories?, posted by bleauberry on July 29, 2008, at 20:59:27

> I love talking theories, even as I humbly submit to their uselessness.
>
> Some possible things to ponder:
>
> The AAPs do not permanently block dopamine receptors. They attach and let go frequently, allowing some dopamine to play its natural role. Very high doses are needed for all-out blockade.
>
> The 5ht antagonism, DA antagonism, and NE antagonism all cause a release of more neurotransmitters.
>
> Some pharmacologists theorize it is the 5ht antagonism doing the good work. It stimulates the release of all neuros, not just 5ht, and at the same time partially blocks the ones that cause mood problems.
>
> Some of the DA receptors partially blocked are the ones sensing how much DA is present, so they will in turn send instructions to release more DA. Since the receving DA receptors are not totally blocked, some of that extra DA is getting through.
>
> Some studies have shown that DA can be taken up into serotonin receptors, and that serotonin can be taken up into DA receptors...a possible explanation for AD sexual dysfunction. Some NE receptors also can take up DA. So as the neuros are all increased by AD+AAP, maybe some of those neuros are getting involved in crosstalk with other systems.
>
> Anyway you look at it, many studies show that AAPs increase neuro levels in the brain, and the amount of the increases of each neuro are somehow influenced by the particular AD being used. For example, prozac+zyprexa increase all 3 neuros, above and beyond what prozac does alone. But zoloft+zyprexa increase only DA, above and beyond what zoloft does alone. Since prozac has some 5ht antagonism, that brings us back to that theory again.
>
> Another possibility is that it all has nothing to do with neuros at all. Can't seem to find it now, but I saw an interesting study that showed how zyprexa turned up the volume on over a dozen different genes (weight gain being one), and turned down the volume on over a dozen other ones. Maybe one or several of those genes were tweeked in a way that affected mood.
>
> Purely theories and probably totally wrong. The brain is too complicated.

Thanks! That was an excellent and informative post. Just what I was looking for.

 

Re: Atypical Antipsychotic Augmentation Theories? » Bob

Posted by Phillipa on July 30, 2008, at 12:01:01

In reply to Re: Atypical Antipsychotic Augmentation Theories? » bleauberry, posted by Bob on July 29, 2008, at 21:38:20

My feeling is just a feeling it relieves anxiety related to ad's hence feel better. Not a theory just thoughts. But I would rather use a benzo as not as many potential side effects but I'm not into combining a lot of meds. Phillipa

 

Re: Atypical Antipsychotic Augmentation Theories?

Posted by med_empowered on July 30, 2008, at 12:12:06

In reply to Re: Atypical Antipsychotic Augmentation Theories? » Bob, posted by Phillipa on July 30, 2008, at 12:01:01

I think Phillipa has a point. For a while, combo products like Triavil (perhpenazine+elavil) were all the rage; not only did the combos boost blood levels of one or both components, the neuroleptic soothed agitation and start-up probs and anxiety while the antidepresant helped perk up the patient. Old-school antipsychotics have been used in the treatment of all sorts of depression, either alone (like reserpine, for agitated depressives) or in weird combos (ThoraDex...for anxiety and depression).
I think the *big* change has been that now with the atypicals you're less likely to leave someone with a crippling mood disorder than with the older ones.

 

Re: Atypical Antipsychotic Augmentation Theories? » Phillipa

Posted by Bob on July 30, 2008, at 14:29:15

In reply to Re: Atypical Antipsychotic Augmentation Theories? » Bob, posted by Phillipa on July 30, 2008, at 12:01:01

> My feeling is just a feeling it relieves anxiety related to ad's hence feel better. Not a theory just thoughts. But I would rather use a benzo as not as many potential side effects but I'm not into combining a lot of meds. Phillipa


In my extremely limited experiences with very low and brief dosages of atypicals, it seems like they are more effective at relieving anxiety than benzos. This could be because I'm only referring to initial dosing effects. However, I don't like benzos too much. Seems like the smallest dosage changes for me precipitate depression and even suicidality. Getting off of them has been life threatening for me in the past.

 

Re: Atypical Antipsychotic Augmentation Theories? » med_empowered

Posted by Bob on July 30, 2008, at 14:30:49

In reply to Re: Atypical Antipsychotic Augmentation Theories?, posted by med_empowered on July 30, 2008, at 12:12:06


> I think the *big* change has been that now with the atypicals you're less likely to leave someone with a crippling mood disorder than with the older ones.


What type of crippling mood disorder were the older ones leaving people with?

 

Re: Atypical Antipsychotic Augmentation Theories?

Posted by linkadge on July 30, 2008, at 16:55:35

In reply to Re: Atypical Antipsychotic Augmentation Theories? » med_empowered, posted by Bob on July 30, 2008, at 14:30:49

Typical antipsychotics are used to produce certain models of depression.

It is theorized that certain antidepressants achieve their final target by enhanced responsiveness of d2/d3 receptors. Antipsychotics with potent d2/d3 blockade are appear to block the effect of many antidepressant compounds.

Antipsychotics with high 5-ht receptor occupancy in comparison to dopamine receptor occupancy may produce less depression owing to the ability of 5-ht receptor blockade to enhance dopaminergic neurotranssmission in certain brain regions.

Perphenazine is kind of an atypical in that it does have moderate inhibitory binding at 5-ht receptors.

I think that the more selective a drug is for postsynpatic dopamine receptors the more likely it is to produce depression, unless the depression is extremely agitated or psychotic or something.

Linkadge


 

Re: Atypical Antipsychotic Augmentation Theories? » linkadge

Posted by Bob on July 30, 2008, at 17:06:51

In reply to Re: Atypical Antipsychotic Augmentation Theories?, posted by linkadge on July 30, 2008, at 16:55:35


>
> I think that the more selective a drug is for postsynpatic dopamine receptors the more likely it is to produce depression, unless the depression is extremely agitated or psychotic or something.
>
> Linkadge
>
>
>
>
>
>
>

So following that theory, which atypicals would be most likely and/or least likely to cause depression?

 

Re: Atypical Antipsychotic Augmentation Theories?

Posted by linkadge on July 30, 2008, at 17:18:01

In reply to Re: Atypical Antipsychotic Augmentation Theories? » linkadge, posted by Bob on July 30, 2008, at 17:06:51

Its hard to say. I'd have to compare the dopamine to 5-ht receptor occupancy data and see if there is any data on the selectivity of these agents for pre/post synaptic dopamine receptors.

Linkadge

 

Re: Atypical Antipsychotic Augmentation Theories?

Posted by dcruik518 on August 4, 2008, at 7:57:09

In reply to Re: Atypical Antipsychotic Augmentation Theories?, posted by linkadge on July 30, 2008, at 17:18:01

I take a small amount of Abilify which stops me from pulling on my eyebrows and hairline; it works well for that.

Lindkage---do you know of any AD plus AAP combos that might work particularly well for social phobia and dysthymia? ~DRC


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