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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by chess on December 13, 2006, at 10:28:38
Can someone please explain to me how atypical antipsychotics (Zyprexa, Seroquel, etc) work to stabilize mood if in fact they block dopamine and serotonin?
Posted by med_empowered on December 13, 2006, at 11:00:24
In reply to Atypical antipsychotics as mood stabilizers?, posted by chess on December 13, 2006, at 10:28:38
atypical antipsychotics are actually very much like the old antipsychotics--low-to-moderate doses of low-to-intermediate potency conventional (old school) antipsychotics (example would include Trilafon) are about as effective and cause about as many side effects and standard doses of these "atypical" agents.
In your brain, they dampen dopamine and serotonin, and some, like zyprexa, go all over the place and do things no one quite understands yet. These drugs, and the drugs that came before them, are tranquilizers. They reduce emotional arousal and vitality, reduce locomotor activity in lab animals (and humans--trust me) and overall serve as sedatives, albeit sedatives that sometimes prove useful in psychosis (although, judging by disconitnuation rates and suicide rates, they're really not *that great* for schizophrenia, either).
In the US, Thorazine hit the scene before Lithium did. Thorazine was a common treatment for mania and also sometimes for depression, anxiety, agitation, etc...it was known as a "chemical lobotomy," and for good reason.
"Mood stabilizers" redcue the frequency of mania/depression and lengthen the time spent not in a mood episode. So, if you usually have 2 depressions and 1 fit of mania a year, on a mood stabilizer you could be looking at 1 depression and no mania or (more likely) 2 depressions and no mania, since most "mood stabilizers" are more effective against mania than against depression--probably b/c any sedative can help with mania (barbiturates, opiates, antipsychotics, benzos, etc.)
Atypical antipsychotics are seen as better for depression in bipolar and the "negative symptoms" of schizophrenia than their predecessors. I find this to be more of an assumption than a fact. For along time, antipsychotic doses were very high, and high-potency agents were all the rage. These 2 factors would increase the rate of EPS (including subjective akathisia and neuroleptic-induced dysphoria), which could make negative symptoms worse (or cause them) and make depression worse (or cause it). The most striking thing about the new neuroleptics is their tendency to not cause obvious EPS, so I think you're able to get dopamine blockage w/o as many awful side effects..that doesn't make them wonder drugs; a lot of the problems with old drugs were a result of super-high dosages and poor patient selection.
Basically, the new antipsychotics can reduce frequency/intensity of mania (although they can also induce mania) and they can help with depression(although some people, including myself, find depression getting *worse* on "atypials). ALso, there's a risk of tardive dyskinesia--when these drugs first came out, the assumption was TD was a thing of the past, or it would now be very rare. Case reports have piled up for every available neuroleptic indicating TD; given that only a small percentage of any sort of adverse reactions will ever be reported+ the tendency of shrinks to blame TD on prior treatments or on "the illness" itself, my guess would be that the TD rates for the "atypicals" probably AREN'T that much better than for the older drugs, especially at higher doses, with other meds (such as lithium), and in high-risk groups (young people, older women).
That said...some people derive benefit. Personally, I'd try an anticonvulsant, lithium, benzos, or...anything before an atypical.
Posted by ronaldo on December 13, 2006, at 11:00:58
In reply to Atypical antipsychotics as mood stabilizers?, posted by chess on December 13, 2006, at 10:28:38
> Can someone please explain to me how atypical antipsychotics (Zyprexa, Seroquel, etc) work to stabilize mood if in fact they block dopamine and serotonin?
Good question chess. I'd also like to know. I've been on 5 mg Zyprexa for 4 years and now wish to come off it; but it is a very hard drug to come off. If I had been told how hard it is to come off I would never have taken it in the first place. Its darn expensive too. My treatment over the past 4 years has cost the equivalent of a brand new small motor car, something decent - middle of the range. The UK NHS has paid for this, no wonder they are short of money....
.....ronaldo
Posted by Maxime on December 13, 2006, at 12:35:23
In reply to Atypical antipsychotics as mood stabilizers?, posted by chess on December 13, 2006, at 10:28:38
> Can someone please explain to me how atypical antipsychotics (Zyprexa, Seroquel, etc) work to stabilize mood if in fact they block dopamine and serotonin?
I thought it was because they are dopamine antagonists.??
Maxime
Posted by chess on December 13, 2006, at 16:20:27
In reply to Re: Atypical antipsychotics as mood stabilizers?, posted by med_empowered on December 13, 2006, at 11:00:24
medempowered,
i can't remember what my doctor said exactly, but i think he said that due to the newer atypicals effecting serotonin (and that the older antipsychotics didn't) that this extra effect on serotonin causes some kind of negative feedback loop that controls any overactivity of dopamine blockage. Something like "Serotonin blockage keeps dopamine receptor fills to below 80%, and anything over that 80% is what causes pyrimidal symptoms. Also, the atypicals are more specific in where in the brain they work. The older antipsychotics were indiscriminate and binded to dopamine receptors all over the brain, while the atypicals are not as general and therefore not as problemsome.
atypical antipsychotics are actually very much like the old antipsychotics--low-to-moderate doses of low-to-intermediate potency conventional (old school) antipsychotics (example would include Trilafon) are about as effective and cause about as many side effects and standard doses of these "atypical" agents.
>
> In your brain, they dampen dopamine and serotonin, and some, like zyprexa, go all over the place and do things no one quite understands yet. These drugs, and the drugs that came before them, are tranquilizers. They reduce emotional arousal and vitality, reduce locomotor activity in lab animals (and humans--trust me) and overall serve as sedatives, albeit sedatives that sometimes prove useful in psychosis (although, judging by disconitnuation rates and suicide rates, they're really not *that great* for schizophrenia, either).
>
> In the US, Thorazine hit the scene before Lithium did. Thorazine was a common treatment for mania and also sometimes for depression, anxiety, agitation, etc...it was known as a "chemical lobotomy," and for good reason.
>
> "Mood stabilizers" redcue the frequency of mania/depression and lengthen the time spent not in a mood episode. So, if you usually have 2 depressions and 1 fit of mania a year, on a mood stabilizer you could be looking at 1 depression and no mania or (more likely) 2 depressions and no mania, since most "mood stabilizers" are more effective against mania than against depression--probably b/c any sedative can help with mania (barbiturates, opiates, antipsychotics, benzos, etc.)
>
> Atypical antipsychotics are seen as better for depression in bipolar and the "negative symptoms" of schizophrenia than their predecessors. I find this to be more of an assumption than a fact. For along time, antipsychotic doses were very high, and high-potency agents were all the rage. These 2 factors would increase the rate of EPS (including subjective akathisia and neuroleptic-induced dysphoria), which could make negative symptoms worse (or cause them) and make depression worse (or cause it). The most striking thing about the new neuroleptics is their tendency to not cause obvious EPS, so I think you're able to get dopamine blockage w/o as many awful side effects..that doesn't make them wonder drugs; a lot of the problems with old drugs were a result of super-high dosages and poor patient selection.
>
> Basically, the new antipsychotics can reduce frequency/intensity of mania (although they can also induce mania) and they can help with depression(although some people, including myself, find depression getting *worse* on "atypials). ALso, there's a risk of tardive dyskinesia--when these drugs first came out, the assumption was TD was a thing of the past, or it would now be very rare. Case reports have piled up for every available neuroleptic indicating TD; given that only a small percentage of any sort of adverse reactions will ever be reported+ the tendency of shrinks to blame TD on prior treatments or on "the illness" itself, my guess would be that the TD rates for the "atypicals" probably AREN'T that much better than for the older drugs, especially at higher doses, with other meds (such as lithium), and in high-risk groups (young people, older women).
>
>
> That said...some people derive benefit. Personally, I'd try an anticonvulsant, lithium, benzos, or...anything before an atypical.
Posted by blueberry1 on December 13, 2006, at 18:30:07
In reply to Atypical antipsychotics as mood stabilizers?, posted by chess on December 13, 2006, at 10:28:38
I don't know. I'm not sure they do. They block whatever is going wrong but don't stop it from happening.
Antipsychotics don't prevent whatever is going wrong, they just block the end result of it. Whatever is going wrong is still going wrong, it is just blocked from feeling it so much. Lithium and depakote make an effort to fix whatever is actually going wrong and prevent a cascade effect from happening, where the antipsychotics just block you from feeling those cascade events, though they are still happening.
That's how I see it anyway.
Antipsychotics might be good for acutely stopping, well, not stopping, but blocking a manic episode very quickly. But I think they are prescribed too often when other time tested milder treatments should be tried first.
Just opinion.
Posted by linkadge on December 13, 2006, at 19:53:38
In reply to Re: Atypical antipsychotics as mood stabilizers?, posted by blueberry1 on December 13, 2006, at 18:30:07
>Something like "Serotonin blockage keeps >dopamine receptor fills to below 80%, and >anything over that 80% is what causes pyrimidal >symptoms. Also, the atypicals are more specific >in where in the brain they work. The older >antipsychotics were indiscriminate and binded to >dopamine receptors all over the brain, while the >atypicals are not as general and therefore not >as problemsome.
The dopamine blockade will be dose dependant. The serotonin blockade will not reverse the dopamine blocade, but what it will do is act to release dopamine.
Certain serotonin receptors assert inhibitory controll over dopamine release. As a result blocking certain serotin receptors will release dopamine in certain areas of the brain.
In the end, doctors can say all they want how safe they are now, but only time will tell.Linkadge
Posted by stargazer on December 13, 2006, at 21:07:34
In reply to Re: Atypical antipsychotics as mood stabilizers?, posted by blueberry1 on December 13, 2006, at 18:30:07
Seroquel stopped a rapid decline of depression while on Cymbalta, which I believe made my depression worse with suicidal thoughts when none were present before beginning Cymbalta. I was amazed at how quickly the suicidality was reversed and how much quicker than other meds I have taken for similar situation.
Having said that, I have weaned off of it, knowing the downside to it. My pdoc trying to get me to reintroduce it to my current regime of Emsam 6 mg since I am not depressed but not at my baseline yet. I am resisting for now, but occasionally take 25 mg for insomnia although there's probably something much more specific I should take.
Anyway, I know what you mean by stopping the feeling and Seroquel did stop the suicidal thoughts which was a blessing. I would take it again if necessary since it was quick and helped me avoid a more drastic procedure.
Stargazer
Posted by Phillipa on December 13, 2006, at 21:54:01
In reply to Re: Atypical antipsychotics as mood stabilizers?, posted by stargazer on December 13, 2006, at 21:07:34
I too have taken seroquel for unipolar depression/anxiety. Mostly anxiety and found it made me feel strange and with the autoimmune problems and diabetes being autoimmune have decided no more. Was only a few time. Love Phillipa ps noticed quick tolerance unlike benzos
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