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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 PrettyLady on February 28, 2013, at 19:57:17
So I'm reading up on how antipsychotics work and it looks to me like they all block the four dopamine pathways (reduce dopaminergic neurotransmission). But atypical antipsychotic also block serotonin. I also understand that SSRI antidepressants increase serotonergic activity by stopping the reuptake of serotonin, and some have dopaminergic activity as well. It seems to me that this means that they have the opposite effect. One promotes activity, and one blocks it. So why are these sometimes prescribed together? I'm asking because I am taking Zoloft, and did better on Zoloft and Seroquel (atypical antipsychotic) at the same time. How can this be?
p.s. I'm also coming to understand that antagonism means to block, and agonism means to support. Is that correct?
Posted by Phillipa on February 28, 2013, at 21:32:08
In reply to Can antipsychotics+ antidepressants work together?, posted by PrettyLady on February 28, 2013, at 19:57:17
Sounds about right to me. Phillipa
Posted by tensor on March 1, 2013, at 1:28:14
In reply to Can antipsychotics+ antidepressants work together?, posted by PrettyLady on February 28, 2013, at 19:57:17
> So I'm reading up on how antipsychotics work and it looks to me like they all block the four dopamine pathways (reduce dopaminergic neurotransmission). But atypical antipsychotic also block serotonin. I also understand that SSRI antidepressants increase serotonergic activity by stopping the reuptake of serotonin, and some have dopaminergic activity as well. It seems to me that this means that they have the opposite effect. One promotes activity, and one blocks it. So why are these sometimes prescribed together? I'm asking because I am taking Zoloft, and did better on Zoloft and Seroquel (atypical antipsychotic) at the same time. How can this be?
You've got it wrong. The atypical antipsychotics do not block the "reuptake inhibition of serotonin", they block serotonin *receptors*. Take for instance the serotonin receptor 5HT2C, when serotonin stimulates this receptor it inhibits dopamine and noradrenaline in certain areas of the brain.
When the same receptor is blocked (can't be stimulated by serotonin) by an antidepressant or an atypical antipsychotic, the reverse is happening and can enhance the release of dopamine and noradrenaline, improving negative symptoms. That's the theory atleast./tensor
Posted by phidippus on March 2, 2013, at 14:39:23
In reply to Can antipsychotics+ antidepressants work together?, posted by PrettyLady on February 28, 2013, at 19:57:17
Certain atypical antipsychotics are prescribed alongside ADs because they agonize neurotransmitters implicated in anxiety and depression. For instance, Abilify agonizes 5ht1a receptors, as does Latuda. Seroquel has a strong affinity for norepenephrine, which is implicated in depression.
>I'm also coming to understand that antagonism means to block, and agonism means to support. Is that correct?
Yes
Eric
Posted by PrettyLady on March 2, 2013, at 16:22:37
In reply to Re: Can antipsychotics+ antidepressants work together? » PrettyLady, posted by phidippus on March 2, 2013, at 14:39:23
So, if the antipsychotic blocks, and the antidepressant supports, isn't that two opposite things going on there?
Posted by phidippus on March 2, 2013, at 18:15:19
In reply to Re: Can antipsychotics+ antidepressants work together? » phidippus, posted by PrettyLady on March 2, 2013, at 16:22:37
The antipsychotic does not block all the seratonin receptors the antidepressant agonizes. And in the case of some antipsychotics, certain seratonin receptors are agonized.
The main job of an antipsychotic is to antagonize dopamine receptors.
Eric
Posted by tensor on March 3, 2013, at 0:24:00
In reply to Re: Can antipsychotics+ antidepressants work together? » phidippus, posted by PrettyLady on March 2, 2013, at 16:22:37
> So, if the antipsychotic blocks, and the antidepressant supports, isn't that two opposite things going on there?
Atypical antipsychotics are used in depression with lower doses because they behave differently than at higher doses. At lower doses the blockage of 5HT2A is stronger than that of D2, which gives a higher dopamine output. At higher doses, the D2 blockage becomes dominant and dopamine is suppressed, giving an antipsychotic effect.
/tensor
Posted by bleauberry on March 3, 2013, at 12:25:53
In reply to Can antipsychotics+ antidepressants work together?, posted by PrettyLady on February 28, 2013, at 19:57:17
The agonism and antagonism stuff....it just aint that simple. For example, block a receptor and what might it do?....send signals to feedback loops to make more because something's blocked! So instead of blocking and getting less of something, it can actually result in more of something.
Studies with antipsychotics and antidepressants usually show synergistic changes of the levels of neurotransmitters in the brain. Prozac and zyprexa is a great combo for that, increasing all three neuros a by a lot (several hundred percent). Zyprexa and zoloft increased dopamine but not serotonin or NE. The different combos all behave differently.
The theory stuff is interesting and it's easy to get into it because we are depressed and nothing else is interesting except studying stuff about our own suffering. But theory doesn't help. Trying stuff does. You already discovered that yourself, before you even knew that AD+AP might be better than AD alone.
That said, I personally think seroquel is a poor choice. It is basically just one of the world's most powerful anti-histamines. Its other mechanisms are less in comparison. It displays a very high poopout rate, here at pbabble anyway. People that have been on APs for a long time and still getting benefit from them, that usually is either zyprexa or abilify, rarely seroquel.
Posted by PrettyLady on March 3, 2013, at 16:16:15
In reply to Re: Can antipsychotics+ antidepressants work together?, posted by bleauberry on March 3, 2013, at 12:25:53
That totally made me laugh, it's so true, when you're depressed as sh*t and obsessive behavior is raging, it's a recipe for long nights spent watching youtube videos about introductory pharmacology.
I think the zyprexa may be helpful as it seams to be starting to calm me down. I'm still not where I want to be, but it's early (only been two days). I'm noticing 2.5 is not sedating me much. In fact I can stay up after taking it. I don't know what that means, but I think it's interesting.
Thanks for all the great information. I'm sure I'll be asking more questions, it's good to know there are such knowledgable people hanging around these forums. :)
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