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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by mogger on April 30, 2005, at 1:53:55
Hello,
I am wondering why do anti-psychotics are supposed to have anti-depressant effects when they block certain neuro transmitters? I thought that drugs like prozaq and zoloft actually inhibit these neuro transmitters from being destroyed and they are supposed to be THE ANTIDEPRESSANTS? I mention seroquel in particular as I hear it has anti-depressant effects. I am currently on zyprexa. I just don't get it when I also hear people say that anti-psychotics augment anti-depressants. Can anyone help explain this to me? Many thanks,
mogger
Posted by BIGDaddyachmed69 on April 30, 2005, at 2:05:45
In reply to why do antipsychotics have anti-depressant effect?, posted by mogger on April 30, 2005, at 1:53:55
> Hello,
> I am wondering why do anti-psychotics are supposed to have anti-depressant effects when they block certain neuro transmitters? I thought that drugs like prozaq and zoloft actually inhibit these neuro transmitters from being destroyed and they are supposed to be THE ANTIDEPRESSANTS? I mention seroquel in particular as I hear it has anti-depressant effects. I am currently on zyprexa. I just don't get it when I also hear people say that anti-psychotics augment anti-depressants. Can anyone help explain this to me? Many thanks,
> moggerI'm going to try and do the best I can to help you out there, mogger...first off, make sure never to be on an antipsychotic as your sole antidepressant. BAD idea. They are sometimes used to augment the antidepressant effects of the SSRIs, particularly Prozac as they now have Symbyax, basically Zyprexa with Prozac. It has been approved by the FDA to treat bipolar depression, so for whatever reason Zyprexa seems to have some sort of antidepressant effects. I'm just as confused as you are as far as the pharmacology...why would blocking the reuptake of serotonin cause a decrease in depression, while blocking certain serotonergic receptors could do the same. It's interesting too how the atypical antipsychotics also seem to have anti-OCD properties to their credit. Some also claim that they have anti-anxiety properties as well, but I just tend to think it's because they're generally sedating. Just my two cents, dawg.
BIGDaddyachmed69
Posted by banga on April 30, 2005, at 8:14:10
In reply to Re: why do antipsychotics have anti-depressant effect?, posted by BIGDaddyachmed69 on April 30, 2005, at 2:05:45
Some thoughts on my end-
The atypical antipsychotics primarily block 5ht2a receptors--one of the subtypes of sertotonin. It is thought that in the case of this action, it helps anxiety and depression and OCD. Most tricyclic antidepressants also block 5ht2a, it is perhaps this action that makes some of them powerful OCD meds. Antidepressant activity in SSRIS may be more related to activating other serotonin sites more powerfully, and may overshadow the activation of 5ht2a sites (which theoretically then would strengthern, not lessen antianxiety effects).
For me, it is clear 5ht2a blockage helps anxiety immensely. Abilify and Geodon have helped me powerfully. (But GABA-related meds such as the benzos not only don't help, they cause me to pluncge into depression--whic makes me wonder if there is a subtype of anxiety that is more related to 5ht2a)
Also, if you think about it depression (and OCD) involves obsessive rumination--a thought disorder, just as schizophrenia spectrum disorders are thought disorders. At least from that perspective, it makes sense antipsychotics would help rumination.
I didn't say it clearly, but basically that is my thinking on this subject.
Posted by linkadge on April 30, 2005, at 8:48:09
In reply to Re: why do antipsychotics have anti-depressant effect?, posted by banga on April 30, 2005, at 8:14:10
Banga explained it fairly well.
The antidepressant effect of SSRI's is thought to be a result of the activation of the possynaptic 5-ht1a receptors.
SSRI's generally raise serotonin at all serotonin receptors including the ones that cause side effects.
For instance 5-ht3 agonism generally causes nausia, and GI disturbance, this can be one symptom of depression as well. AD's like remeron block this receptor and therefore cause less nausia.
So its not really about raising serotonin or lowering serotonin but rather getting it to the right place.
Linkadge
Posted by mogger on April 30, 2005, at 12:57:14
In reply to Re: why do antipsychotics have anti-depressant effect?, posted by linkadge on April 30, 2005, at 8:48:09
thanks everyone! most helpful!
Posted by Phillipa on April 30, 2005, at 19:33:32
In reply to Re: why do antipsychotics have anti-depressant effect?, posted by mogger on April 30, 2005, at 12:57:14
And very interesting. Fondly, Phillipa
Posted by chemist on May 1, 2005, at 3:10:42
In reply to Re: why do antipsychotics have anti-depressant effect?, posted by Phillipa on April 30, 2005, at 19:33:32
hello there, chemist here...one item missing from this discourse is the role of dopamine in positive/negative affect (in the context of schizophrenia and depression, at least) and the modulatory role of serotonin. positive affect in schizophrenia is overproduction and reuptake of dopamine in D_{2}/D_{3} couples in the mid-brain, and 5-HT_{2} agonism gone awry (some thought that way): antagonism of D_{2} (not to mention drug-dependent targeting of alpha_{1}, h_{1}, the aforementioned 5-ht_{2a,c}, some 5-ht_{1x}) will bring the attendant psychoses (5-HT_{2x} is a common target) and, in a milder state, mania to a lower tilt. some AAPs - ziprasidone, e.g. - can be classified as SSNRIs without a stretch. in last week's Nature, i read a precis from an article in Neuron concerning the duality, perhaps is the word, of dopaminergic neurons in DA AND 5-HT reuptake in rat brain, suggesting that perhaps the permissive serotonin hypotesis might be something to revisit. certainly anti-depressant effects attributed to relief of negative affect - again, DA implicated, but in another part of the brain - of schizophrenia are not at all out of the realm of implication of DA as well as 5-HT modulation. all the best, chemist
Posted by mogger on May 1, 2005, at 3:27:59
In reply to Re: why do antipsychotics have anti-depressant eff, posted by chemist on May 1, 2005, at 3:10:42
thanks chemist,
you sound brilliant. why do you think antipsychotics like seroquel have anti-depressant effects on Unipolar depressives (always low)?
mogger
Posted by ixus on May 1, 2005, at 3:38:28
In reply to why do antipsychotics have anti-depressant effect?, posted by mogger on April 30, 2005, at 1:53:55
> Hello,
> I am wondering why do anti-psychotics are supposed to have anti-depressant effects when they block certain neuro transmitters? I thought that drugs like prozaq and zoloft actually inhibit these neuro transmitters from being destroyed and they are supposed to be THE ANTIDEPRESSANTS? I mention seroquel in particular as I hear it has anti-depressant effects. I am currently on zyprexa. I just don't get it when I also hear people say that anti-psychotics augment anti-depressants. Can anyone help explain this to me? Many thanks,
> moggerHi Mogger,
there are "good and bad" serotonin receptors. Sometimes. While you are depressed, you lack serotonin, receptors become oversensitive. If you increase serotonin, your depression can get even worse expecially when "bad" receptors can not adapt (become less active) to higher dose of serotonin.
In conclussion, the goal is to increase the serotonin and/or upregulate "good" receptors and/or dowregulate "bad" once.
/ixus
Posted by ixus on May 1, 2005, at 4:02:47
In reply to Re: why do antipsychotics have anti-depressant eff, posted by mogger on May 1, 2005, at 3:27:59
> thanks chemist,
> you sound brilliant. why do you think antipsychotics like seroquel have anti-depressant effects on Unipolar depressives (always low)?
> moggerHi Mogger,
they can be of help because they antagonize 5-HT2A and 5-HT2C.
At higher dose you target more dopamine receptors which is not helpful in unipolar depression/anxiety.
There is also another hipothesis i.e. at lose dose you bind dopamine autoreceptors/presynaptic (they provide feedback for the releaser) thus increase dopamine release. At higher dose you targer also postsynaptic dopamine receptors - shut down dopamine transmission.
/ixus
Posted by mogger on May 1, 2005, at 23:30:52
In reply to Re: why do antipsychotics have anti-depressant eff » mogger, posted by ixus on May 1, 2005, at 4:02:47
chemist,
one more question and then I promise I will shut up. As you say that higher doses it stops dopamine transmission. Do you think that 300mg of Seroquel would do that or is it a low to mid enough dose to have some benefit (i.e. not stopping dopamine transmission) as opposed to not. Many thanks for your advise,
mogger
Posted by chemist on May 2, 2005, at 3:43:24
In reply to Re: why do antipsychotics have anti-depressant eff, posted by mogger on May 1, 2005, at 23:30:52
> chemist,
> one more question and then I promise I will shut up. As you say that higher doses it stops dopamine transmission. Do you think that 300mg of Seroquel would do that or is it a low to mid enough dose to have some benefit (i.e. not stopping dopamine transmission) as opposed to not. Many thanks for your advise,
> moggerhello there, chemist here...no bother, i apologize for not responding sooner...stopping transmission is a bit strong: putting the breaks on over-production and reuptake of DA by one or more specific receptors in a certain part of the brain to ease psychoses is perhaps more accurate...your question is likely best answered by experiment, as the dose you suggest might be (to *you*) more activating while to another it might still be sedating. i imagine that 25 to 50 mg per day is not going to ease psychotic breaks, nor would one ingest 1200 mg simply for a night's rest - the breakpoint from sedation may be absent or in, i suspect, the region you mention...sorry i can not be of more help, and do consider (with your doctor) a trial in the range you specify....all the best, chemist
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