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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by anita on October 13, 2000, at 23:00:20
Hi Cam,
Some time ago you wrote a post about how risperidone may affect right-brain dysfunction, and zyprexa left-brain dysfunction. Do you know what this means exactly in terms of depression?
I'd like to try adding on a small dose of one of the new antipsychotics (to zoloft and lamictal), theoretically for the 5HT2A antagonism. From what I've read, it seems that while risperidone has a higher affinity for 5HT2A, zyprexa actually tends to be more helpful for depression. Also, I've read that seroquel is not a good add-on for depression. Can you tell me what you think about this? My unresolved depressive symptoms are primarily apathy, social phobia, and lack of willpower/motivation.
thanks a lot,
anita
Posted by Cam W. on October 13, 2000, at 23:39:26
In reply to Q. for CAM W. re risperdal vs. zyprexa, posted by anita on October 13, 2000, at 23:00:20
> Hi Cam,
>
> Some time ago you wrote a post about how risperidone may affect right-brain dysfunction, and zyprexa left-brain dysfunction. Do you know what this means exactly in terms of depression?
>
> I'd like to try adding on a small dose of one of the new antipsychotics (to zoloft and lamictal), theoretically for the 5HT2A antagonism. From what I've read, it seems that while risperidone has a higher affinity for 5HT2A, zyprexa actually tends to be more helpful for depression. Also, I've read that seroquel is not a good add-on for depression. Can you tell me what you think about this? My unresolved depressive symptoms are primarily apathy, social phobia, and lack of willpower/motivation.
>
> thanks a lot,
> anitaAnita - I'd almost forgot about left/right brain thing. I was at a schizophrenia conference a couple of years ago and Dr.Scott Purdon from Alberta Hospital - Edmonton showed some PET scans of Zyprexa and Risperdal in action (Risp lighting up the right side and Zyp lighting up the left side). I really don't know what Scott thinks of this today, but I see him in a couple of weeks and I'll ask him.
As for depression, the above presentation was done before we really new that the atypical antidepressants were mood stabilizers. Every depression is unique. I don't think you could really generalize (or maybe you can) where Zyprexa or Risperdal seems to enhance neurotransmission. I don't think that we have depression subtyped that well, yet. Maybe in the near future.
Lamictal is an anticonvulsant/mood stabilizer, not an antipsychotic. It seems to work very well for stabilizing bipolar depression.
I think that the 5HT-2A/D2 ratio of Zyprexa is greater than Risperdal, but as to in vivo binding affinities, I'm not sure. Anyways, I am starting to think that tweaking the receptor, rather than irreverisibly binding to it causes different second messenger responses. In other words, the atypical antipsychotics may not need to bind tightly to the receptor to result in a medicinal effect. So, looking at binding affinities of atypical antipsychotics may be misleading (then again, I can't prove this).
Personally I feel that Zyprexa is a better, overall mood stabilizer, but Risperdal may work better as an adjunct to SSRIs in OCD. For antidepressant augmentation, the gold standard is still lithium. It augments the action of many antidepressants. Seroquel seems to work best in a subgroup of people with bipolar disorder, but it seems to have a more calming effect, than an antidepressant effect.
As for diagnosing your depression; that I can't do. I can't tell an affective disorder from a personality disorder from a schizophreniform disorder. I just do the drugs. The docs have to tell me what the diagnosis is before I am of any help.
I hope this helps - Cam
Posted by SLS on October 14, 2000, at 9:21:08
In reply to Re: Q. for CAM W. re risperdal vs. zyprexa » anita, posted by Cam W. on October 13, 2000, at 23:39:26
Hi Cam.
Regarding my side effects with risperidone:What I experienced was sort of like a combination of weakness and stiffness. I can't say that I was slowed-down at all. I didn't experience any tremulousness except in the legs when I would climb stairs. I guess I overreacted, but it was upsetting to have to walk so deliberately just to make sure that I didn't trip over my own feet. I couldn't help but to think that this was EPS, especially since it was my impression that risperidone was the most likely of the atypicals to produce them.
Is there an association between how early in neuroleptic treatment EPS appears and the risk of tardive-dyskinesia?
It is hard to tell, but risperidone may have been helping a bit. Except for the weight-gain thing, I have a better gut feeling about the efficacy of Zyprexa for treating depression. Of course, gut feelings leave quite a large statistical margin of error and everyone is different. What is your impression regarding these two drugs for treating depression? Interestingly, Zyprexa has been known to occasionally cause mania in schizoaffective disorder.
I am having a hard time deciding whether I should try Zyprexa next or go back and try risperidone first.
Regarding Zyprexa and weight gain: You often cite 8 months or so as being the time period within which most of the weight gain occurs. After this, the rate of gain plateaus. My question is, if I were to starve myself during these first 8 months and manage to maintain my current weight, would I then be able to eat normally after this 8 month period without experiencing some sort of rebound weight gain?
Thank you, Cam.
> I think that the 5HT-2A/D2 ratio of Zyprexa is greater than Risperdal, but as to in vivo binding affinities, I'm not sure. Anyways, I am starting to think that tweaking the receptor, rather than irreverisibly binding to it causes different second messenger responses. In other words, the atypical antipsychotics may not need to bind tightly to the receptor to result in a medicinal effect. So, looking at binding affinities of atypical antipsychotics may be misleading (then again, I can't prove this).Are you saying that this receptor "tweaking" is how these drugs exert their therapeutic effects, or that the benefit of this type of dynamic is that it yields fewer side effects or a diminished risk of TD?
Regarding TD, it would be my guess that to allow each receptor to be stimulated regularly, although with decreased frequency, would still allow for the continuation of second messenger events, and thus prevent an increase in gene transcription to upregulate the membrane. The percentage of occupancy at any one moment might be similar to the older drugs, but it would be like a game of receptor keep-away. How frustrating and demoralizing this must be for the D2s. Just babbling.
That some modification of the second messenger system by "tweaking" the receptor might produce a therapeutic effect is an exciting idea.
- Scott
Posted by anita on October 15, 2000, at 23:27:39
In reply to Re: Q. for CAM W. re risperdal vs. zyprexa » anita, posted by Cam W. on October 13, 2000, at 23:39:26
Hi again Cam,
Thanks for the info. I'd appreciate it if you would pass on any new info your friend may have. May I ask if you are a professional reseacher or doctor? I only ask because you seem to be one of the most knowledgeable contributors here.
> Anita - I'd almost forgot about left/right brain thing. I was at a schizophrenia conference a couple of years ago and Dr.Scott Purdon from Alberta Hospital - Edmonton showed some PET scans of Zyprexa and Risperdal in action (Risp lighting up the right side and Zyp lighting up the left side).I know it's probably foolhardy to generalize about areas of the brain "lighting up," but does it tend to mean that there is more activity in that area than before? I ask because I've read that the "right" side tends to regulate fear more than the left, and I'm interested in diminishing fear responses.
I'm just trying to decide which med (risperidone, ketanserin, or serzone) to try adding to my current ones. I know it's a crapshoot, but I like theorizing about this stuff.
anita
Posted by Cam W. on October 16, 2000, at 19:38:50
In reply to Re: Q. for CAM W. re risperdal vs. zyprexa » Cam W., posted by SLS on October 14, 2000, at 9:21:08
> I guess I overreacted, but it was upsetting to have to walk so deliberately just to make sure that I didn't trip over my own feet. I couldn't help but to think that this was EPS, especially since it was my impression that risperidone was the most likely of the atypicals to produce them.
>
•I'd probably overreact, too, but you seldom see any EPS problems with Risperdal™ (risperidone) at doses under 3mg daily (except in some elderly people).
>
> Is there an association between how early in neuroleptic treatment EPS appears and the risk of tardive-dyskinesia?
>
•I don't think that either can be predicted. It happens when and if it happens. EPS and TD are very patient dependent, you can't guess who will get it, except that seniors are far more vulnerable (classic case of YMMV).
>
> It is hard to tell, but risperidone may have been helping a bit. Except for the weight-gain thing, I have a better gut feeling about the efficacy of Zyprexa for treating depression. Of course, gut feelings leave quite a large statistical margin of error and everyone is different. What is your impression regarding these two drugs for treating depression? Interestingly, Zyprexa has been known to occasionally cause mania in schizoaffective disorder.
>
•The literature says that Zyprexa works slightly better than Risperdal for mania, but I have seen mixed reviews for both in augmentation of depression. Both do work for many people. Something tells me that Risperdal is better for depressive symptoms. I think I read that somewhere, but I can't be sure of the source.
>
> I am having a hard time deciding whether I should try Zyprexa next or go back and try risperidone first.
>
•You and your doc's mutual decision. I'm staying out of that one, as it is outside my area of expertise.
>
> Regarding Zyprexa and weight gain: You often cite 8 months or so as being the time period within which most of the weight gain occurs. After this, the rate of gain plateaus. My question is, if I were to starve myself during these first 8 months and manage to maintain my current weight, would I then be able to eat normally after this 8 month period without experiencing some sort of rebound weight gain?
>
•I've heard people say that after 8 months (to a year) that they don't feel as hungry as they use to. But, I have seen about 75% of people gain some noticeable weight with Zyprexa (not everyone, though - Another of life's mysteries). I can't guarantee that after 8 months of eating properly that you won't gain weight, but once aquired, good eating habits become second nature (yeah, right; who am I kidding?).
>
> Are you saying that this receptor "tweaking" is how these drugs exert their therapeutic effects, or that the benefit of this type of dynamic is that it yields fewer side effects or a diminished risk of TD?
>
•Perhaps differential cFos induction in the prefrontal cortex and the basal ganglia? See below.
>
> Regarding TD, it would be my guess that to allow each receptor to be stimulated regularly, although with decreased frequency, would still allow for the continuation of second messenger events, and thus prevent an increase in gene transcription to upregulate the membrane. The percentage of occupancy at any one moment might be similar to the older drugs, but it would be like a game of receptor keep-away. How frustrating and demoralizing this must be for the D2s. Just babbling.
>
•Dr.Phil Seemans (the guy who developed the receptor site theory) gave a talk and basically said that maybe the reason that atypical antipsychotics (AAP) have such low D2 binding affinities, yet exert antipsychotic activity, may be that the AAP may be tweaking the receptor, therefore what you get when you do a binding affinity assay, you are actually only getting snapshot of D2 binding activity. I think that maybe the D2 receptors are somehow preferentially blocked in the prefrontal cortex, but not in the basal ganglia (perhaps due to a modification in the leak of dopamine in the area). These two brain areas seem to both use dopaminergic pathways, but are modulated differently.
>
> That some modification of the second messenger system by "tweaking" the receptor might produce a therapeutic effect is an exciting idea.
>
•I don't know if this is true and I can't prove it, but it sounds good (a sure sign that there is some faulty logic in the theory, somewhere).•Your partner in pondering - Cam
Posted by Cam W. on October 16, 2000, at 19:49:46
In reply to Re: Q. for CAM W. re risperdal vs. zyprexa » Cam W., posted by anita on October 15, 2000, at 23:27:39
Anita - I am just a community pharmacist that works with a mental health clinic and likes to read a lot. I like this board because we share info and correct each other when we goof. I've learned almost more here, than I have in 16 years as a pharmacist.
As to your atypicals for fear, I will ask Dr.Purdon when I see him in early November. This is one of those challenging questions that I like.
As to choosing a medication, I leave that up to the docs unless I am asked for an opinion, especially in cyberspace where I do not have access to files or histories. It would be unethical for me to try to pick a med for someone, especially when I don't know who they are or what their situation is.
Talk to you soon - Cam
This is the end of the thread.
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