Psycho-Babble Medication Thread 696107

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And Canada....

Posted by ed_uk on October 19, 2006, at 15:45:50

In reply to Long-acting quetiapine (Seroquel SR) filed for...., posted by ed_uk on October 19, 2006, at 15:40:04

AstraZeneca has also recently applied to the Canadian authorities for approval of Seroquel SR.

 

Patent extender.........

Posted by ed_uk on October 19, 2006, at 15:58:08

In reply to Long-acting quetiapine (Seroquel SR) filed for...., posted by ed_uk on October 19, 2006, at 15:40:04

.......definitely.

Useful clinical addition.....

Maybe for a few people. Is it that hard to remember to take it twice a day? I imagine many people deliberately 'forget' their morning dose in particular. I suppose AstraZeneca are going to make a big deal out of how it will 'improve the low compliance seen in the treatment of schizophrenia' or something. Funny really, given that 'compliance' with Seroquel seems to be *particularly* low despite the low incidence of EPS.

Ed

 

Re: Great news.... » ed_uk

Posted by Maximus on October 19, 2006, at 15:59:45

In reply to And Canada...., posted by ed_uk on October 19, 2006, at 15:45:50

> AstraZeneca has also recently applied to the Canadian authorities for approval of Seroquel SR.

They will apply it too for the treatment of Generalized Anxiety Disorder, GAD.

SR version will be very helpful. Bye.

 

seroquel...

Posted by med_empowered on October 19, 2006, at 16:01:25

In reply to Patent extender........., posted by ed_uk on October 19, 2006, at 15:58:08

yeah, I really don't get it. All of a sudden, seroquel has gone from being "that other atypical" to being great for...anxiety, bipolar, agitation, etc. etc. Its kind of amazing, since the drug really isn't that great.

Plus..I seem to recall reading that seroquel has a tendency to induce dopamine supersensitivity (more so than other atypicals, I guess). I forget the mechanism..something about loose binding mixed with a short half-life (kind of like Paxil withdrawal, I guess) but...its rough stuff.

 

Re: seroquel... » med_empowered

Posted by ed_uk on October 19, 2006, at 16:18:59

In reply to seroquel..., posted by med_empowered on October 19, 2006, at 16:01:25

Hi Med,

CATIE found that Seroquel had the highest drop-out rate among users, with 82 percent of patients discontinuing treatment within 18 months.

That compared to 64 percent for patients on Zyprexa, 74 percent for Risperdal, 79 percent for Geodon and 75 percent for the potent typical neuroleptic perphenazine.

>great for...anxiety, bipolar, agitation, etc. etc

From the AstraZeneca website........

'Seroquel SR will importantly extend the life cycle of Seroquel because the patent will be protected until 2017'

And of course......

'In addition to the Schizophrenia indication, I’m delighted to tell you we are planning a clinical program for Seroquel SR in Bipolar Disorder. This will enable submissions for Bipolar Depression and Mania globally in 2008 with this exciting, new formulation. Again, our aim is for the SR formulation to offer differentiating benefits compared to the IR formulation in Bipolar Disorder by providing a simple titration scheme that will enable a patient to reach a once-daily target dose earlier. The clinical trial program for SR will also include a broader patient population than the current bipolar data on IR with the inclusion of mixed and rapid cyclers'

Also.........

'A new clinical program is underway to study Seroquel SR in Major Depressive Disorder and Generalized Anxiety Disorder which will deliver indications from 2009'

It made me laugh how they say it will 'deliver indications'

And as we already have noticed......

'The depression market is currently worth 19 billion USD, while currently relatively flat our view is that this market will return to growth driven predominantly by increasing usage of atypicals'

>I seem to recall reading that seroquel has a tendency to induce dopamine supersensitivity (more so than other atypicals, I guess). I forget the mechanism..something about loose binding mixed with a short half-life

I've read something similar. I think it was saying that people tended to relapse particularly rapidly when Seroquel was discontinued and that tolerance sometimes developed to its antipsychotic efficacy.

Ed

 

Re: seroquel... » ed_uk

Posted by Phillipa on October 19, 2006, at 18:21:33

In reply to Re: seroquel... » med_empowered, posted by ed_uk on October 19, 2006, at 16:18:59

Ed how can it work for depression. It proves my theory that high anxiety leads to depression. It's a scam to get people off benzos. What about the diabetes lawsuit on zyprexa? Love PJ O

 

Re: seroquel...

Posted by willyee on October 19, 2006, at 23:08:38

In reply to Re: seroquel... » ed_uk, posted by Phillipa on October 19, 2006, at 18:21:33

> Ed how can it work for depression. It proves my theory that high anxiety leads to depression. It's a scam to get people off benzos. What about the diabetes lawsuit on zyprexa? Love PJ O

I was actual minutes away from being in the study,one was being done right down the block lol.

As for it being a scam,no way,it has effects on and i sure cant spell it now but serotonion.

I cant be technical like some,but unlike your common anti psych drugs,like the old school thorazine,seraquel is much more,there are a few receptor sites for serotonin,one or two are actualy noted to be responsable for ocd,and negative thoughts and behaviour.

Seraquel acts on these sites,as well as the positive sites that are feel good serotonion sites.


Buspar im not sure on but i believe is similiar,lowers serotoninin on the known negative sites.


If seraquel wasnt so sedating,even if its something u have to wait through,id have given it more of a fair shot.However i simply cant take the heavy sedation it carries.


Benzos arent going anywhere at all,they are used in ER when u come in with extreme anxiety,used through IV.


Regardless of the stigma,they work,and unless some breakthrough super drug comes around,benzos will not disapear,they unlike a lot of other drugs,have stood the test of time.


Go to a er in extreme paniac,unless u i suppose demand otherwise,chances are after your checked and its deemed safe,youll be pumped IV style full of more lilkly ativan.


As far as the diabetes,like lots of new drugs horrable negative effects are found after its been out,if it is indeed that dangerous,than hopefully it will then be properly removed.

 

Re: seroquel... » Phillipa

Posted by yxibow on October 20, 2006, at 3:13:46

In reply to Re: seroquel... » ed_uk, posted by Phillipa on October 19, 2006, at 18:21:33

> Ed how can it work for depression. It proves my theory that high anxiety leads to depression. It's a scam to get people off benzos. What about the diabetes lawsuit on zyprexa? Love PJ O


Its not a scam -- atypicals work on the high 5HT to D2 ratio.


Benzodiazepines don't really help depression, they actually can cause depression in those really prone to it, but more CNS depression than full depression. They're excellent and generally safe purely as directed for anxiety disorders.


Though I have mentioned it before that at least at this point in time I can't take Zyprexa because it causes (only in my experience) pseudoparkinsonism, nonetheless, my secondary depression broke in less than a week.


Besides Lithium, antipsychotics are the fastest methods to prevent suicide and antipsychotics are the fastest methods to halt certain forms of depression.


At a certain dosal range, Remeron mimics an atypical antipsychotic without the dopamine angle.


Atypicals form a blockade on serotonin receptors, a different form of antidepressant (as in Remeron, besides the alpha receptor which is activated, various 5HT receptors are blockaded in a certain quantity).


This doesn't mean that they are to be taken lightly (literally), as you mention the pitfalls of Zyprexa. A certain number of people will develop diabetes on Zyprexa if left too long without proper doctor evaluation. Continued tests (I continue to get tests frequently for Seroquel) are necessary and should be done and a diet/weight program should be instituted should there be issues and a possible change to a different AP.


As for lawsuits, well, this is a litigious society and while there are certain things that merit lawsuits, like Thalidomide and the like, it has been known for a while now about the lipid profile changes of some antipsychotics, unfortunately, some of them are those with the lowest risk of TD. I am not aware of the specifics of the lawsuit; this may have been filed before extensive Phase IV data had been collected.


There is a certain concept of informed consent, and I have been informed of possible things that could happen with Seroquel or any drug I take by my doctor (not that I haven't already probably researched it in PIs or the PDR being one of those patients who feels the need to self-educate and generally because I have a disorder that doesn't really fit into a known quantity per se.)

- tidings

Jay

 

neuroleptics+depression

Posted by med_empowered on October 20, 2006, at 12:04:17

In reply to Re: seroquel... » Phillipa, posted by yxibow on October 20, 2006, at 3:13:46

OK, here's the thing: with the atypicals, docs are saying "finally, we have drugs that are safe and effective for anxiety, depression, bipolar, schizophrenia, etc."...but, historically, antipsychotics have ALWAYS been used for these indications, and more.

When Thorazine and other phenothiazines hit the scene in the 50s, they were mostly looked on as "tranquilizers"; they weren't perceived as having magical anti-schizophrenic qualities until about 10years into the game. So...you see ads aimed at docs promoting Thorazine for anxiety, Thorazine for "senile agitation", Thora-Dex (that's right: Thorazine plus Dexedrine) for depression, Thorazine for "hyperkinetic children"..on and on it goes. And it was this way with the other drugs, too; Loxapine, for instance, was used in the 70s for various phobias and anxieties and depressive states. So was Moban. (I mentioned those because they were some of the later developed "typical" neuroleptics with a kinda sorta "atypical" profile).

Anyway...benzos can help depression, and so can low dose neuroleptics; the secret is that both of them can reduce anxiety, which drives up Depression Scale scores. Our concept of "depression" encompasses alot of what old-school docs thought of as "anxiety" or "psychic tension," so it makes sense that agents that specifically reduce anxiety (benzos) or induce apathy and reduced psychic intensity (neuroleptics) should reduce Depression scores, since alot of what's being measured is anxiety. ALso notice that antidepressants can reduce anxiety, and that some of them have neuroleptic-ish effects (apathy, indifference, dampening of dopamine, etc...there are even cases of AD induced EPS and TD, so the link may be stronger than we all though originally).

 

Re: neuroleptics+depression

Posted by linkadge on October 20, 2006, at 12:58:13

In reply to neuroleptics+depression, posted by med_empowered on October 20, 2006, at 12:04:17


I forget who, but some guy said that most antidepressants essentially work by reducing limbic dopamine.

SSRI's are more mood stabilizers, than they are antidepressants. They don't help you achieve your goals as much as they lower your standards.

Some depression is sensitive to this kind of activity, while other depression is not.

If you sit on the couch and watch TV all day, an antipsychotic isn't going to do much more than perhaps make you feel less guilty for sitting around.


Linkadge


 

New study:Diabetes risk same with Zyprexa and Sero

Posted by ed_uk on October 20, 2006, at 13:44:18

In reply to Re: seroquel... » Phillipa, posted by yxibow on October 20, 2006, at 3:13:46

20 October 2006

Am J Epidemiol 2006; 164:672-681

Diabetes risk associated with use of atypical antipsychotics

An observational study has examined the risk of developing diabetes in a cohort from a national sample of US Veterans Health Administration patients with schizophrenia (and no preexisting diabetes) who were using selected antipsychotic agents. The study involved 15,767 patients who started olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), or haloperidol (Haldol - the control group) in 1999–2001, after at least 3 months with no antipsychotic prescriptions. They were followed for just over 1 year. The study found that compared with the control group, diabetes risk was increased equally with new use of olanzapine (hazard ratio 1.64, 95% CI; 1.22, 2.19), risperidone (1.60, 1.19 to 2.14), or quetiapine (1.67, 1.01 to 2.76). In addition, diabetes risks were higher in patients aged under 50 years.

The study concluded “Assuming that the observed associations are causal, approximately one third of new cases of diabetes may be attributed to use of olanzapine, risperidone, and quetiapine in patients taking these medications. Prescribers should be mindful of diabetes risks when treating patients with schizophrenia.”


 

Re: neuroleptics+depression..(and apathy) » linkadge

Posted by Jay on October 20, 2006, at 15:42:44

In reply to Re: neuroleptics+depression, posted by linkadge on October 20, 2006, at 12:58:13

Well, I am *no* chemist, or claim to have ANY advanced knowledge about meds and such. Like many of us, I just like to investigate medications for their possible use....believing hope is eternal.(It is...)

All atypical antipsychotics will not just make "..you sit on the couch and watch TV all day." and "feel less guilty about it." Just adding my personal experience (5+ years of AP use), Zyprexa + AD's can make for good sleep and for a nice day with a "calm" attitude. How? I of course don't know exactly. But I think it has to do with both down AND up regulation, a bit like Abilify, but not to the same degree. Zyprexa is shown to increase concentrations of Dopamine in certain parts of the brain. Risperdal works a bit on the serotonin system which seems to help with sleep. Right now I take a combo of Zyprexa and Risperdal, (plus AD's and MS's), and I function quite well. What I mean by that is that I still get upset over things I should, and I still get a bit angry, or tired, or sad, when I should. But it doesn't mean my whole world is falling apart like it did before medications! Man, THE WAY SOME PEOPLE POST FRIGHTENING STORIES really proves to me that, many people possibly don't, or haven't tried enough or a large enough combination of meds. If you think you have, I will challenge anyone to compare lists with me. :-)The following articles focus more on then just depression, but on the concept of apathy as suggested by Link. Here are a couple of articles I just had a bit of time, to paste.

-----
http://snipurl.com/zyw7

Efficacy of atypical antipsychotics in depressive syndromes.

Lilly France, 13 rue Pages, 92158 Suresnes cedex, France. quintin_philippe@lilly.com Quintin P,
Thomas P.


Depression is a frequent symptom in psychiatry, either isolated (major depression) or entangled with other psychiatric symptoms (psychotic depression, depression of bipolar disorders). Many antidepressant drugs are available with different pharmacological profiles from different classes: tricyclic antidepressants, monoamine oxydase inhibitors, selective serotonin reuptake inhibitors (SSRI). However, there are some limitations with these drugs because there is a long delay before relief for symptoms, some patients with major depression are resistant to treatment, there is a risk to induce manic symptoms in patients with bipolar disorders and these drugs have no effect on the psychotic symptoms frequently associated to major depression. The leading hypothesis for the search of more efficient new antidepressants has been the amine deficit hypothesis: noradrenaline and/or serotonin deficit and more recently dopamine deficit. Moreover, a dopamine deficit has been also hypothesized as the central mechanism explaining the negative symptoms of schizophrenia. These symptoms are the consequence of a deficit of normal behaviours and include affective flattening, alogia, apathy, avolition and social withdrawal. There is thus a great overlap between symptoms of depression and negative symptoms of schizophrenia. Atypical antipsychotics, in contrast with conventional neuroleptics, have been shown to decrease negative symptoms, most probably through the release of dopamine in prefrontal cortex, thus improving psychomotor activity, motivation, pleasure, appetite, etc. The dopamine deficit in cortical prefrontal areas was thus an unifying hypothesis to explain both some symptoms of depression and negative symptoms of schizophrenia. Studies in animal confirm this view and show that the association of an atypical antipsychotic drug and an SSRI (olanzapine plus fluoxetine) increases synergistically the release of dopamine in prefrontal areas. Moreover, most of the atypical antipsychotics have a large action spectrum, beyond the only dopamine receptors: their effects on the serotonin receptors--particularly the 5-HT2A and 5-HT2C receptors--suggest that their association to SSRI could be a promising treatment for depression. Indeed, SSRI act mainly by increasing the serotonin level in the synapse, thus leading to a non specific activation of all pre- and post-synaptic serotonin receptors. Among them, 5-HT2A/2C receptors have been involved in some of the unwanted effects of SSRI: agitation, anxiety, insomnia, sexual disorders, etc. The inhibition of these receptors could be thus beneficial for patients treated with SSRI. Amisulpride is an unique atypical antipsychotic that selectively blocks dopamine receptors presynaptically in the frontal cortex, possibly enhancing dopaminergic transmission. The antidepressant effect of amisulpride was shown in dysthymia in many clinical studies versus placebo, tricyclic antidepressants, SSRI or others. However, a shorter delay for symptom relief was not demonstrated for amisulpride as compared to comparative antidepressants. Other atypical antipsychotics (clozapine, olanzapine), which act on a large variety of receptors, have shown antidepressant effects--mainly in association with SSRI--in different psychiatric diseases: treatment-resistant major depression, major depression with psychotic symptoms and depression of bipolar disorders, with no increase of manic symptoms in this latter case. Moreover, the delay for symptom relief was greatly shortened. More comparative double-blind studies are required to confirm and to precise the antidepressant effects of atypical antipsychotics. Nevertheless, these studies suggest that atypical anti-psychotics could be of great value in depressive conditions reputed for their resistance to treatment with usual antidepressants. Particularly, new strategies emerge that combine atypical antipsychotics and antidepressants for greater efficacy and more rapid relief of depression symptoms.

----------------
http://snipurl.com/zywb

1: J Neuropsychiatry Clin Neurosci. 2005 Winter;17(1):7-19.

Apathy: why care?
van Reekum R,
Stuss DT,
Ostrander L.
Department of Psychiatry and Kunin-Lunenfeld Applied Reserch Unit, Baycrest Centre for Geriatric Care, University of Toronto, 3560 Bathurst St., Toronto, Ontario, M6A 2E1, Canada. rvanreekum@baycrest.org

This review presents data showing that apathy is common across a number of disorders. Apathy is not only common, but is also associated with significant problems: reduced functional level, decreased response to treatment, poor illness outcome, caregiver distress, and chronicity. Preliminary evidence of treatment efficacy exists for dopaminergic drugs and for amphetamines. *Strong evidence of efficacy exists for acetylcholinesterase inhibitors in Alzheimer's disease, and for atypical antipsychotics in schizophrenia*. Frontal-subcortical system(s) dysfunction is implicated in the causation of apathy; apathy subtypes based on the various frontal-subcortical loops may thus exist. Further research involving diagnosis, pathophysiology, and treatment is suggested.

-----
Jay

 

Re: neuroleptics+depression..(and apathy)

Posted by linkadge on October 20, 2006, at 18:22:40

In reply to Re: neuroleptics+depression..(and apathy) » linkadge, posted by Jay on October 20, 2006, at 15:42:44

Well, perhaps my statement was a bit of an overgeneralization. I suppose some people do find them effective for depression. Some people find that they make their depression worse.

Zyprexa was ok for sleep for me, but it seemed like such a high price to pay the next day, just for a med that got you to sleep.

One other consideration I heard somebody call into question was the following: While it is true that blockade of serotonin 5-ht2a/2c receptors will result in dopamine release in certain areas of the brain, the neuroleptic itself is going to block the some of the actions of that released dopamine, through dopamine receptor antagonism. So what is the net effect on receptor activation? I don't think we know.

Linkadge

 

Re: seroquel...

Posted by Phillipa on October 20, 2006, at 19:09:50

In reply to seroquel..., posted by med_empowered on October 19, 2006, at 16:01:25

Why is schizophrenia being compared to depression? Anxiety leads to depression. Control anxiety and hence no depression at least that's the way it works for me. I guess I must be a wierdo. Love Phillipa

 

Re: seroquel... » Phillipa

Posted by yxibow on October 21, 2006, at 1:59:24

In reply to Re: seroquel..., posted by Phillipa on October 20, 2006, at 19:09:50

> Why is schizophrenia being compared to depression? Anxiety leads to depression. Control anxiety and hence no depression at least that's the way it works for me. I guess I must be a wierdo. Love Phillipa


Everybody comes into this life with a different package... you're not a wierdo and you know that, Jan. What I think you're implying is that you have secondary depression concommittant with primary anxiety. That is, the fact that you have an anxiety disorder and you have challenged various medications, depresses and worries you. That isn't so hard to believe. But I would argue that medication is not the only part of a treatment plan in that case. Therapy can play a crucial role too.


Schizophrenia isn't per se being compared to depression at least from my take; it is just that some forms of psychotic depression, manic depression, and even MDD may require augmentation with a neuroleptic, hopefully an atypical to reduce the chance of EPS in affective disorder patients. And yes, I know, Ed, that atypicals carry a greater risk of diabetes. That is why it is important to have a collaborative relationship between your psychiatrist/psychopharmacologist and your general practitioner. I get regular screenings more than once a year. I also spend hard hours when I can in the gym and I attempt but dont always succeed to control my intake, which is definately enhanced in my opinion with Seroquel. This doesn't mean it can't occur all of its own; in fact it is. I'm fighting intake, and lipid changes as well. Excercise does do it, but I'm talking about flat out 15% grade walking at a clip in the gym. This isn't a one size fits all solution for some people -- genetics partially will determine diabetes risk in the first place.


Its a tradeoff; unknown to 2%+ or so TD risk (done with several studies, including a British journal), with lipid changes in -some- of the atypicals, or 10%, 20%, 30% TD risk, or more with high potency old line drugs.


Everything is a tradeoff; drugs that are meant to save peoples lives like chemotherapy, or amiodarone for arrythmia (the thought of my father having to inject himself for two weeks with that medication was mind boggling to say the least) which carries big side effects, it is an informed consent to take, and a choice to weigh sometimes between life with some negative outcomes, or death, which is entirely in the choices we make. I digress, but it is a frequent topic.

-- tidings

Jay

 

Re: seroquel...

Posted by linkadge on October 21, 2006, at 8:18:40

In reply to Re: seroquel... » Phillipa, posted by yxibow on October 21, 2006, at 1:59:24

The only think that will unveil the true likelyhood that atypical neuroleptics cause TD is time.

Linkadge

 

Re: neuroleptics+depression..(and apathy) » linkadge

Posted by Jay on October 21, 2006, at 9:02:29

In reply to Re: neuroleptics+depression..(and apathy), posted by linkadge on October 20, 2006, at 18:22:40

> Well, perhaps my statement was a bit of an overgeneralization. I suppose some people do find them effective for depression. Some people find that they make their depression worse.
>
> Zyprexa was ok for sleep for me, but it seemed like such a high price to pay the next day, just for a med that got you to sleep.
>
>
>
> One other consideration I heard somebody call into question was the following: While it is true that blockade of serotonin 5-ht2a/2c receptors will result in dopamine release in certain areas of the brain, the neuroleptic itself is going to block the some of the actions of that released dopamine, through dopamine receptor antagonism. So what is the net effect on receptor activation? I don't think we know.
>
>
>
> Linkadge


Linkadge:

I found Zyprexa works great with some of the more "stimulating" AD's, such as Effexor, but better with Prozac + Nortriptyline for me. Now, after a month or so use of it, up to the 10 mg mark, (which I take at bedtime), it seems to really help with my morning "dread", which is a kind of apathy. No, I am not no manic, "Whooopeee" type in the morning now, but I can get through things without feeling like ending it all right then and there, which was a symptom that has gone back many years. Even when I was a teen, early mornings where like swallowing shreds of glass while lugging around a 1 ton metal ball, and being peppersprayed right in the eyes at the same time.Add in the feeling like someone jared a pair of scissors into my back and kidneys, and made me drink a bottle of 120 proof vodka, and I think we are close.

Anyhow...you understand..I'm sure. :-) Even with the science, the mechanisms are at best, very loose and messy theories, obviously. Like you pointed out about the serotonin blockade and feedback loop. But, there is still some kind of "muking around" going on up there that seems to have some benefit, sometimes. The only evidence I honestly need, for anyone, is that if it relieves your symptoms, then it's done it's job. These meds are not mean't as, and are far from, a "cure". So I can have 5 out of 7 good days a week, rather then one single day, that's fine with me. But I would still try to reach for seven. Not "manic" days...just hum-ho days, with good and bad and all, but not falling to pieces. That is what I think some people gotta learn. Meds should not be used to induce some "manic" state, as I have seen happen on here.(And no, I don't mean with you, Linkadge. :)

Just IMHO...
Jay

 

Re: neuroleptics+depression..(and apathy)

Posted by willyee on October 21, 2006, at 9:06:13

In reply to Re: neuroleptics+depression..(and apathy) » linkadge, posted by Jay on October 20, 2006, at 15:42:44

> Well, I am *no* chemist, or claim to have ANY advanced knowledge about meds and such. Like many of us, I just like to investigate medications for their possible use....believing hope is eternal.(It is...)
>
> All atypical antipsychotics will not just make "..you sit on the couch and watch TV all day." and "feel less guilty about it." Just adding my personal experience (5+ years of AP use), Zyprexa + AD's can make for good sleep and for a nice day with a "calm" attitude. How? I of course don't know exactly. But I think it has to do with both down AND up regulation, a bit like Abilify, but not to the same degree. Zyprexa is shown to increase concentrations of Dopamine in certain parts of the brain. Risperdal works a bit on the serotonin system which seems to help with sleep. Right now I take a combo of Zyprexa and Risperdal, (plus AD's and MS's), and I function quite well. What I mean by that is that I still get upset over things I should, and I still get a bit angry, or tired, or sad, when I should. But it doesn't mean my whole world is falling apart like it did before medications! Man, THE WAY SOME PEOPLE POST FRIGHTENING STORIES really proves to me that, many people possibly don't, or haven't tried enough or a large enough combination of meds. If you think you have, I will challenge anyone to compare lists with me. :-)The following articles focus more on then just depression, but on the concept of apathy as suggested by Link. Here are a couple of articles I just had a bit of time, to paste.
>
> -----
> http://snipurl.com/zyw7
>
> Efficacy of atypical antipsychotics in depressive syndromes.
>
> Lilly France, 13 rue Pages, 92158 Suresnes cedex, France. quintin_philippe@lilly.com Quintin P,
> Thomas P.
>
>
> Depression is a frequent symptom in psychiatry, either isolated (major depression) or entangled with other psychiatric symptoms (psychotic depression, depression of bipolar disorders). Many antidepressant drugs are available with different pharmacological profiles from different classes: tricyclic antidepressants, monoamine oxydase inhibitors, selective serotonin reuptake inhibitors (SSRI). However, there are some limitations with these drugs because there is a long delay before relief for symptoms, some patients with major depression are resistant to treatment, there is a risk to induce manic symptoms in patients with bipolar disorders and these drugs have no effect on the psychotic symptoms frequently associated to major depression. The leading hypothesis for the search of more efficient new antidepressants has been the amine deficit hypothesis: noradrenaline and/or serotonin deficit and more recently dopamine deficit. Moreover, a dopamine deficit has been also hypothesized as the central mechanism explaining the negative symptoms of schizophrenia. These symptoms are the consequence of a deficit of normal behaviours and include affective flattening, alogia, apathy, avolition and social withdrawal. There is thus a great overlap between symptoms of depression and negative symptoms of schizophrenia. Atypical antipsychotics, in contrast with conventional neuroleptics, have been shown to decrease negative symptoms, most probably through the release of dopamine in prefrontal cortex, thus improving psychomotor activity, motivation, pleasure, appetite, etc. The dopamine deficit in cortical prefrontal areas was thus an unifying hypothesis to explain both some symptoms of depression and negative symptoms of schizophrenia. Studies in animal confirm this view and show that the association of an atypical antipsychotic drug and an SSRI (olanzapine plus fluoxetine) increases synergistically the release of dopamine in prefrontal areas. Moreover, most of the atypical antipsychotics have a large action spectrum, beyond the only dopamine receptors: their effects on the serotonin receptors--particularly the 5-HT2A and 5-HT2C receptors--suggest that their association to SSRI could be a promising treatment for depression. Indeed, SSRI act mainly by increasing the serotonin level in the synapse, thus leading to a non specific activation of all pre- and post-synaptic serotonin receptors. Among them, 5-HT2A/2C receptors have been involved in some of the unwanted effects of SSRI: agitation, anxiety, insomnia, sexual disorders, etc. The inhibition of these receptors could be thus beneficial for patients treated with SSRI. Amisulpride is an unique atypical antipsychotic that selectively blocks dopamine receptors presynaptically in the frontal cortex, possibly enhancing dopaminergic transmission. The antidepressant effect of amisulpride was shown in dysthymia in many clinical studies versus placebo, tricyclic antidepressants, SSRI or others. However, a shorter delay for symptom relief was not demonstrated for amisulpride as compared to comparative antidepressants. Other atypical antipsychotics (clozapine, olanzapine), which act on a large variety of receptors, have shown antidepressant effects--mainly in association with SSRI--in different psychiatric diseases: treatment-resistant major depression, major depression with psychotic symptoms and depression of bipolar disorders, with no increase of manic symptoms in this latter case. Moreover, the delay for symptom relief was greatly shortened. More comparative double-blind studies are required to confirm and to precise the antidepressant effects of atypical antipsychotics. Nevertheless, these studies suggest that atypical anti-psychotics could be of great value in depressive conditions reputed for their resistance to treatment with usual antidepressants. Particularly, new strategies emerge that combine atypical antipsychotics and antidepressants for greater efficacy and more rapid relief of depression symptoms.
>
> ----------------
> http://snipurl.com/zywb
>
> 1: J Neuropsychiatry Clin Neurosci. 2005 Winter;17(1):7-19.
>
> Apathy: why care?
> van Reekum R,
> Stuss DT,
> Ostrander L.
> Department of Psychiatry and Kunin-Lunenfeld Applied Reserch Unit, Baycrest Centre for Geriatric Care, University of Toronto, 3560 Bathurst St., Toronto, Ontario, M6A 2E1, Canada. rvanreekum@baycrest.org
>
> This review presents data showing that apathy is common across a number of disorders. Apathy is not only common, but is also associated with significant problems: reduced functional level, decreased response to treatment, poor illness outcome, caregiver distress, and chronicity. Preliminary evidence of treatment efficacy exists for dopaminergic drugs and for amphetamines. *Strong evidence of efficacy exists for acetylcholinesterase inhibitors in Alzheimer's disease, and for atypical antipsychotics in schizophrenia*. Frontal-subcortical system(s) dysfunction is implicated in the causation of apathy; apathy subtypes based on the various frontal-subcortical loops may thus exist. Further research involving diagnosis, pathophysiology, and treatment is suggested.
>
> -----
> Jay
>
>
>
>

Wow link your perspective on drugs was so evident this time it brought this guy out to post an entire page,i agree with him too.I and Dr bob i really dont know how im supposed to word it,i know one way is the correct,so ill try,

I FEEL that counch comment was very mean and unfair.Hope i was to say feel,and not believe i dunno.

Anyway correcting yourself afterwards is always a plus,put the stabbing already poked.

Lol what a mean generalization to put fourth among people you know are struggling to get help.

 

Re: seroquel... » yxibow

Posted by Jay on October 21, 2006, at 9:20:28

In reply to Re: seroquel... » Phillipa, posted by yxibow on October 21, 2006, at 1:59:24

> > Why is schizophrenia being compared to depression? Anxiety leads to depression. Control anxiety and hence no depression at least that's the way it works for me. I guess I must be a wierdo. Love Phillipa
>
>
> Everybody comes into this life with a different package... you're not a wierdo and you know that, Jan. What I think you're implying is that you have secondary depression concommittant with primary anxiety. That is, the fact that you have an anxiety disorder and you have challenged various medications, depresses and worries you. That isn't so hard to believe. But I would argue that medication is not the only part of a treatment plan in that case. Therapy can play a crucial role too.
>
>
> Schizophrenia isn't per se being compared to depression at least from my take; it is just that some forms of psychotic depression, manic depression, and even MDD may require augmentation with a neuroleptic, hopefully an atypical to reduce the chance of EPS in affective disorder patients. And yes, I know, Ed, that atypicals carry a greater risk of diabetes. That is why it is important to have a collaborative relationship between your psychiatrist/psychopharmacologist and your general practitioner. I get regular screenings more than once a year. I also spend hard hours when I can in the gym and I attempt but dont always succeed to control my intake, which is definately enhanced in my opinion with Seroquel. This doesn't mean it can't occur all of its own; in fact it is. I'm fighting intake, and lipid changes as well. Excercise does do it, but I'm talking about flat out 15% grade walking at a clip in the gym. This isn't a one size fits all solution for some people -- genetics partially will determine diabetes risk in the first place.
>
>
> Its a tradeoff; unknown to 2%+ or so TD risk (done with several studies, including a British journal), with lipid changes in -some- of the atypicals, or 10%, 20%, 30% TD risk, or more with high potency old line drugs.
>
>
> Everything is a tradeoff; drugs that are meant to save peoples lives like chemotherapy, or amiodarone for arrythmia (the thought of my father having to inject himself for two weeks with that medication was mind boggling to say the least) which carries big side effects, it is an informed consent to take, and a choice to weigh sometimes between life with some negative outcomes, or death, which is entirely in the choices we make. I digress, but it is a frequent topic.
>
> -- tidings
>
> Jay


This is the other "Jay"..lol. I think Jay #1 has a great perspective on the atypicals.

I'd like to add in my 2 bits here as well. There is a groundswell of thought combined with scientific based evidence (I know some of this because I work in a behavioural lab with Autistic kids) that within a few years, we may be looking at all mental illness' across the same spectrum. You can easily play "connect the dots" with symptoms from all, and the thinking is that the separation may not be as "separate" as we thought. Each "disorder" may shadow, or merge into others. The overlap between negative symptoms of Schizophrenia and depression is a good place to look. The positive symptoms look an awful like Psychotic Depression. Major Anxiety and Social Phobia share characteristics with the hypomanic dysphoric state of BP2. Hence, the anxiety and phobia are now being treated with Bipolar meds.

So, we are talking about 50 shades of grey here. Personally, I find diagnosis of little value. It's the *symptoms" that must be treated for relief.

Anyhow..just IMHO...
Jay (the other one:)

 

Re: seroquel...

Posted by linkadge on October 21, 2006, at 11:56:33

In reply to Re: seroquel... » yxibow, posted by Jay on October 21, 2006, at 9:20:28

No no. Don't let me get in the way of what works for you.

I guess I'm just thinking about better tools for the future.

Linkadge

 

Re: neuroleptics+depression..(and apathy)

Posted by linkadge on October 21, 2006, at 12:06:19

In reply to Re: neuroleptics+depression..(and apathy), posted by willyee on October 21, 2006, at 9:06:13

Ok.

Essentially, I am saying that antipsychotics do more to reduce guilt and anxiety, than they do to reduce anhedonia.

I think the comment about the drugs not doing a whole lot for atypical depression type features is fair. When I am in an state of apathy, and all I want to do is sit on the couch all day, zyprexa doesn't do a whole lot for me. Thats all I am saying.

I am not saying that zyprexa makes you a couch potato, or that anyone who takes it is a couch potato. I am just saying that if apathy is your main symptom, I think that there are better drugs than the atypical antipsychotics. Thats what I am getting at.

If my comments don't apply to your situation, then I'd like to hear your comments.

If I offend a babbler then I am sorry, but I am not going to oppologise for offending a drug.

Linkadge

 

Re: neuroleptics+depression..(and apathy) » linkadge

Posted by emme on October 21, 2006, at 12:19:59

In reply to Re: neuroleptics+depression..(and apathy), posted by linkadge on October 21, 2006, at 12:06:19

Hi Link,

>I am just saying that if apathy is your main symptom, I think that there are better drugs than the atypical antipsychotics. Thats what I am getting at.

I wonder if Abilify might be the exception to that, maybe due to the partial dopamine agonism. My personal experience is that it helps my apathy.

emme

 

Re: neuroleptics+depression..(and apathy)

Posted by linkadge on October 21, 2006, at 13:28:06

In reply to Re: neuroleptics+depression..(and apathy) » linkadge, posted by emme on October 21, 2006, at 12:19:59

There are always exceptions, and I am sure there are quite a few people who have found these medications usefull.

Its unfortunate that researchers can't better tease apart the theraputic effect from the effects which may detract.

Atypicals might be like 5 steps forward, 4 steps back.

In addition, theres not too much inscentive for more selective agents, since drug companies rather like when they have a single drug being used for everything.

The one drug fix all. Everbody gets better, but nobody gets better.

Linkadge


 

Re: seroquel... » linkadge

Posted by yxibow on October 21, 2006, at 14:18:33

In reply to Re: seroquel..., posted by linkadge on October 21, 2006, at 8:18:40

> The only think that will unveil the true likelyhood that atypical neuroleptics cause TD is time.
>
> Linkadge

Clozaril, 1990. Unique agent. Almost no known reported TD cases. Unique from other atypicals in some ways. Definite EPS. Definite unpleasant side effects. "Gold standard" beyond Haldol. In the lab plus outpatient, around 19 years.


Risperdal was introduced in 1993 and so had to be in trials in 1990. 16 years. Some TD. Especially at high doses since its a chemical cousin of Haldol. Higher EPS.

Zyprexa, 1996. Add a few years in trials, 13 years. Smaller amounts of TD, especially in a BJP psychiatric study of considerable amounts of patients that amalgamated it to about 1/2% per year. There has been at least a couple of new studies that have amalgamated all atypical antipsychotics (except in the elderly) to around the 2% range. Some EPS.

Seroquel, 1997, Add a few years in trials, 12 years. Minimal reports of TD, definate reports of somnolence. Lower EPS.


Yes, sometimes medications take longer to form conclusions -- old Mellaril is still out there with large QTc intervals while a campaign was staged against Geodon until it was again challenged with a 4,000 person study. I don't like the side effects with Seroquel but I take it for a particular reason. If I didn't have that reason (non psychotic in this case), I wouldn't be doing so.

So atypicals basically have been around as long as SSRIs. You can take your conclusion from that as one wishes. Is a decade enough? Two? Three? If we back up two decades we're at the last benzodiazepine (except the patent extender Xanax XR). Three, around the last tricyclic.

tidings

-- Jay

 

Re: seroquel...

Posted by linkadge on October 21, 2006, at 15:47:44

In reply to Re: seroquel... » linkadge, posted by yxibow on October 21, 2006, at 14:18:33

TD may take a while to manifest. If in part mediated by free radicals, then one might expect the dammage to be a function of time.

We are learning things now about the SSRI's that we had no idea of when they were first released.

Consider how long SSRI's were in clincial trials/development before the true incidence of sexual dysfunction was unveliled.

Linkadge



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[dr. bob] Dr. Bob is Robert Hsiung, MD, bob@dr-bob.org

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