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How Seroquel Works


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http://thelastpsychiatrist.com/2010/02/how_seroquel_xr_works_part_1.html

 

the link above will tell you and if it stops working you can find it as a subtitle under this title below 

 

 

http://thelastpsychiatrist.com/clinical/antipsychotics/

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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moa%20pi%20seroquel.JPG

 

-result of Seroquel's effect on norepinephrine and the NET. 

 

What is the evidence for the proposition that Seroquel's antidepressant effect is mediated by norepinephrine?


Quetiapine is partially metabolized to norquetiapine.  Any pharmacologic (i.e. receptor) description of the Seroquel's effect must therefore include norquetiapine.

seroquel%20affinities.JPG

Quetiapine does not bind to the NET; but norquetiapine, its chief metabolite, is a potent inhibitor if it.  Tricyclics, Effexor, and Cymbalta all have considerable NET inhibition as well.  It's logical to conclude that when you eat a Seroquel, and it gets metabolized to norquetiapine, that it would then exert some action on the NET.

 

 At a clinically relevant dose of Seroquel, how much norquetiapine is there?

Not much.

It appears that, in contrast to the longstanding paradigm of post-Kohut modern psychiatry, there is more to the human body than serotonin and norepinephrine receptors.  I'm as terrified as you are.  I don't know what to believe anymore.

A study measured the NET occupancy to Seroquel and norquetiapine (administered independently) in monkeys after a single dose.  Norquetiapine produced 80% occupancy of the NET at low concentrations. 

However, in the nine suckers induced to participate in this other study, 300mg Seroquel XR  for 7 days generated 300nM concentrations of norquetiapine (as predicted above) and 35% NET occupancy in the thalamus.  150mg Seroquel XR-- the dose at which it functions as an antidepressant-- resulted in 19% occupancy.  That's not very much.

Consider that if Seroquel is metabolized to norquetiapine in monkeys as well, then a clinically relevant dose of Seroquel should produce clinically meaningful occupancy of NET (by the effect of its metabolite.)  It didn't.

The actual occupancy of the NET after 300mg Seroquel XR is quite low, 150mg even lower.

 

Understanding that the comparisons are not entirely fair, a blood assay in depressed humans found that after 8 weeks of Effexor 150mg, NET inhibition was 50%.  At 375mg, it was 60%.  Paxil, an "SSRI", blocked about 30% at 75mg.  Note that Effexor is only 55% protein bound (Seroquel is 80%) and thus in a real patient, there is more free Effexor to exert activity on the NET, which may be why it has such a larger effect on the NET despite a theoretically weak Ki (2200nM).

Despite this, the NET occupancy of a clinically efficacious dose of Seroquel XR (150mg) is likely too low to be the main cause of its antidepressant efficacy. 

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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the last psychiatrists comment to a question on this part

"No, not at all a bad thing. The argument here isn't that Seroquel doesn't work-- it does work, as evidenced by the clinical data (see part 2) and lots of people on it. However, the _explanation_ for the efficacy is wrong; worse, the wrong explanation is ok'd by the govt; worse, it causes something else to happen..."  

 

on to part 2

 

http://thelastpsychiatrist.com/2010/02/how_seroquel_xr_works_part_2.html

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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How can that fact that a lot of people are on it be used to mean it works? Then alcohol and pot work, too.

2009: Cancer hospital said I had adjustment disorder because I thought they were doing it wrong. Their headshrinker prescribed Effexor, and my life set on a new course. I didn't know what was ahead, like a passenger on Disneyland's Matterhorn, smiling and waving as it climbs...clink, clink, clink.

2010: Post surgical accidental Effexor discontinuation by nurses, masked by intravenous Dilaudid. (The car is balanced at the top of the track.) I get home, pop a Vicodin, and ...

Whooosh...down, down, down, down, down...goes the trajectory of my life, up goes my mood and tendency to think everything is a good idea.
2012: After the bipolar jig was up, now a walking bag of unrelated symptoms, I went crazy on Daytrana (the Ritalin skin patch by Noven), because ADHD was a perfect fit for a bag of unrelated symptoms. I was prescribed Effexor for the nervousness of it, and things got neurological. An EEG showed enough activity to warrant an epilepsy diagnosis rather than non-epileptic ("psychogenic") seizures.

:o 2013-2014: Quit everything and got worse. I probably went through DAWS: dopamine agonist withdrawal syndrome. I drank to not feel, but I felt a lot: dread, fear, regret, grief: an utter sense of total loss of everything worth breathing about, for almost two years.

I was not suicidal but I wanted to be dead, at least dead to the experience of my own brain and body.

2015: I  began to recover after adding virgin coconut oil and organic grass-fed fed butter to a cup of instant coffee in the morning.

I did it hoping for mental acuity and better memory. After ten days of that, I was much better, mood-wise. Approximately neutral.

And, I experienced drowsiness. I could sleep. Not exactly happy, I did 30 days on Wellbutrin, because it had done me no harm in the past. 

I don't have the DAWS mood or state of mind. It never feel like doing anything if it means standing up.

In fact, I don't especially like moving. I'm a brain with a beanbag body.   :unsure:

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LOL well ...good question actually you should read part 3 when I was trying to sort it and post it .. I got kicked out of SA just got back to it now... I was thinking that too when i read it and thinking of Ang... she drinks some wine.  The shrink who writes this is partial to rum. :) sometimes it sounds like a lot of rum... but whatever we all have something.  I can't drink I get sick. it is just not worth three days of sick to have one drink. 

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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Share on other sites

How Seroquel XR Works, Part 2

warren%20commission.jpg
The ongoing story of a government cover-up

Part 1 was here.  

 

Let's assume it did bind to the NET, how much of the efficacy should we attribute to norepinephrine?

 

In the pre/frontal cortex there are no pure dopamine transporters (DAT), and the NET is primarily responsible for dopamine's reuptake.  So the NET, which norquetiapine fully occupies/barely touches, transports about 50/50 norepinephrine and dopamine. 

 

So even if the NET is inhibited, the ultimate effect in the frontal lobe may be related to dopamine.

 

Are there any other better explanations for Seroquel's antidepressant efficacy?

 

It's odd that while the FDA has chosen to be unsure about the mechanism of action in psychosis, it is confident in the MOA in depression.  Here are some equally/more likely explanations for the antidepressant effect:

 

H1 antagonism: sure, why not?  6 points on a Hamilton for sleep, another 2 for weight gain...

 

Partial agonism at 5HT1a:  Think Buspar.

 

a2 antagonism:  (inhibitory autoreceptors.)  Blocking these would increase serotonin and norepinephrine release, etc.

 

Unfortunately,  a2 antagonism is a property only of quetiapine, not norquetiapine.

 

Why is that unfortunate?

 

Because if norquetiapine is marketed as a new drug...

 

 

But if norquetiapine does actually inhibit the NET, wouldn't that at least be a plausible mechanism for its efficacy?  Since Effexor and Cymbalta work...

 

I'll grant that it is evident Effexor and Cymbalta work; but who are you asking to tell you why they work?  Wyeth and Lilly?  That's like asking your future wife's ex-boyfriends to write her a letter of recommendation.  "She's so awesome, she'll make you really happy." Oh, I guess I should go shave my back then.

 

That's a very disturbing visual, Backbeard.

 

Let's do an abbreviated analysis for Effexor.  According to this non-porn site, the Ki for the SERT is 80nM and NET 3000nM (1000-6000).  This means it "prefers" to go to the serotonin transporter (SERT).

 

Consistent with this is PET data showing high SERT binding in striatum:

 

effexor%20sert.JPG

 

 

This is a comforting graph, and shows the "fountain" approach to understanding a "dirty" drug's effects. But note that the line isn't flat, it still trends upwards.  If the affinity for the SERT is 200-600 times that for NET,  then clinically meaningful effects on NET would have resulted in serotonin overload.

 

But that's speculation.  You've already shown that the Ki's are unreliable guides of in-vivo affinities and effects.

 

Ok:

 

What you want is a direct test of the operation of the NET in the human body.

 

If you inject tyramine into your friend, it will be taken up into the presynaptic NE terminal by the NET, where it will cause the release of norepinphrine.  The blood pressure then reliably goes up.

 

If you block the NET, this effect will also be blocked, since tyramine can't get in.  Nortriptyline, a tricyclic and "norepinephrine reuptake inhibitor" blocks the tyramine effect almost completely.(1)

 

What about Effexor?  If Effexor is an NRI, it should also block the blood pressure elevation.  Zoloft, not an NRI, should not block it-- the BP should go up.

 

 

tyr30.JPG 

This is ratio of post/pre blood pressures; >1 means tyramine caused BP to go up, <1 means tyramine couldn't get BP to go up.

 

What you see is that 75mg of Effexor was no more an NRI than Zoloft; and maprotiline (the NRI) turned Effexor 375mg into a cuckold. 

 

But surely Cymbalta has impressive clinically relevant NRI effects?

 

What dose of tyramine is needed to make the BP go up 30mmHg?  That's called the PD30.  If a drug blocks the effect (like desipramine, an NRI, would) than it would take more a higher dose of tyramine:

 

 

  TYR PD30 (mg)   Day 7 Day 8 Placebo (n=12) 7 [4-14] 6 [5-9] Duloxetine 80 mg (n=5) 9 [5-8] 7 [4-7] Duloxetine 120 mg (n=6) 6 [5-9] 4 [4-7] Desipramine 100 mg (n=11) 30 [22-82] 18 [12-31]

Well that's unfortunate. (2)

 

 

But then how can they claim Cymbalta is an NET? 

 

1.  By ki, the SERT/NET ratio is about 10, versus Effexor's 200, so in that sense you get the norepinephrine "earlier" in the dosing cycle; 

 

2. If it blocks the NET, then it should also decrease the cycle of norepinephrine turnover (since it isn't being taken back up and degraded.)  So there should be less NE and its metabolites in the urine.  And that's certainly what this study finds (abstract:)

 

Urinary and cardiovascular measurements suggest that duloxetine has an effect on NE synthesis and turnover, indicative of NE reuptake inhibition. 

"Suggest?"

 

 

NE%20metabolites%20cymbalta.jpgCompare the NRI desipramine (DMI) to placebo, note the decrease in urine NE and metabolites.  You can see that while the levels of NE and its metabolites decreased in the urine, Cymbalta resulted in a decrease in only the metabolites, but not NE itself.  Do you know why?  No one else does either.  

 

On the basis of this study we can reasonably conclude only that duloxetine is spelled with an x.

 

 

So you're saying that they arbitrarily decided on the mechanism of action of Seroquel by its barely detectable similarity to Effexor and Cymbalta, which themselves don't generate their efficacy the way they say they do and Seroquel hoped they did?

 

At this point, someone in the room should probably say "oops."

 

 

-----

 

Part 3.  (You mean there's a Part 3?)

----

 

1. One interesting conclusion of this is that it would therefore be safe to mix an MAOI with Pamelor.  THAT IS NOT A CLINICAL RECOMMENDATION.

 

2. If you want to make a gazillion dollars, perform the TYR30 test with Seroquel and norquetiapine.  Residents: I just gave you a treasure map.

 

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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part 3
 
MARCH 14, 2010
Swallow This: How Seroquel XR Works, Part 3
if you could only see the truth

 


Part 1 
Part 2



Now let's stop asking how, and ask what: what does this drug actually do?

FDA:


Major Depressive Disorder sNDA Submission

The FDA approval of SEROQUEL XR for MDD was based on a supplemental new drug application (sNDA) comprising findings from two Phase III, placebo-controlled studies that assessed the efficacy and safety of once-daily treatment with SEROQUEL XR as adjunctive treatment in patients with MDD.


Note the word adjunctive.  Two trials showed its efficacy as an adjunct.   Like Abilify, Seroquel is only indicated for use as a supplement to a failed/failing antidepressant.  Maybe it's a necessary combination of a serotonergic effect plus (a non-existent) noradrenergic effect, or some other synergistic mechanism; but it's an add-on, so get adding.


An adjunct-- to what?


study%202%20seroquel%20mdd.JPG
There's your data, it's one of the two trials the FDA used to grant the indication.  The other trial's data was nearly identical.  (1)

Seroquel was tested as an add-on to SSRIs, and also Effexor and Cymbalta.  (The top line is placebo + SSRI/SNRI.)  If we believe that at the doses used Effexor and Cymbalta are blocking the NET, and Seroquel at 150mg is doing the same, then why would we expect the addition of Seroquel to be of any use?  They're both fighting for the same site, only one can bind, so?  You wouldn't mix Paxil and Zoloft, would you?

So either the NET isn't relevant here; or, if it is, then those patients on Effexor/Cymbalta + Seroquel will not show greater improvement (e.g. as compared to Celexa + Seroquel).  And the pooled data you see above will appear less impressive because the Effexor and Cymbalta patients dragged the overall average down.

Or, more simply: if they did the study only with SSRIs, maybe the augmentation results would have been even better!

So either the FDA is wrong you shouldn't mix it with Effexor/Cymbalta, or you should because the FDA is wrong about the mechanism.  Good luck, have a drink.  Your next patient is the dumpster guy from Mulholland Drive.


You're frightening me with your talk of dumpsters and intimations of rum.

Drink up.

This is from the promotional slide deck that Astra Zeneca uses to detail doctors, showing the results of the two trials.


seroquel%20xr%206%20and%207.JPG


Take a good look at this slide, and compare it to the one above, from which it came.  Do you see anything weird?  Take minute.  

Stop looking at the data curves.  Stop looking at the p values.  What do you expect to see there?  You already know it's going to beat placebo or else they wouldn't have made a slide.  Do you really think you're going to discover something there?

This slide is an illusion like the impossible fork, you want to see this as a representation of something else instead of seeing it for what it is.

I'll give you a hint:

seroquel%20xr%206%20and%207%20redacted.J

What happened to studies 1-5?

Undoubtedly, your first thought will be that AZ hid the data.  I wish that was true.

This is a promotional slide.  The purpose of it is to push Seroquel.  That means that nothing on it is not either compelled by the FDA or on purpose to get you to believe.  They are accurately labeled studies 6 and 7 so that  there so doctors ask about the other 5 studies.  Why do they need doctors to ask?  Because the FDA forbids them from mentioning them.   So strict is this ban that the AZ reps are not even told by the company there are 5 other studies, so that they don't accidentally mention them.  I am not exaggerating.  The reps don't know.

You know what makes me happiest?  When the government considers certain information so disruptive that it not only doesn't it tell the citizens, it doesn't even tell other members of the government.  So that the only people who know are the heads of the government, and the heads of a for-profit corporation.

There's a word for that kind of thing.  But anyway.

So what were studies 1-5?

Studies 1-5 were all monotherapy studies-- specifically, 4 acute trials and one 6 month maintenance study.  And all but one acute study worked.(2)

More importantly, two of the trials that worked used 50mg.

In fact, AZ also submitted 5 other studies-- all positive-- to the FDA showing efficacy in GAD at doses starting at 50mg.


So this drug is efficacious as monotherapy in depression and anxiety?

Apparently so, and apparently at doses less than 150.  Of course, since the adjunct trials were only done using 150 and 300, those are the doses that get approved.  Safety, to the FDA, means they'd rather you get 3x to 6x the necessary dose-- along with a probably irrelevant drug-- than reveal that it worked as monotherapy.  


Wait a second-- if there's very little NET inhibition at 150mg, doesn't that probably mean there isn't any at all at 50mg?

Oops.


Why would Astra Zeneca want to convince us that the mechanism of antidepressant effect was NET inhibition, when there is so much evidence (that presumably they are aware of) that it isn't?

Astra Zeneca doesn't want to convince us of that: the FDA does.


----

Coming soon: Part 4



1. Note that 300mg was not better than 150mg.  And why would it be?  The higher the dose, the more dopamine blockade your getting, which isn't relevant to depression otherwise we'd be augmenting with Haldol, which we aren't.  (NB: which is why Abilify augmentation stays below 15mg.)

2. Seroquel 150 vs. Celexa 20 vs. placebo: no difference.


---
http://twitter.com/thelastpsych 

http://thelastpsychiatrist.com/2010/03/swallow_this_how_seroquel_xr_w.html

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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I am not saying I get all this because I don't but I have some common sense... and if you read the comments at the bottom you are  going to be entertained... or furious maybe.. depends on your take. 

 

I have never taken this drug but I took Effexor for 7 years. 

peace all

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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. Approximately 5% of all prescriptions for SSRIs involved coadministration with other antidepressants in an Australian sample (McManus et al., 2001), and in a recent Canadian study, the figure was 9% (Patten and Beck, 2004). Combinations may be the subject of medico-legal actions and allegations of professional misconduct. Some authorities continue to view the combination of TCAs with MAOIs as an appropriate treatment in special situations (Cowen, 2005). Recent new data about serotonin syndrome (SS), now usually referred to as serotonin toxicity (ST), indicate clearly which TCAs are risky in combination with MAOIs (Gillman, 2006a).

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014120/#bib42

 

I took effexor and celexa at the same time whined about ss at pp and got the smack down. but that is history... understanding of ss has changed since then

 

"A brief summary of TCA general pharmacology is given below, but for a detailed review see Rudorfer and Potter (1999). The structures of all antidepressants are available via PubChem (see websites)."  

in case you want to look

 

The main advances in our understanding of the TCA pharmacology relate to interactions with other drugs, especially interactions involving CYP450 enzymes, prediction of metabolism from genotyping and to the relative toxicity in overdose of individual drugs. Also, it has recently become possible to estimate what potency, at the serotonin and the noradrenaline transporters (SERT and NAT), is necessary for a drug to exhibit useful clinical effects.

 

"Nevertheless, what is clear from current toxicity data is that nortriptyline is less toxic than other TCAs and also than venlafaxine (the non-TCA SNRI antidepressant), both for complications following overdose and for overall deaths. The mortality from nortriptyline in overdose (5.5 deaths per million scripts (CI 2.2–11.4)) is similar to that from SSRIs, and better than both dothiepin (53.3 (CI 50.5–56.1)) (Buckley, 2002Whyte et al., 2003)) and venlafaxine (13.2 deaths per million scripts (CI 9.2–18.5))."

 

I am cherry picking what I think is relevant to me.. you need to read it yourself. 

 

Sim SC, Risinger C, Dahl ML, Aklillu E, Christensen M, Bertilsson L, et al. A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther. 2006b;79:103–113. [PubMed]

 

I had a major drug reaction when taking ppi drugs and effexor off to the hosp I went. 

 

 Indeed, it has only recently been discovered that 18% of Swedes have an ultrarapid CYP450 2C19 isoform (Sim et al., 2006b), which is likely to cause therapeutic failures with the usual doses of CYP2C19 substrates, such as proton pump inhibitors and antidepressants. Current data and important links may be found on the home page of the ‘Human Cytochrome P450 (CYP) Allele Nomenclature Committee'; this website covers the nomenclature for polymorphic alleles of CYP isoforms (Sim and Ingelman-Sundberg, 2006a).

 

ok it is getting too personal now and maybe I should move the rest of how it affects me personally to my own thread 

peace all

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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TCAs are less troublesome than the SSRIs in relation to CYP450 interactions. Indeed, of the SSRIs, Preskorn has suggested that fluoxetine and fluvoxamine, ‘… would likely not be approved today for this reason and should be used cautiously, if at all' (Preskorn and Flockhart, 2006a), and other authors have made similar comments (Gillman, 2005a). Just one-tenth of the minimum recommended dose (100x2009.gifmg) of fluvoxamine (i.e., 10x2009.gifmg) significantly inhibits caffeine metabolism via CYP450 1A2 (Christensen et al., 2002). Most SSRIs inhibit the metabolism of many other commonly used drugs via CYP450 enzymes to a clinically significant extent

 

a couple of tables you might like

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014120/table/tbl3/

 

 

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014120/table/tbl4/

 
I tried but was not allowed to post the charts they are well worth looking at. 

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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