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Meyer, 2004 Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study.

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dcrmt

They have actually fit curves for SERT occupancy vs oral dose and vs blood concentration for each of the drugs tested.

Am J Psychiatry. 2004 May;161(5):826-35.
Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study.
Meyer JH1, Wilson AA, Sagrati S, Hussey D, Carella A, Potter WZ, Ginovart N, Spencer EP, Cheok A, Houle S.

Abstract http://www.ncbi.nlm.nih.gov/pubmed/15121647
 
The full paper is available here: http://ils.unc.edu/bmh/neoref/this.dir.unneeded/schizophrenia/review/tmp/352.pdfand http://www.mediafire.com/view/f3h1ao5ijfj93/papers#0yp2c8pbjrziaab (PDF)

Discussion here http://survivingantidepressants.org/index.php?/topic/6036-why-taper-paper-demonstrates-importance-of-gradual-change-in-plasma-concentration/
 
OBJECTIVE:
Minimum therapeutic doses of paroxetine and citalopram produce 80% occupancy for the serotonin (5-HT) transporter (5-HTT). The authors used [(11)C]DASB positron emission tomography to measure occupancies of three other selective serotonin reuptake inhibitors (SSRIs) at minimum therapeutic doses. The relationship between dose and occupancy was also investigated.

METHOD:
Striatal 5-HTT binding potential was measured in 77 subjects before and after 4 weeks of medication administration. Binding potential is proportional to the density of receptors not blocked by medication. Subjects received citalopram, fluoxetine, sertraline, paroxetine, or extended-release venlafaxine. Healthy subjects received subtherapeutic doses; subjects with mood and anxiety disorders received therapeutic doses. Percent reduction in 5-HTT binding potential for each medication and dose was calculated. To obtain test-retest data, binding potential was measured before and after 4 weeks in six additional healthy subjects.

RESULTS:
Substantial occupancy occurred at subtherapeutic doses for all SSRIs. Compared to test-retest data, each drug at the minimum therapeutic dose had a significant effect on striatal 5-HTT binding potential. Mean occupancy at this dose was 76%-85%. At higher plasma SSRI concentrations, 5-HTT occupancy tended to increase above 80%. For each drug, as the dose (or plasma level) increased, occupancy increased nonlinearly, with a plateau for higher doses.

CONCLUSIONS:
At tolerable doses, SSRIs have increasing occupancy with increasing plasma concentration or dose. Occupancy of 80% across five SSRIs occurs at minimum therapeutic doses. This suggests that 80% 5-HTT blockade is important for therapeutic effect. Occupancy should be measured during development of antidepressant compounds targeting the 5-HTT.
 
 
 
Chart from the paper:
http://www.mediafire.com/view/f3h1ao5ijfj93/papers#0yp2c8pbjrziaab

Edited by Altostrata
corrected link

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Barbarannamated

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Altostrata

As our member Rhi said:

 

....

When you open the document go to page 4 and look at the charts. You will see that at lower doses you must taper EXTRA slow, not faster. At higher doses, when you cut 1 mg, it only reduces your receptor occupancy by a small amount; but from 1 mg down to 0 you drop from 20% occupancy straight down to zero!

 

That's why we say calculate your cuts based on 10% of your CURRENT dose. (Or a smaller percentage....

....

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btdt

Any ideas how this would react in cold turkey?

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Altostrata

Cold turkey would cause a precipitous drop.

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btdt

I think I went on and off antidepressant drug BIG 60mg of prozac as a starting dose... and then the effexor 150 mg and 40mg of celexa... no idea why I went off celexa all by myself... but I did a year before I quit  the effexor fiasco... my poor brain 

It is amazing that I have healed as much as I have. 

What you will find in Grace Jacksons books 

more of the same more studies nobody seems to know about or that is what I suspect as I can't seem to get myself to a place to read the books... I hope somebody else reads them they have been out for years and I have seen little about her or her books.

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Altostrata

Some occupancy rate data for paroxetine and venlafaxine (Effexor) from
 
Neuropsychopharmacology (2008) 33, 3201–3212; doi:10.1038/npp.2008.47; published online 16 April 2008
Estimates of Serotonin and Norepinephrine Transporter Inhibition in Depressed Patients Treated with Paroxetine or Venlafaxine
Michael J Owens1, Stan Krulewicz2, Jeffrey S Simon3, David V Sheehan4, Michael E Thase5, David J Carpenter2, Susan J Plott1 and Charles B Nemeroff1
 
Link above will download pdf. The relevant chart in the paper is:

 

08_owens_parox_venla.jpg

Edited by Altostrata
updated link

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btdt

I don't get it so tried to figure something out from their words... 

"Although not a primary design of the study, no differences were observed between the magnitude of NET inhibition and patient response in subjects who completed the study; however, it was of interest that all five of the paroxetine-treated subjects who had >60% NET inhibition attained remission (Figure 4). The value of this observation is unclear as it was not fully replicated in the venlafaxine-treated subjects." 

 

Paxil works better then Effexor?  is that all they are trying to say.. I know this is not fair of me I need to apply myself I just can't now but still want to know... tired out. 

 

I did take a look at the ...almost as long as the article  seems to be a finger in every pie.

 

DISCLOSURE/CONFLICT OF INTEREST

Dr Owens: In the past 3 years, Dr Owens has had research grants from Eli Lilly, Pfizer, GlaxoSmithKline, Merck, Lundbeck, Cyberonics, and Johnson & Johnson. He has consulted to Pfizer, Lundbeck, Sepracor, Johnson & Johnson, Sanofi-Aventis, Forest Labs and received speaker's honoraria from GlaxoSmithKline. Dr Owens has a patent entitled ‘A method to estimate transporter occupancy’.

Mr Krulewicz and Dr Carpenter are employees of GlaxoSmithKline and own company stock.

Jeffrey S Simon, M.D. is a member of the GlaxoSmithKline and Wyeth Pharmaceuticals Speaker Bureaus. He has had clinical trial grant support from GlaxoSmithKline, Wyeth Research, Pfizer Pharmaceutical, Bristol Meyer Squibb, AstraZeneca, Eli Lilly, Cephalon, Sanofi, Organon, Sandoz, Merck, Upjohn Pharmacia, Otsuka, Synthelabo, and Forest Laboratories. Dr Simon has also served on advisory boards to Pfizer, Bristol Myers Squibb, Wyeth, Cephalon, Abbott and Tap Pharmaceuticals.

David V. Sheehan has had research support from Abbott Laboratories, American Medical Association, Anclote Foundation, Astra-Zeneca, Bristol-MyersSquibb, Cephalon, Eisai America, Inc., Eli Lilly & Company, Forest Laboratories, GlaxoSmithKline, International Clinical Research (ICR), Janssen Pharmaceutica, Jazz Pharmaceuticals, Kali Duphar Laboratories Inc., Medicinova, Merck, NIH, Novartis Pharmaceuticals Corp., Pfizer, Quintiles, Sanofi-Aventis, Tampa General Hospital, TAP Pharmaceuticals, Worldwide Clinical Trials, and Wyeth-Ayerst Pharmaceutical Co. Dr Sheehan is a stock shareholder in Layton Bioscience and Medical Outcome Systems. Dr Sheehan received speakers honoraria from Abbott Laboratories, AstraZeneca, Boots Pharmaceuticals, Bristol-MyersSquibb, Charter Hospitals, Dista Products Company, Eli Lilly & Co., Excerpta Medica Asia, GlaxoSmithKline, Hospital Corporation of America, Human, ICI, Janssen Pharmaceutica, Kali-Duphar, Merck, Organon, Novo Nordisk, Pfizer Inc., Solvay Pharmaceuticals, TAP Pharmaceuticals TGH-University Psychiatry Center, and Wyeth-Ayerst Laboratories. In the past 3 years, Dr Sheehan has served as a consultant to Solvay Pharmaceuticals, Avera Pharmaceuticals, MediciNova, Jazz Pharmaceuticals, Roche, Cephalon, GlaxoSmithKline, Sanofi-Synthelabo Research, AstraZeneca, Forest Laboratories, Pierre Fabre, Alza Pharmaceuticals, Bristol-MyersSquibb, Pfizer, National Anxiety foundation, Zars Pharma, Eisai, and Applied Health Outcomes/xCENDA.

Michael E Thase, M.D. serves on the Advisory Boards for AstraZeneca; Bristol-Myers Squibb Company; Cephalon Inc.; Cyberonics Inc.; Eli Lilly & Co.; GlaxoSmithKline; Janssen Pharmaceutica; MedAvante Inc.; Neuronetics, Inc.; Novartis; Organon Inc.; Sepracor Inc.; Shire US Inc.; Supernus Pharmaceuticals; Wyeth Pharmaceuticals, and is a member of the Speakers Bureaus for AstraZeneca; Bristol-Myers Squibb Company; Cyberonics Inc.; Eli Lilly & Co.; GlaxoSmithKline; Organon Inc.; Sanofi Aventis; Wyeth Pharmaceuticals. Dr Thase currently has equity holdings in MedAvante Inc., and receives royalty income from the American Psychiatric Publishing Inc., Guilford Publications, and Herald House. Dr Thase has no clinical trial grant support from the pharmaceutical industry.

Dr Nemeroff: In the past 3 years, Dr Nemeroff consulted to, served on the Speakers' Bureau and/or Board of Directors, has been a grant recipient, and/or owned equity in one or more of the following: Abbott Laboratories, Acadia Pharmaceuticals, American Foundation for Suicide Prevention (AFSP), American Psychiatric Institute for Research and Educations (APIRE), AstraZeneca, BMC-JR LLC, Bristol-Myers-Squibb, CeNeRx, Corcept, Cypress Biosciences, Cyberonics, Eli Lilly & Co., Entrepreneur's Fund, Forest Laboratories, George West Mental Health Foundation, GlaxoSmithKline, i3 DLN, Janssen Pharmaceutica, Lundbeck, National Alliance for Research on Schizophrenia and Depression (NARSAD), Neuronetics, NIMH, NFMH, NovaDel Pharma, Otsuka, Pfizer Pharmaceuticals, Quintiles, Reevax, UCB Pharma, and Wyeth-Ayerst.

Currently, Dr Nemeroff serves on the Scientific Advisory Board for Astra-Zeneca, Johnson& Johnson, Forest Laboratories, Quintiles, PharmaNeuroBoost and NARSAD. He is a grant recipient from NIH, NARSAD, and AFSP. He serves on the Board of Directors of AFSP, APIRE, NovaDel Pharmaceuticals, and the George West Mental Health Foundation. He owns equity in CeNeRx and Reevax. He owns stock or stock options in Corcept and NovaDel. Patents: ‘A method to estimate transporter occupancy’; ‘transdermal delivery of lithium’.

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Altostrata

Yes, these studies were mostly done for pharmaceutical firms to figure out dosing for the drugs.

 

What's important to us is the graphing, not the conclusions.

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btdt

Please explain how the graphing is important. What does it show ... as in conclusion is.  ?

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Altostrata

It shows the physiological effects of drugs at various dosages.

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btdt

How does it help us to know this?

Whatever knowing this is saying to you ...how does it help our understanding or us in withdrawal?

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Altostrata

Please read the discussion on SA -- link given in the first post.

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nz11

Looking at the graph for paroxetine (blue) #9 above.

Can we conclude the graph  doesnt reveal a great deal as we cant see whats happening below 12.5 mg [perhaps pharma doesnt want to show that area of the graph anyway...b'c maybe thats when the exponential decay occurs]...and above 12.5 it almost appears kind of linear 12.5,g has 30% sert and 25mg has pretty much 60% sert.

Perhaps its more complicated than this just realized the bottom graph is not dose per se but % net inhibition (?)so maybe its beyond me

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dcrmt

Interesting that the original link is broken now. I wonder if that's a coincidence due to the site's structure being changed, or the result of someone noticing it was getting an unusual number of hits.

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Altostrata

The site structure changed. I corrected the link in #1.

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Altostrata
On 5/9/2014 at 7:35 PM, Altostrata said:

Some occupancy rate data for paroxetine and venlafaxine (Effexor) from
 
Neuropsychopharmacology (2008) 33, 3201–3212; doi:10.1038/npp.2008.47; published online 16 April 2008
Estimates of Serotonin and Norepinephrine Transporter Inhibition in Depressed Patients Treated with Paroxetine or Venlafaxine
Michael J Owens1, Stan Krulewicz2, Jeffrey S Simon3, David V Sheehan4, Michael E Thase5, David J Carpenter2, Susan J Plott1 and Charles B Nemeroff1
 
Link above will download pdf. The relevant chart in the paper is:

 

08_owens_parox_venla.jpg

 

Updated the link in this post. It will download a pdf of the entire paper.

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