Re: Genetics and SSRIs

[Guest guest]

Here is an interesting review I found. I emailed the author last night to see

if he knows about PSSD and would be interested in doing a study on it.

http://www.mdpi.com/1424-8247/3/12/3614/

Pharmacogenetics of SSRIs and Sexual Dysfunction

Liana Osis and R. Bishop *

Department of Pharmacy Practice, College of Pharmacy, University of Illinois at

Chicago, 833 S. Wood St. Rm. 164 (M/C886), Chicago, IL 60612, USA

* Author to whom correspondence should be addressed.

Received: 1 November 2010; in revised form: 30 November 2010 / Accepted: 9

December 2010 / Published: 15 December 2010

(This article belongs to the Special Issue Antidepressants)

Download PDF Full-Text [74 KB, uploaded 15 December 2010 11:11 CET]

Abstract: Sexual dysfunction (SD) is a common and disconcerting side effect of

selective serotonin reuptake inhibitors (SSRIs) that often influences a

patient's desire to continue long-term antidepressant treatment. Studies

specifically assessing changes in sexual well-being over time illustrate that

the incidence of sexual side effects from SSRIs ranges from 20% to 70%,

depending on the characteristics of the study sample assessed. Developing

strategies to predict who may be at the highest risk for adverse changes in

their sexual well-being is an important step in improving the quality of life

and treatment of patients who require antidepressant therapy. Pharmacogenetic

studies of SSRI-associated SD have identified associations between serotonin and

glutamate system genes with aspects of SD. The results of studies investigating

genetic variations in drug metabolism enzymes and their relationships to

antidepressant-associated adverse effects have been mixed. Continued efforts to

characterize the relationships between genetic markers and antidepressant

outcomes, and to translate this knowledge to patient care, have the potential to

significantly improve the empiric selection of antidepressant agents and to

minimize the risk for intolerable side effects.

You can read more about the author here

http://ccm.psych.uic.edu/People/Investigators/bishop.aspx

He is a professor specializing in the pharmacogenetics of psychiatric drugs.

Basically trying to figure out the genetics of what I believe to be true. For

some people SSRIs work (probably a minority), for many they do nothing, and for

a decent percentage they have intense side effects like sexual dysfunction. It

is my honest hope that in the future pharmacogenomics will make it such that

people can know ahead of time how they will respond to a drug and not take it if

its likely to cause side effects like PSSD.

>

> Hey everyone,

>

> I just posted a response to someone on this but I felt it was relevant. I

think the reason SSRIs work in large clinical studies but only barely is because

of genetic variation between people. There was a genome wide association study

done on SSRI response. They found a specific allele of the gene ABCB1 involved

in blood brain barrier transport to be highly beneficial to the chances SSRIs

would work. In this case more than 7 times more likely to work if someone has a

C allele. In most human populations the C allele though is the minor allele,

meaning most people don not have it. I actually said something wrong in my

previous response post. 70% of people don't even have one C allele.

>

> My hopthesis is 70% of people SSRIs don't work at all. Maybe for 30% they

have some efficacy. This would explain why clinical trials show questionable

results. Only 30% of people in the trial benefit. Enough to demonstrate some

effectiveness but while in reality the drugs don't work for most people.

>

> Here is the post from SNPedia.

>

> rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which

encodes a protein that transports certain molecules across the blood-brain

barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of

certain drugs and thus their efficacy or potential for adverse side effects.

rs2032583 is one of 9 SNPs found within a tight linkage block (r2 >= 0.8 ) such

that the minor allele at any one of them predicts (with ~80%+ accuracy) that the

other SNPs will also be the minor allele. The list of the 9 SNPs is shown below.

> When treated for depression with substrates of the protein encoded by ABCB1,

carriers of one or two minor alleles at these ABCB1 SNPs have been reported to

respond better than non-carriers. The antidepressant drugs that are known to be

substrates include citalopram, paroxetine, amitriptyline, and venlafaxine. The

relative odds of better response for rs2032583© carriers is 7.72 (CI:

2.8-21.3, p=0.000065) based on a study of ~400 primarily Caucasian

patients.10.1016/j.neuron.2007.11.017

> The 9 SNPs in the linkage block identified are 10.1016/j.neuron.2007.11.017:

>

>

> Let me know if you have any questions. I'll answer what I can. Go to the

SNPedia page for more info. They have nice graphics etc.

>

> http://www.snpedia.com/index.php/Rs2032583

>

[Guest guest]

This is weird for me to read. I developed instant serious sexual side effects

but also, prozac really really 'worked' for me. For the few months that I was

on it I felt 'good' all the time. People told me I seemed to be doing great all

of a sudden (they had no idea why) - sexuality vanished into thin air but I

didn't care since I assumed it would return. I've always thought my experience

was pretty common for PSSD victims, but I guess not.

>

> Hey everyone,

>

> I just posted a response to someone on this but I felt it was relevant. I

think the reason SSRIs work in large clinical studies but only barely is because

of genetic variation between people. There was a genome wide association study

done on SSRI response. They found a specific allele of the gene ABCB1 involved

in blood brain barrier transport to be highly beneficial to the chances SSRIs

would work. In this case more than 7 times more likely to work if someone has a

C allele. In most human populations the C allele though is the minor allele,

meaning most people don not have it. I actually said something wrong in my

previous response post. 70% of people don't even have one C allele.

>

> My hopthesis is 70% of people SSRIs don't work at all. Maybe for 30% they

have some efficacy. This would explain why clinical trials show questionable

results. Only 30% of people in the trial benefit. Enough to demonstrate some

effectiveness but while in reality the drugs don't work for most people.

>

> Here is the post from SNPedia.

>

> rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which

encodes a protein that transports certain molecules across the blood-brain

barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of

certain drugs and thus their efficacy or potential for adverse side effects.

rs2032583 is one of 9 SNPs found within a tight linkage block (r2 >= 0.8 ) such

that the minor allele at any one of them predicts (with ~80%+ accuracy) that the

other SNPs will also be the minor allele. The list of the 9 SNPs is shown below.

> When treated for depression with substrates of the protein encoded by ABCB1,

carriers of one or two minor alleles at these ABCB1 SNPs have been reported to

respond better than non-carriers. The antidepressant drugs that are known to be

substrates include citalopram, paroxetine, amitriptyline, and venlafaxine. The

relative odds of better response for rs2032583© carriers is 7.72 (CI:

2.8-21.3, p=0.000065) based on a study of ~400 primarily Caucasian

patients.10.1016/j.neuron.2007.11.017

> The 9 SNPs in the linkage block identified are 10.1016/j.neuron.2007.11.017:

>

>

> Let me know if you have any questions. I'll answer what I can. Go to the

SNPedia page for more info. They have nice graphics etc.

>

> http://www.snpedia.com/index.php/Rs2032583

>

[Guest guest]

I hope you eventually unravel the mystery, Justn, but just for the

record, drug companies only have to show that a drug is more effective

than a placebo in two trails but it doesn't matter how many trails they

have to do to get this result. What this means is that drug companies

just keep re-doing trails until they get two positive results. Trail one

might be positive and trail 30 might be positive but all the others

inbetween would have shown negative, but that doesn't matter apparently.

If 9% are supposed to be good responders to medication then this would

show up to be significant in drug trails but it isn't as most trails

show no benefit. And what is this so called benefit anyway? About 1 or 2

pounts on the Hamilton scale, which is not very impressive. So in other

words the risk greatly outway any benefits by a long shot. Well, that's

my experience.

But it gets worse, if you use an active placebo there will be no

difference between this and the antidepressant used in drug trails, so

you have to ask yourself is it worth doing a genetic test to see if you

are a good responder when you can just take an active placebo and get

the same benefit but with far less risk.

But there is another problem and I wrote to Irvin Kisrch (author of the

Emporers New Drugs, The Antidpressant Myth) about it. I said to him that

as these drugs appear to induce chronic depression is some people (and

it might actually be a lot of people that are affected) then eventually

these people will feed through into drug trails and may appear to be

good responders when in fact all they are doing is just satifying a

biological need that was set up by their previous use of antidedressant

drugs. Irvin wrote back and thanked me for that concern and said he

would be looking into it.

I hope you don't get too angry with me, , as I see that you are

earnest, mean well, and love science. I shant go into any further

debate about this as it won't change anything. I will leave it to

people on this list to make up their own minds.

Kv

>

> Hey everyone,

>

> I just posted a response to someone on this but I felt it was

relevant. I think the reason SSRIs work in large clinical studies but

only barely is because of genetic variation between people. There was a

genome wide association study done on SSRI response. They found a

specific allele of the gene ABCB1 involved in blood brain barrier

transport to be highly beneficial to the chances SSRIs would work. In

this case more than 7 times more likely to work if someone has a C

allele. In most human populations the C allele though is the minor

allele, meaning most people don not have it. I actually said something

wrong in my previous response post. 70% of people don't even have one C

allele.

>

> My hopthesis is 70% of people SSRIs don't work at all. Maybe for 30%

they have some efficacy. This would explain why clinical trials show

questionable results. Only 30% of people in the trial benefit. Enough to

demonstrate some effectiveness but while in reality the drugs don't work

for most people.

>

> Here is the post from SNPedia.

>

> rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene),

which encodes a protein that transports certain molecules across the

blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral

concentrations of certain drugs and thus their efficacy or potential for

adverse side effects. rs2032583 is one of 9 SNPs found within a tight

linkage block (r2 >= 0.8 ) such that the minor allele at any one of them

predicts (with ~80%+ accuracy) that the other SNPs will also be the

minor allele. The list of the 9 SNPs is shown below.

> When treated for depression with substrates of the protein encoded by

ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have

been reported to respond better than non-carriers. The antidepressant

drugs that are known to be substrates include citalopram, paroxetine,

amitriptyline, and venlafaxine. The relative odds of better response for

rs2032583© carriers is 7.72 (CI: 2.8-21.3, p=0.000065) based on a

study of ~400 primarily Caucasian patients.10.1016/j.neuron.2007.11.017

> The 9 SNPs in the linkage block identified are

10.1016/j.neuron.2007.11.017:

>

>

> Let me know if you have any questions. I'll answer what I can. Go to

the SNPedia page for more info. They have nice graphics etc.

>

> http://www.snpedia.com/index.php/Rs2032583

>