Genetics and SSRIs

[Guest guest]

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