Tag: HTR2A

I think this is a very important topic. There is now sufficient evidence to indicate that people with specific variations of genes CYP2D6, SLC6A4, and HTR2A, are unlikely to respond to SSRIs. The evidence indicates that especially Caucasian females are unlikely to respond to SSRIs, if they have the genes SLC6A4 S/S and HTR2A G/G. Evidence also shows that they may not respond to SNRIs as well.

If you are in this population, I wonder if your psychiatrist spoke to you about this. I think it’s a pretty big deal, given the sufficient evidence for Caucasians.
I am an Eastern European female, and I had no response at all to any SSRIs or SNRIs, or any medication in general so far. I had trials of mirtazapine, sertraline, abilify, latuda, risperidone, olanzapine, fluoxetine, pristiq, cymbalta, and seroquel. I was then referred to a more specialized psychiatric hospital, and they performed genetic testing for me. The results indicated that I have SLC6A4 S/S and HTR2A G/G genes. The medical records state the following:

SLC6A4 S/S
Homozygous for the short promoter polymorphism of the serotonin transporter gene. The short promoter allele is reported to decrease expression of the serotonin transporter compared to the homozygous long promoter allele. The patient may experience a delayed response with selective serotonin reuptake inhibitors, or may benefit from non-selective antidepressants.

HTR2A G/G
Homozygous variant for the G allele for the serotonin receptor type 2a. Two copies of the G allele. This genotype has been associated with an increased risk of adverse drug reactions with certain selective serotonin reuptake inhibitors.

CYP2D6 intermediate metabolizer – Higher plasma concentrations may increase the probability of side effects. Consider a lower starting dose and slower titration schedule as compared with normal metabolizers.

I think given that I have not responded to any of the medications (each one was tried for over 8 weeks), and these test results, it’s pretty clear that I am very unlikely to respond to any other SSRIs or SNRIs. I had a very good neuropsychiatrist at the psychiatric hospital, but unfortunately I was transferred to another hospital due to pregnancy. Now I have a psychiatrist who is a resident, so she does not have a lot of experience. I was prescribed lamotrigine and fluoxetine. I think the lamotrigine makes sense, given that I have no tried it, but she only gave me 25mg per day. I don’t think the fluoxetine makes sense, because it’s an SSRI, and I have already tried it. I also stopped sleeping starting the first day I began to take it. I have been sleeping only 3-4 hours a day since I started it 8 days ago.

I wonder if anyone had a good doctor who discussed with them genetic testing and what were their suggestions? What are the options if there is no response to SSRIs and SNRIs? I don’t think my resident psychiatrist has enough experience in this.