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Wednesday, June 29, 2016

In the genes?




I'm starting to look into genetic testing to help my work with patients who have not responded well to multiple psychotropic medications. It feels like a desperate bid, but I'm not sure what other help I can offer.

There are three main testing products, that I could find:

Genesight

Genecept Assay

and

Genelex


I have three main questions about these products:

1. What do they tell me?

2. How accurate/helpful are they?

3. How easy are they to use?


Genesight

Genesight seems to be the one mentioned most by people I asked. Practically speaking, it involves a buccal swab sent to Genesight via prepaid FedEx, with access to results online 36 hours after the sample is received. They are covered by some insurance plans, and have a financial assistance program. And it looks like, in order to try out the test, you need to speak with one of their representatives-there's no way to order online.

In terms of how well it works, their claim is, "Patients with uncontrolled symptoms who switch off of genetically discordant medications show the greatest reduction in depressive symptoms."

They also claim that, "70% of patients who have failed at least one medication are currently taking a genetically sub-optimal medication," and that, "GeneSight testing may help avoid drug-drug interactions and compounding side effects."

Finally, for patients younger than 18, Genesight can help in decisions about efficacy, tolerability, and dosing.

They site a paper, A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder, the results of which were:

Between-group trends were observed with greater than double the likelihood of response and remission in the GeneSight group measured by HAMD-17 at week 10. Mean percent improvement in depressive symptoms on HAMD-17 was higher for the GeneSight group over TAU (30.8% vs 20.7%; p=0.28). TAU subjects who had been prescribed medications at baseline that were contraindicated based on the individual subject's genotype (i.e., red bin) had almost no improvement (0.8%) in depressive symptoms measured by HAMD-17 at week 10, which was far less than the 33.1% improvement (p=0.06) in the pharmacogenomic guided subjects who started on a red bin medication and the 26.4% improvement in GeneSight subjects overall (p=0.08).

You'll notice that they talk about "trends" without any statistics, and mean percent improvement showed no significant difference (p=0.28), even though they point out that improvement in the Genesight group was higher. Recall that p=0.28 means there is a 28% chance that the differences they found were due to chance alone.

The "red bin" is a reference to the way Genesight presents its results, which I find easy to understand, if not entirely illuminating. This is an example:




I don't get the impression that the results give me information about which drugs will be helpful, as much as which drugs won't be harmful.

How does the test work? Genesight measures polymorphisms among 5 genes, CYP2D6; CYP2C19; CYP1A2; the serotonin transporter gene, SLC6A4; and the serotonin 2A receptor gene, HTR2A.

The CYP genes are clearly measures of rates of metabolism. A repeat length polymorphism in the promoter of SLC6A4 has been shown to affect the rate of serotonin uptake. The implications of this fact are not clear to me, but according to Wikipedia, genetic variations in the SLC6A4 gene have resulted in phenotypic changes in mice, including increased anxiety. HTR2A influences serotonin transporter binding potential, and variations in the gene have been associated with variations in outcome in treatment with citalopram.

So the answers to my three questions, for Genesight, are:

1. It tells me which drugs are more and less safe and tolerable to use. And if I accept their conclusion that patients switched off red bin drugs improved significantly, then perhaps it tells me which drugs will be effective, but I'm skeptical about this part.

2. The results are less impressive than they'd like me to think.

3. Results are clear and easy to read.  Turnover time is good. Getting hold of a test is not that easy.



Genecept Assay

The genecept FAQ page is much more informative than the Genesight pages. The test can be ordered online or by phone. It's covered by most insurance and they have a patient assistance program. Turnaround time is 3-5 business days from receipt of the sample, also a buccal swab, and they provide expert staff to help interpret results.

The online order form also gives you the option of becoming a "Preferred Provider", which means they'll send patients who are looking for genetic testing to you.

As for function:

The Genecept Assay® report is intended to aid clinicians in making personalized treatment decisions tailored to a patient’s genetic background and helps to inform psychiatric treatments that:

Are more likely to be effective
Have lower risk for side effects and adverse events
Are dosed appropriately

The report consists of two pages, and looks like this:



So they look at more genes than Genesight, and they provide one report about what's safe to use, and another about what's potentially helpful.  And in all honesty, I don't have the energy right now to look up how believable their first page markers are in terms of efficacy, and I think I would need their help to interpret these results, but they do provide more information than Genesight.

Answers:

1. Safety, tolerability, and efficacy

2. I'm too tired to check

3. Easy to get the test, harder to interpret results


Genelex

Genelex allows you to order tests online, too. They claim there is some insurance coverage (See *, below), they have some fancy software that's supposed to be helpful, in addition to their report, and they have a 3-5 day turnaround time.

Genelex restricts itself to CYP450 genes, but it includes three that Genesight doesn't, 3A4, 3A5, and 2C9, but doesn't include 1A2. This is a link to a sample result, which is too long to include as an image. And like Genesight, it's mainly about what is and isn't safe or tolerable to take.*

*Actually, I just learned on the FAQ page that Genelex also includes CYP1A2; NAT2;DPD Enzyme; UGT1A1; 5HTT; and HLA-B*5701, but that these are generally not covered by insurance. I also couldn't figure out what data these additional tests provide.

Answers:

1. Safety, tolerability, maybe efficacy?

2. For the CYP tests, same as above, for others, I don't know

3. The software seems like overkill. The report is clear and moderately informative. You can order the test online.


That's it for this topic, for now, for me. I have yet to decide whether I'm going to use any testing.




1 comment:

  1. Great report on what's available.

    I usually restrict testing to people who give me a history of not tolerating antidepressants, but that is a significant number (about 1/6).

    I am also trying to get one of the major genotyping services to come up with a feature that allows rapid scanning of your own raw genotype data with their "browse raw data" feature. I might try that using the genotypes used in the commercial packages and see what happens.

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