The Cytochrome P450 Genetic Test for Depression

Discussion in 'Fibromyalgia Main Forum' started by gapsych, Sep 23, 2010.

  1. gapsych

    gapsych New Member

    I found this on the Mayo Clinic Website. I wonder if the test could also be used for other medications.

    I have no idea if this test is only available at Mayo Clinic, whether it is accepted by the medical community, nor if insurance would cover something like this.

    Has anyone else heard about this?

    The Cytochrome P450 Genetic Test

    Over the past decade, the study of human genetics has shown how genetic factors influence a person's response to medications and their side effects. Mayo Clinic psychiatrists and laboratory medicine specialists developed a blood test (cytochrome P450) to pinpoint genetic factors that play a role in a person's response to various drugs, including most antidepressant medications. The test represents a major advance in providing the most appropriate depression drug treatment to meet each patient's needs.

    The cytochrome P450 blood test provides information on how a person's body metabolizes (breaks down) drugs. Genes are contained in each of the body's cells. They instruct the body to produce proteins that control how cells grow and function. This test identifies the gene or genes responsible for producing enzymes to metabolize these drugs.

    Certain patients may metabolize an antidepressant slowly. This can cause side effects or a toxic reaction, which may lead the patient to stop taking the drug. Others may metabolize the drug quickly, eliminating it from the body before they benefit from it. The cytochrome P450 test gives the doctor additional information to help choose the right antidepressant and the correct dose to reduce side effects for each patient.
  2. simonedb

    simonedb Member

    A friend of mine had a book about this called "mommies cry too" about someone's postpartem depression and the inability to pharmo treat it due to intolerance to meds and so finally mayo did this test on them to try to figure out what to do.

    I would love to get this test as I am sensitive to many medications and its hard to try tx for cfs due to that. I hadnt asked a doc to do it though so don't know if they would and if ins would pay, let us know if you find out please.
    [This Message was Edited on 09/23/2010]
  3. richvank

    richvank New Member

    Hi, gap and the group.

    The cytochrome P450 enzymes are used in phase 1 of the body's detoxication system, which processes drugs and toxins. The liver, kidneys, intestine, lungs and the olfactory epithelium in the nose are places where these enzymes are particularly active. Within the cells in these locations, they are located in the endoplasmic reticulum.

    All of us inherit unique sets of polymorphisms in our genes, including the genes that code for the CYP 450 enzymes. Some of these polymorphisms can affect how rapidly these enzymes catalyze detox reactions, and that can affect drug sensitivities, because it will affect how high the concentration of a drug rises for a certain dosage, and how long it stays in the body.

    The drug companies specify dosages based on an average of the general population. But if a person has polymorphisms in the particular enzymes that detox the drug, the specified dosage can be toxic to them. One way to look at drugs is that they are toxins that are attempted to be used at below their toxic levels. Unfortunately, for some drugs the therapeutic level is not far below the toxic level, even for people without the polymorphisms, but for a person with certain polymorphisms, some drugs are actually lethal at the usual prescribed dosage, and this problem contributes to the high rates of deaths from prescription drugs that are published once in a while.

    A few years ago, the FDA got serious about this problem, and started requiring the drug companies to report which enzymes are used to detox their particular drugs. This is now printed in the package inserts for the newer drugs. That put the onus on the physicians to evaluate the patient's polymorphisms, and removed a cause for litigation against the drug companies. So now the conventional medical labs offer tests to characterize these polymorphisms in (I think) three of the CYP 450 enzymes. These are the ones used to detox most of the drugs. I don't know whether the insurance companies will pay for these tests or not, but probably they will, because they could head off more costly problems.

    I might note that Genova Diagnostics (a specialty lab) has been offering the Genovations Detoxigenomic Profile for many years. It evaluates polymorphisms in eight of the CYP 450 enzymes, as well as in several other detox-related enzymes in Phase 2 of the detox system.

    I have seen results of this profile for quite a few PWCs, and there are commonly several polymorphisms present. This profile is not cheap, but the results can guide the use of drugs as well as avoidance of certain environmental toxins. They can also sometimes shed light on the reasons a particular person became ill.

    Best regards,

  4. gapsych

    gapsych New Member

    I just found the following at

    Now I am confused. Why would Mayo Clinic be offering something that has not been studied enough to actually use as a diagnostic tool. Maybe it is still in the research stage?

    Looks like there need to be more studies before this test becomes routine.


    Structured Abstract

    Objectives: To determine if testing for cytochrome P450 (CYP450) polymorphisms in adults
    entering selective serotonin reuptake inhibitor (SSRI) treatment for non-psychotic depression
    leads to improvement in outcomes, or if testing results are useful in medical, personal, or public
    health decisionmaking.

    Data Sources:
    We searched MEDLINE®, the Cochrane Database of Abstracts of Reviews of
    Effects, PsychInfo, HealthSTAR, and CINAHL, and reviewed the reference lists of included
    articles and relevant review articles and meta-analyses for eligible studies. We also included
    documents from the U.S. Food and Drug Administration (FDA) that could be publicly accessed.

    Review Methods: We developed an analytic framework and identified key questions to guide
    the review process. Project-specific inclusion/exclusion criteria were also developed and were
    used by paired researchers independently to review both abstracts and full-text articles; both
    researchers were required to agree on inclusion status at the full-text stage. Abstractors
    evaluated each included article for factors affecting internal and external validity.

    Results: A review of 1,200 abstracts led to the final inclusion of 37 articles. The evidence
    indicates the existence of tests with high sensitivity and specificity for detecting only a few of the more common known polymorphisms of 2D6, 2C19, 2C8, 2C9, and 1A1. There is mixed
    evidence regarding the association between CYP450 genotypes and SSRI metabolism, efficacy,
    and tolerability in the treatment of depression, mainly from a series of heterogeneous studies in
    small samples. There are no data regarding:

    (a) if testing for CYP450 polymorphisms in adults
    entering SSRI treatment for non-psychotic depression leads to improvement in outcomes versus not testing, or if testing results are useful in medical, personal, or public health decisionmaking;

    (b) if CYP450 testing influences depression management decisions by patients and providers in
    ways that could improve or worsen outcomes; or (c) if there are direct or indirect harms
    associated with testing for CYP450 polymorphisms or with subsequent management options.

    Conclusions: There is a paucity of good-quality data addressing the questions of whether testing for CYP450 polymorphisms in adults entering SSRI treatment for non-psychotic depression leads to improvement in outcomes, or whether testing results are useful in medical, personal, or public health decisionmaking.

    Edited to break paragraphs for easier reading.
  5. amomwithsickkids

    amomwithsickkids New Member

    I remember reading about the p450 pathway and diflucan as it relates to lyme. Had no idea there was a test for it, but would bet the farm it won't be covered by insurance any time soon. Too bad because maybe the results could help guide treatment as jam338 mentioned and people could get a better handle on their individual issues. Being a guinea pig gets old after awhile.

    Thanks gapsych for bringing this up.

  6. richvank

    richvank New Member

    Below is a transcript of Dr. Topol's post on Pharmacogenomics and Consumers. We look forward to your feedback.

    We're back to one of our favorite topics, and that is consumer genomics. This is about many different articles that have come out in recent days and weeks post the Government Accountability Office, Congressional Reviews, and FDA on the various consumer genomic companies, along with a piece I had on the pharmacy benefit managers, pharmacies, and the whole issue of pharmacogenomics.

    In essence, what's occurred at this point is that the consumer genomics companies need to get their act together to have uniform standards so there's consistency for high-throughput genotyping that cuts across the four major players -- that is, deCODE, 23andMe, Navigenics, and Pathway Genomics. That probably will occur, and that call, such as the Nature editorial for uniform standards of what constitutes susceptibility [based on] criteria from the literature (not the genotyping, which is accurate), appears to be quite warranted.

    Now there's another area that I think is quite interesting and that is, of course, the pharmacogenomic side. For example, Pathway [Genomics], and I actually put out my data from their report, in the recent Science Translational Medicine commentary. Getting the data for drugs like Plavix and many others [such as] warfarin that have established incontrovertible links between particular gene variants and effects of the drug -- be it avoidance of major side effects or appropriate dose or even lining up with the right medication -- this appears to be useful, and this is where perhaps there's been the most progress in the ten years since the draft human sequence was available.

    When Pathway [Genomics] was going to put this out in Walgreen’s and then subsequently later in the summer at all CVS drugstores, they were going to have this pharmacogenomic panel for $79, which is not such a bad deal when you think that even a one-off genotype for things like CYP2C19 for Plavix costs well over $100 and this one gives more information.

    It looks as though there may be a place for consumer genomics -- very different from disease susceptibility -- that is giving a readout for the currently available gene/prescription drug interactions, of which there are many, many important ones. This is quite interesting different situation for consumers. Many people, when they're asked about do they want to have disease susceptibility data, they don't appear particularly keen and eager because they're fearful or they're uncertain about what that data actually means. That's been reinforced by these recent governmental regulatory reviews. On the other hand, the data for prescription medication/gene interactions appears to be uniformly of interest to consumers. Let's see if there's a way to go forward where, if this data does become available, that it becomes inexpensive and hopefully part, someday, of the routine way that we can try to avoid major side effects and also line up appropriate drugs and doses -- right patient, right medication.

    I'll be very interested in your thoughts. And if you haven't taken a look at the Science Translational Medicine piece, it's also interesting how pharmacy benefit managers, both Medco and CVS Caremark -- which together account for over a hundred million Americans’ prescription benefits -- how they're seizing this opportunity because otherwise it's not being really pursued. Thanks very much for your attention.
  7. gapsych

    gapsych New Member

    This is interesting. I am looking for updates on this.

    Would this also apply to Mayo Clinic?

    FDA Warns Consumer Genomics Firms, Illumina on Selling Unapproved Dx Products
    June 11, 2010

    NEW YORK (GenomeWeb News) – The US Food and Drug Administration has sent letters to four consumer genomics services providers and Illumina saying that it believes the firms are selling unapproved diagnostic devices.

    The agency sent letters yesterday to Knome, 23andMe, Decode Genetics, and Navigenics. Illumina also received a letter because Decode and 23andMe use the firm's Infinium HumanHap550 arrays in providing genetic information to their customers.

    The letters are very similar in their message to the firms that FDA believes they are using products "intended for use in the diagnosis of disease or other conditions." It cited Knome's KnomeComplete offering, 23andMe's Personal Genome Service, Decode Genetics' Decodeme Complete Scan, and Navigenics' Health Compass as not having regulatory clearance.

    The FDA has told the firms that they should "take prompt action" to reply to the agency. "If you would like to meet with us to discuss whether there are tests you are promoting that do not require review by FDA and what information you would need to submit in order for your product to be legally marketed for the other uses, let us know and we will schedule a meeting with you," the agency wrote in the letters.

    "23andMe is in receipt of the FDA's letter and will respond directly to the agency," 23andMe said in a statement today. "It is important to note that we disagree with the FDA's conclusion. Regardless, we have always been open to discussions to formulate a rational way to regulate the personal genetics industry, and we look forward to continuing those discussions with the FDA."

    The letters are the latest action taken by FDA to crack down on direct-to-consumer genetic test offerings that it believes are in violation of regulations. Recently, the agency sent a letter to Pathway Genomics informing the firm that its genetic testing kit requires marketing clearance from the agency. The firm had inked a deal with pharmacy chain Walgreens to sell a collection kit for the DTC test product, but Walgreens subsequently put the deal on hold following the FDA's letter.

    The FDA's action spurred the US Congress to open an investigation into DTC genomics providers. The House Committee on Energy and Commerce sent letters to three firms — PATHWAY GEONOMICS (my bold), 23andMe, and Navigenics — requesting information on several aspects of the tests they sell directly to the consumer, including the specific diseases and drugs for which the services provide genomic risk data; policy documents and materials on genetic counseling or physician consultation; data showing the accuracy of the risk predictions delivered by these services; details on policies regarding handling of DNA samples; as well as documents relating to the services' compliance with FDA regulation.

    The FDA has yet to any formal guidelines specific to DTC genomics firms, but it has always said it has the authority to regulate these services.

  8. richvank

    richvank New Member

    Hi, gapsych.

    I don't think the controversy applies to what Mayo Lab does about measuring the CYP 450 polymorphisms. The LabCorp test menu includes polymorphism tests on CYP 2C9, 2C19, and 2D6.

    The issue that's being debated is whether gene characterization kits should be sold directly to consumers, rather than requiring that they be ordered through physicians.

    The larger issue involves the sale of complete genome polymorphism characterizations directly to consumers. Should this be allowed? Should it be regulated? Can people be trusted not to react in some bad way to knowing their polymorphisms? Are the companies who are doing this giving accurate interpretations of the probabilities of developing one condition or another based on a person's polymorphisms? Is enough really known to give accurate estimates of these probabilities? and so on.

    I think that some of the polymorphisms really are indicative of sensitivities to one thing or another, and I have used these data quite a bit in analyzing individual cases. It can help people to know which drugs they should avoid, or should take in smaller dosages. Also, if they should avoid certain things, such as permanent hair dyes or various kinds of smoke and vehicle exhaust.

    Best regards,

  9. simonedb

    simonedb Member

    hey thanks for clearing that up Rich, that is what my cynical mind was figuring.......
  10. gapsych

    gapsych New Member

    My cynical mind has concluded that there needs to be standardization before/if released to the public. I guess I will go with the FDA recommendations.

    As for selling them directly to consumers, I did not think of the drawbacks to doing this. I think it should be through a medical doctor. Now it makes sense why Mayo Clinic can do this.

    This is a very interesting topic.