Genetic testing: "Personalized medicine," liver enzymes, genotypes, GeneSightRx, Genomind, etc.

[nycdreamer]

I hear what you are all saying. These drugs really mess with us. I think there has to be something to the neurotransmitters though because I get severe ocd and depression whenever I come off an ssri- and revert back to my old problems. Sadly, these drugs mess with our entire systems though. Wonder if St. Johns Wort would help...

[Altostrata]

There is no question psychiatric drugs affect the nervous system. They don't "balance" anything, though.

 

Many people find antidepressants stimulating.

 

In the past, when you came off a drug, you might have done so too fast. Withdrawal symptoms themselves can manifest as obsessive thinking, etc. Or, the nervous system distress may have exacerbated a basic tendency in you.

[Piglet]

I had this testing and I am a poor metabolizer for CYP2D6 and CYP2C19. I am an intermediate activity for MTHFR. Because of this my pdoc gave me an rx supplement called Enlyte that is supposed to help with folic acid metabolism and serum folate levels and reduce my homocysteine levels.

I haven't taken any yet because I don't want to and another rx to the mix and I'm afraid of side effects.

[scot]

Hi all,

its the first time that our genome can be sequenced,interpreted under 1000$ with the Personal Genome Project.The very important issue is that the genome will be released on the internet,so as researchers can work on it,interpreted etc .I think its a good step forward for our issues.Here is the article

 

http://www.prnewswire.com/news-releases/veritas-genetics-breaks-1000-whole-genome-barrier-300150585.html

 

BOSTON, Sept. 29, 2015 /PRNewswire/ -- Veritas Genetics today announced that the company is making it possible for participants in the Personal Genome Project (PGP) to be among the first to get their whole genome sequenced and interpreted for less than a $1,000.

Led by Veritas Genetics Co-Founder Dr. George Church, Professor of Genetics at Harvard Medical School and Director of the Personal Genome Project, PGP is a long-term effort to sequence thousands of complete genomes to enable research into personal genomics andpersonalized medicine. PGP has more than 16,000 participants worldwide.

The "$1,000 Genome" has long been considered the tipping point when sequencing and interpreting the human genome becomes commonplace and begins to rapidly increase what is known and to dramatically impact healthcare. The catchphrase underscores how far science has come since the actual cost of the Human Genome Project, estimated at $2.7 billion spent over a decade.

Since then, others have touted the $1,000 genome, but never before has an organization been able to include interpretation, which is the key to applying genetic information into decisions about disease monitoring, prevention, nutrition, exercise, and more. "This is a true milestone worth celebrating, since it includes interpretation and genetic counseling," says Dr. Church.

Veritas Genetics' collaboration with PGP is a natural step. Three of the company founders have over 10 years of experience in processing and understanding whole genomes from their work with PGP. In addition to Dr. Church, Veritas Genetics' Chief Scientific Officer Preston Estep is PGP's Director of Sequencing, and Dr. Joseph Thakuria, the company's Chief Medical Officer, serves as PGP's Medical Director.

"Today's announcement is a watershed moment that will truly change the way we take care of ourselves and our families," says Mirza Cifric, Veritas Genetics' CEO and Founder. "While the cost of sequencing has dramatically declined, there is still a need for interpretation and information that is tangible and actionable to help individuals live better and longer lives. At Veritas, we are unlocking the potential of the $1,000 genome starting with early adopters, PGP participants. You can expect to see much more from us on this topic as we expand access beyond the PGP."

In June 2015, Veritas Genetics broke a similar barrier for breast and ovarian cancer by making its myBRCA genetic screening test of BRCA1 and BRCA2 available for $199. The myBRCA test showcases the range of genetic testing that Veritas Genetics will be offering, from specific panel tests through whole human genome sequencing. PGP participants are able to sign up with Veritas Genetics to have their whole genome sequenced at www.veritasgenetics.com/pgp.

About Veritas Genetics
Veritas Genetics is a global pioneer in disease prevention through accessible genetic information. By removing the barriers to genetic screening, Veritas empowers individuals and doctors to make informed lifestyle decisions that can lead to disease prevention and longer and healthier lives. Veritas is founded by leaders in genomics and operates globally from its offices in US, Europe and China. 
www.veritasgenetics.com.

[oskcajga]

The human genome product seems to have been regarded as having limited utility in modern medicine (i.e., generally a disappointment):

E.g.,

 

http://www.theguardian.com/commentisfree/2011/apr/17/human-genome-genetics-twin-studies

 

http://www.i-sis.org.uk/humangenome.php

 

http://www.nytimes.com/2010/06/13/health/research/13genome.html?pagewanted=all&_r=0

 

http://www.scientificamerican.com/article/revolution-postponed/

 

http://www.thedailybeast.com/articles/2013/01/29/the-selfish-gene-the-broken-promises-of-the-human-genome-project.html

 

That may change some day, but as it currently stands the knowledge of our genes has relatively limited utility compared to the promises that were made at the onset of the project.  That being said, it would still be very interesting to take a look at my genome and to pay someone to interpret the results.  This latter point of paying someone to interpret the results is the most important, because just having  a bunch of nucleotide sequences on a 6000000 page excel spreadsheet is next to useless unless it's compared against known patterns by an expert in the field.

 

Just some thoughts.

[Altostrata]

The connection of a particular genetic pattern to any specific disease has been accomplished for only a very few narrowly defined illnesses, such as some forms of breast cancer.

 

Other than that, getting your genome mapped is an academic exercise for the curious.

 

As explained in great detail above, regarding drugs, genetic analysis can indicate only where you might have metabolism difficulties possibly resulting in increased adverse effects. It will NOT predict which psychiatric drugs will "work," meaning alleviate your symptoms (depression, anxiety, etc.). It will NOT predict withdrawal difficulties, nor explain why some people have worse withdrawal syndrome than others.

[Meimeiquest]

I think the genome project has been very helpful in one respect...it's how we have learned about the importance of epigenetics.

[Altostrata]

British Journal of Clinical Pharmacology. 2012;74(4):698-721. doi:10.1111/j.1365-2125.2012.04328.x.
Personalized medicine: is it a pharmacogenetic mirage?
Shah RR, Shah DR.
 
Abstract and free full text at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477339/

Abstract

The notion of personalized medicine has developed from the application of the discipline of pharmacogenetics to clinical medicine. Although the clinical relevance of genetically-determined inter-individual differences in pharmacokinetics is poorly understood, and the genotype-phenotype association data on clinical outcomes often inconsistent, officially approved drug labels frequently include pharmacogenetic information concerning the safety and/or efficacy of a number of drugs and refer to the availability of the pharmacogenetic test concerned. Regulatory authorities differ in their approach to these issues. Evidence emerging subsequently has generally revealed the pharmacogenetic information included in the label to be premature. Revised drugs labels, together with a flurry of other collateral activities, have raised public expectations of personalized medicine, promoted as ‘the right drug at the right dose the first time.’ These expectations place the prescribing physician in a dilemma and at risk of litigation, especially when evidence-based information on genotype-related dosing schedules is to all intent and purposes non-existent and guidelines, intended to improve the clinical utility of available pharmacogenetic information or tests, distance themselves from any responsibility. Lack of efficacy or an adverse drug reaction is frequently related to non-genetic factors. Phenoconversion, arising from drug interactions, poses another often neglected challenge to any potential success of personalized medicine by mimicking genetically-determined enzyme deficiency. A more realistic promotion of personalized medicine should acknowledge current limitations and emphasize that pharmacogenetic testing can only improve the likelihood of diminishing a specific toxic effect or increasing the likelihood of a beneficial effect and that application of pharmacogenetics to clinical medicine cannot adequately predict drug response in individual patients.

[starcontrol2]

Just to add something. My gp did a genetic test, he said it was available so why not and insurance fully paid.

It showed a bunch of things and shows how well you metabilize different drugs.

I was on 5 mg of lexapro and it was working fine but it showed i was a fast metabilizer of it. In theory that meant 5mg was way too little for me, yet it worked. Gp was baffled, 2 psychs were baffled since according to theory I would need 150% of the dose not 50%.

However, the difficulty in withdrawing and the awful withdrawal symptoms could maybe, possibly be aggravated by me being a fast metabolizer? That I don't know.

[compsports]

Alto has posted about this and how these tests are totally irrelevant regarding withdrawal issues.  You might want to do a search of the archives

[starcontrol2]

I have read a lot of this site even before I registered.

Here is how it "might" be relevant.

If half life of lexapro is 30 hours and one is a fast metabolizer, his/her half like could essentially be 15 hours, I don't know how much, maybe 20.

Shorter half life, heavier possibility of withdrawal. At least that's the reasoning behind prozac "bridge".

[oskcajga]

I have read a lot of this site even before I registered.

Here is how it "might" be relevant.

If half life of lexapro is 30 hours and one is a fast metabolizer, his/her half like could essentially be 15 hours, I don't know how much, maybe 20.

Shorter half life, heavier possibility of withdrawal. At least that's the reasoning behind prozac "bridge".

 

I've been told by a knowledgeable psychiatrist that the short half life of many of these antidepressants is directly related to the severity of withdrawals.  This makes intuitive sense as well - shorter half life drugs = the body has less time to reverse neuroadaptations, and the more overall shock that occurs when it's suddenly removed from our system.  That being said, there are also reports of people who suffer from long withdrawals from prozac as well - so this theory is FAR from rock-solid.  Moreover, if someone happens to suffer a severe adverse reaction to a drug like prozac, it stays in the system for like 3 months, which means that the negative reaction may have a longer time to potentate as the drug continues to circulate in the bloodstream and affect neurochemistry of the brain.  There's a lot of things to consider when thinking about half-lives and antidepressants - these are very tricky drugs.

[Altostrata]

Many give credence to the half-life theory, as well as the idea that Prozac is "self-tapering." Both are based on misinformation coming out of clinical trials.

 

Fluoxetine or Prozac is the antidepressant with the longest half-life; it is the proxy for the "half-life" theory.

 

Initially, it was claimed that Prozac did not have a withdrawal syndrome, but that was because the clinical trials were too short and subjects weren't followed long enough. It was assumed that withdrawal symptoms show up within a few days of discontinuation. With fluoxetine, because of its relatively long half-life, withdrawal symptoms show up later.

 

Therefore, as statistics on withdrawal syndrome have fewer incidents for fluoxetine than for other antidepressants, it is inferred that the deciding factor is half-life. This is questionable.

[JanCarol]

I gained a lot of respect for epigenetics here  (nods to Apace, who posted the links elsewhere, though I had just started the book when he did so!  I love synchronicity!):

 

 

As for the "predetermination" of genetics, he treats as absolute hooey.  It's all about the environment, receptors, and translation of information in proteins.  Only when a protein/amino signal fails to respond, is the gene accessed (in my humble understanding).

 

I'm not a scientist, but I like this, and he makes it understandable to a lay person.  And, his passion is evident.

[NJJ]

 

I agree with you altostrata that

 

 

"Many doctors mistakenly attribute ANY adverse effect, including withdrawal syndrome, to a lack of liver enzymes. This is yet another way they misunderstand the adverse effects of psychiatric drugs."

 

A lot of doctors are also very clueless about interactions with combination of drugs prescribed together with antidepressants, including common medications such as antibiotics, anti metics, antihestimines etc.

 

Sorry a bit off topic.....What annoys me to is our TGA has put out bulletins reporting AD withdrawal even back in the 90s but because they claim it's only 2% of the population it's only a minority of people. But Drs arnt going to report it bec they don't think it exists and not many people know what is happening to them when it occurs.

[rapunzel2]

I got 23andme test for christmas and after reading this thread here, I'm quite interested what comes up from that. 

[btdt]

I will go one step further than Alto since I took prozac first for about 2 wks had hellish sar and long long long term withdrawal from it... I do not believe in the bridge at all and would never recommend anyone bridge with prozac... not ever. 

[btdt]

I gained a lot of respect for epigenetics here  (nods to Apace, who posted the links elsewhere, though I had just started the book when he did so!  I love synchronicity!):

 

 

As for the "predetermination" of genetics, he treats as absolute hooey.  It's all about the environment, receptors, and translation of information in proteins.  Only when a protein/amino signal fails to respond, is the gene accessed (in my humble understanding).

 

I'm not a scientist, but I like this, and he makes it understandable to a lay person.  And, his passion is evident.

I watched this in good faith one hour and 8 minutes... wondering when it would get to the part about how an adverse reaction to prozac affects my genes... hmm bit of a let down nice theory it did not tell me what a cell does when it can't escape a toxin I guess it dies. 

[btdt]

https://genomind.com/genes-analyzed/

They are talking on this page about serotonin 

 

Serotonin Transporter
(SLC6A4) Protein responsible for reuptake of serotonin from the synapse Inhibition of this protein by SSRIs, 
which may lead to increased risk for non-response/side effects

Use caution with SSRIs; atypical antidepressants or SNRIs may be used if clinically indicated

 

Didn't Alto say this sort of testing was bunk?  Maybe what I am thinking of does not exist..it just seems I am having a lot...too many drug reactions. 

 

At the bottom of the page they do off this

 

Pharmacokinetic GENE PHYSIOLOGICAL ROLE IMPACT OF MUTATION TREATMENT IMPACT CYP450 
(CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5) Enzymes that metabolize medications in the liver Large number of psychiatric medications are metabolized by CYP450s

Dose adjustment (an increase or decrease) may be required

 

But the top part of the page all seems to be brain related.. maybe this is something new... hmm thanks for the heads up I will see what my doctor has to say this time it may be a no go again. 

peace

[Meimeiquest]

Ben Lynch has a lot to say about people who react to dental anesthetics. If you are into him. He uses 23andme.com testing, but you have to find a way to make sense of the results (I think you can pay at some online sites.). I just don't know if he is right or not. Yes, Genomind is mostly as you said, with the liver stuff throw in.

[Altostrata]

From The importance of MTHFR, methylation, and B vitamins

 

Chris Kresser's latest on methylation http://chriskresser.com/methylation-what-is-it-and-why-should-you-care

Believe me, even if you get a 23andme genetic analysis, it's still trial-and-error to see what works. Good luck finding someone who can interpret it.

As Chris Kresser all but admits, this is a science that's not there yet.

My understanding of the utility of MTHFR tests agrees with this article. Please note the variations in MTHFR you might see in your genetic tests are normal variations. They are extremely common. If they were dangerous, evolution would have eliminated the individuals who carry them. Since they are so very common, they probably also have some yet-to-be-discovered advantage (such as the ability to tolerate high homocysteine).

http://www.washingtonpost.com/news/wonkblog/wp/2015/09/11

Why you shouldn’t know too much about your own genes
By Carolyn Johnson September 11, 2015 Washington Post

This summer, a panel of genetics experts did something surprising: they put out a list of genetic tests people should not get.
....
There is tremendous excitement over the coming age of treatments tailored to you. And there is also this: a very long list of genes for which the best medical understanding of what they mean for our health is essentially a shrug.

The poster child for the uncertainty underlying much of the information in this brave new world is a gene called MTHFR. It
produces an important enzyme, but many medical geneticists simply sigh when they hear the gene's clumsy acronym name.

This gene has made its way on to the do-not-test list more than once, because in almost no cases do the tests have any medical utility.

Meanwhile, alternative medicine practitioners and Web sites have stepped up their claims that many people -- perhaps anyone with a family history of any disease at all -- should have the gene tested, because the information will help make them healthier.

"There’s all this excitement about genetic testing; President Obama talked about how precision medicine is going to empower all of us. So here you have these practitioners saying, 'Let me empower you,'" said Timothy Caulfield, a professor of health law and science policy at the University of Alberta. "It’s this fascinating shift from science to bunk, and the shift is made very, very quickly, and often without any real sort of regulatory oversight."

Here is the under-appreciated corollary to the new age of personalized medicine: just because you can do a genetic test, doesn’t mean you should.

There's a natural human impulse to search for explanations for health problems, and the genome provides a powerful way to deepen that search. But in addition to the genuine promise that the genome brings, it also creates a niche where science can be exploited and vulnerable people seeking answers misled.

“It’s a ripe area for people to claim a scientific basis for stuff that may actually not be true at all, or may have a kernel of truth,” said Robert C. Green, a medical geneticist at Brigham and Women’s Hospital and Harvard Medical School. “We in genomics and society face a choice. Are genomes going to be so democratized and unregulated that we create an entirely fraudulent industry around them?”

Here is what people agree on: MTHFR is a gene that creates an enzyme involved in processing the vitamin folate and inn recycling a blood chemical called homocysteine. The products of the MTHFR reaction are involved in lots of important bodily processes, such as DNA synthesis.

There are naturally-occurring variations in the gene that mean it functions less well in some people, sometimes causing high homocysteine levels. In early studies, those high levels were correlated with cardiovascular disease. That generated intense interest in the gene and studies of the common variants of the gene. But the balance of evidence has swung back to deem those tests of "minimal clinical utility," according to the American College of Genetics and Genomics.

Where the disagreement begins is whether those naturally occurring variations -- which are common, carried by as many as 40 percent of individuals in some ethnic groups -- have a health effect.

For MTHFR, “there was this heyday of testing when we had all this preliminary data,” said Elizabeth Varga, a genetic counselor at Nationwide Children’s Hospital in Ohio. Then larger, better designed studies began to show that the initial associations didn’t hold up.

“So really, the medical community has done an about-face, and that confuses people," Varga said.

....the MTHFR saga highlights something a little more nuanced than a person wrestling with the possibility that they are at elevated risk for Alzheimer’s disease. There are more than 3,000 published papers examining this one gene, often of varying quality, and in connection with a slew of frightening diseases. Critics of the test worry that someone without medical training may not understand how to evaluate the nuanced and often contradictory evidence.
....
Amanda Webb's quest to understand her 11-year-old daughter’s unidentified sickness has been less straightforward. Webb, 37, of Upper Arlington, Ohio, was alarmed when she found out her daughter carried two variants of MTHFR and wondered if it was the key to understanding her daughter's frequent infections with walking pneumonia. She soon found herself surrounded by contradictions. Web sites had all sorts of information about the gene, but Webb was skeptical of much of it and found she had to be very picky about what she believed. She called Varga and learned, to her disappointment, that the test didn't point to any treatment. When she went to holistic doctors, they told her to change her daughter’s diet and take more supplements.
....
Half a dozen medical specialists contacted for this story said MTHFR testing doesn't reveal actionable information and that while there may be occasional rare exceptions, it should not be done.
....
But the test is still ordered by many physicians and sought out by patients. And there are many online forums and Web sites that say the information is useful. One source that many patients with questions stumble on is run by Ben Lynch, a naturopathic practitioner from Seattle. Lynch owns a company that sells supplements. He also runs MTHFR.net, a Web site that provides information about the gene and provides health recommendations -- many of which are uncontroversial, such as eating more leafy vegetables and exercise. But he also recommends vitamin supplements, and acknowledged this was a conflict of interest in an interview.

Asked about the absence of large, randomized trials to back up his recommendations, Lynch described his research as drawing heavily on published scientific papers and his own knowledge of biochemistry.

“I’m saying we can’t wait for research to prove what I’m doing,” Lynch said.
....
Asked whether there are other partially-understood genes where a confusing situation could arise, Khoury had a glib answer.
"Let put it simply,” Khoury said. “99 percent or more of the genome falls there.”

Note: I am heterozygous for the “thermolabile” variant c.665C T and c.1286A. I have high homocysteine. I am not the least bit worried about this.

Genetics in Medicine (2013) 15, 153–156 doi:10.1038/gim.2012.165
ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing
Scott E. Hickey MD, FACMG, Cynthia J. Curry MD, FACMG & Helga V. Toriello PhD, FACMG
Published online 03 January 2013

Abstract and free full text at http://www.nature.com/gim/journal/v15/n2/full/gim2012165a.html

MTHFR polymorphism testing is frequently ordered by physicians as part of the clinical evaluation for thrombophilia. It was previously hypothesized that reduced enzyme activity of MTHFR led to mild hyperhomocysteinemia which led to an increased risk for venous thromboembolism, coronary heart disease, and recurrent pregnancy loss. Recent meta-analyses have disproven an association between hyperhomocysteinemia and risk for coronary heart disease and between MTHFR polymorphism status and risk for venous thromboembolism.

There is growing evidence that MTHFR polymorphism testing has minimal clinical utility and, therefore should not be ordered as a part of a routine evaluation for thrombophilia.

The 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the primary circulatory form of folate, and a cosubstrate for homocysteine remethylation to methionine. Methionine is subsequently converted to S-adenosylmethionine, which serves as an essential methyl donor in reactions involving nucleic acids, proteins, and many other biological compounds. There are two commonly recognized polymorphic variants in the gene encoding for this enzyme: the “thermolabile” variant c.665CT (p.Ala222Val), historically more commonly referred to as C677T, and the c.1286AC (p.Glu429Ala) variant; both are missense changes that are known to decrease enzyme activity.^1,2 It is estimated that >25% of Hispanics and between 10 and 15% of North American Caucasians are homozygous for the “thermolabile” variant.³ Variants c.665CT and c.1286AC are in linkage disequilibrium with each another, and therefore a combination of both variants is usually seen only in individuals who are compound heterozygotes in trans.⁴ Homozygosity for one variant in combination with heterozygosity for the other variant is rare.⁵ Targeted mutation analysis for the c.665CT and c.1286AC variants is available in more than 50 Clinical Laboratory Improvement Amendments–certified laboratories in the United States.

Reduced enzyme activity of MTHFR is a genetic risk factor for hyperhomocysteinemia, especially in the presence of low serum folate levels.6,7,8 Mild to moderate hyperhomocysteinemia has been identified as a risk factor for venous thrombosis9,10 and has been associated with other cardiovascular diseases, such as coronary artery disease.11,12,13 Hyperhomocysteinemia is multifactorial, involving a combination of genetic, physiologic, and environmental factors.3,14 Several enzymes with vitamin B cofactors—including vitamin B6, vitamin B12, and folate—are involved in regulating homocysteine levels. Individuals who are MTHFR polymorphism homozygotes may have hyperhomocysteinemia, usually to a mild or moderate degree of uncertain clinical significance. As mentioned, homocysteine is associated with coronary artery disease, although this appears to be independent of MTHFR genotype status. 15 Although B vitamin supplementation has been shown to decrease plasma homocysteine levels, the effect on cardiovascular end points has been mostly negative.16,17,18 Some authors have found mild significant effects on stroke;16,18 however, a meta-analysis of homocysteine-lowering trials did not find evidence that supplementation with B vitamins, including folic acid, resulted in any decrease in cardiovascular events or mortality.19 Furthermore, a more recent meta-analysis of unpublished data sets has cast doubts on the hypothesis that lifelong moderate homocysteine elevation has any effect on cardiovascular disease, raising the possibility that publication bias accounted for the previously observed aggregate association.20

The potential associations between MTHFR genotype status and a number of medical complications have been evaluated using methodologies such as case–control, cohort, Mendelian randomization, and meta-analysis. A modest positive association has been found between the MTHFR “thermolabile” polymorphism and many different medical complications, including, but not limited to, thromboembolic disease (in non-North-American populations only), 21,22 stroke,23,24,25,26,27 aneurysm,28 peripheral artery disease,29 migraine,30 hypertension,31,32 recurrent pregnancy loss,33,34 male infertility,35,36 risk for offspring with neural tube defects,37,38 certain cancers,39,40,41 neuropsychiatric disease,42 and chemotherapy toxicity.43,44 Conversely, many other studies looking at similar complications found no statistical association.45,46,47,48,49,50,51,52 The c.1286A C variant has been studied less, but current evidence suggests that it is milder than the “thermolabile” variant.53,54,55,56 Preliminary findings in combined genotypes have found that they are not significantly different from controls.57,58

Because MTHFR polymorphism is only one of many factors contributing to the overall clinical picture, the utility of this testing is currently ambiguous. Furthermore, US-mandated fortification of grain products with folic acid to decrease the incidence of neural tube defects has resulted in increased serum folate concentrations and lowered serum total homocysteine levels in the general population.59 This public health initiative may be incidentally reducing some of the perceived risk associated with MTHFR polymorphisms. 60,61 This is hypothesized to be one reason that an association between the “thermolabile” variant and venous thromboembolism is no longer observed in the North-American population.21

The American Congress of Obstetricians and Gynecologists does not recommend the measurement of homocysteine or MTHFR polymorphisms in the evaluation of the etiology of venous thromboembolism. 62 The British Committee for Standards in Haematology and the British Society for Haematology do not include MTHFR polymorphism testing as part of their clinical guidelines for heritable thrombophilia testing. 63 The ACMG consensus statement on factor V Leiden testing briefly references the limited clinical utility of MTHFR polymorphism testing and that homocysteine measurement may be more informative. 64

A medical geneticist may be asked to evaluate a patient who has tested positive, either heterozygous or homozygous, for an MTHFR polymorphism (Box 1). The geneticist should assess the information given to the family by the previous provider, including the interpretation pertaining to causality for presenting symptoms. It is imperative that the geneticist ensure that patients have received thorough and appropriate evaluations for their symptoms because it is not uncommon that medical problems are incorrectly attributed to positive MTHFR status. Often, referral to a hematologist or maternal–fetal medicine specialist for further evaluation of their symptoms is indicated.

Once a patient has been found to carry one or more MTHFR polymorphisms, genetic counseling is very difficult, given the vast medical literature exploring possible associations with a wide variety of diseases. In general, the following genotypes currently appear unlikely to be of clinical significance: “thermolabile” variant c.665C T heterozygote, c.1286A  C homozygote, or (c.665C  T); (c.1286A  C) compound heterozygote. There is theoretical reason to be concerned that the rare individuals with triple variant MTHFR genotypes (i.e., individuals who are homozygous for one variant and heterozygous for the other) may have resulting clinical risks, although that is currently speculative.

A fasting total plasma homocysteine level may be obtained in any patient who is homozygous for the “thermolabile” variant, in order to provide more information for counseling. For the purpose of laboratory interpretation, it should be noted that total homocysteine levels increase with age and are lower in the pregnant population.65,66 Genetic counseling should take into account the clinical reason for which the test was performed. Many studies have revealed discrepant findings between Caucasians and Asians.21,35,51 It seems most likely that this is related to dietary factors, such as folic acid intake; however; caution should be applied when generalizing the following recommendations to the Asian-American population.
....
....Patients should be counseled that it is important to provide their MTHFR genotype status to any physician who is considering starting them on types of chemotherapy whose activity depends on intracellular concentration of folate (e.g., methotrexate). In individuals who have a known thrombophilia, such as factor V Leiden or prothrombin c.*97G  A, most available studies support the contention that MTHFR genotype status does not alter their thrombotic risk to a clinically significant degree. 72

An at-risk individual may elect to take a daily vitamin B supplement, such as a multivitamin or prenatal vitamin, although there is currently no evidence that specific treatments reduce risks associated with hyperhomocysteinemia or MTHFR genotype status. Because folic acid and vitamin B12 toxicities are rare, the risks associated with daily supplementation are low. An individual who elects to take supplemental pyridoxine, however, should be aware of the risk for ataxia and sensory neuropathy. 70

The upshot of the articles above is that MTHFR status is generally irrelevant, except for very, very rare homozygous combinations, which are still under investigation.

Inadequate B vitamins, particularly B12, are quite common in the modern diet. As we get older, our ability to make B12 diminishes.

It may very well be that supplementation of vitamin B12, or other B vitamins, makes you feel better. (Many people with withdrawal syndrome cannot take B vitamins at all because they find them too stimulating.) Whether this "treats" a MTHFR variation (which, after all, is NORMAL and does not indicate a disease state) is unknown.

The value of measuring homocysteine is limited, as apparently only very high homocysteine is medically meaningful.

Cyanocobalamin will release a very tiny amount of cyanide as it is metabolized. There is very little risk from it. If it's the only kind you can get, I would not worry about it.

PS If you're getting good results from cyanocobalamin, you don't require methylcobalamin. Your methylation of cyanocobalamin is working fine.

It's absolutely essential that anyone concerned about their MTHFR polymorphism read this interview with naturopath Ben Lynch, one of the foremost experts on MTHFR, on naturopath Chris Kresser's site. My highlights below:

What Influences Methylation? An Interview with Dr. Ben Lynch
December 10, 2015 by Chris Kresser

 

Chris Kresser: .... One of the things I like to say is the mutation of a gene doesn’t necessarily guarantee dysregulation of that gene. In other words, mutation doesn’t mean that you absolutely will have a dysfunctional gene. It means it’s more likely to dysfunction....

Dr. Ben Lynch: Well, just to keep it very simple and overreaching and broad .... we’ll just say that you find that you do have a genetic mutation, like MTHFR, and you’re like, “Oh, crap,” but the reality is it may or may not be causing a problem.

....

Dr. Ben Lynch: So I look at genetic polymorphisms as a degree of how much you overburden the system, and the more work that you create for that said gene, then you have to support it more. And a genetic polymorphism may affect it or it may not.

Chris Kresser: Right, so we’re talking about predispositions here, it sounds like—more a question of, you know, someone who has a polymorphism in a particular gene may be predisposed to that gene functioning less optimally, especially when you add a number of environmental challenges that we’re facing today, like poor diet, heavy metal toxicity, dysbiosis, disrupted gut microbiome, air pollution both indoor and outdoor, nutrient imbalances, a relative excess of copper and deficiency of zinc, etc., etc., etc.—in a nutshell, the modern lifestyle, right?

Dr. Ben Lynch: Yeah. Let’s pick a simple gene to go with. We’ll talk about MTHFR because it’s the golden child on the block for some reason.

....

Dr. Ben Lynch: Say, you identify that you have this MTHFR gene problem, and you go to the internet and you read about, and you’re like, “Oh, crap. I have this.” I have it. I went, “Oh, crap,” when I read about it. I have one copy of 677 and one copy of 1298, personally, and so do a couple of my kids, and I was really concerned about it, and then I started learning that, well, you can actually get the same nutrient that the MTHFR enzyme produces itself by eating leafy greens.

Chris Kresser: Right.

Dr. Ben Lynch: So if you’re eating a bunch of leafy greens, then that MTHFR enzyme isn’t really doing too much of a problem for you, and if you’re not drinking that much alcohol, then you don’t really have that much of a burden either, along with other things.

In short, eat leafy greens.

I hope these statements by Ben Lynch (which, by the way, arise from a conversation I had with him on his Web site years ago) are the beginning of the end of the MTHFR "treatment" fad.

 

http://health.clevelandclinic.org/2013/09/a-genetic-test-you-dont-need/

A Genetic Test You Don’t Need
Testing MTHFR is usually unnecessary
September 27, 2013 / By Charis Eng, MD, PhD
Founding Chairwoman of the Genomic Medicine Institute
 

As a geneticist and researcher, I believe in the power of genetic testing. By identifying genetic mutations, we can improve care and save lives.
But just because we can test something doesn’t always mean we should.
Take the MTHFR gene, for example. MTHFR codes for an enzyme that helps your body convert homocysteine into an amino acid that processes proteins. People with mutations or variations of MTHFR may end up with homocystinuria, a disorder that affects the eyes, joints and other parts of the body. High homocysteine levels also have been connected to heart disease and strokes.

There is a genetic test for MTHFR variations. But there’s also a cheaper and more accurate way to test for whether MTHFR variations are causing disease. We simply check the levels of homocysteine in the blood. If levels are high, we can react appropriately. If homocysteine levels are normal — even if there is an MTHFR variation — then nothing needs to be done clinically.
In other words, the homocysteine levels determine our actions, not the MTHFR test results.
....
Not only is the test for homocysteine levels simple, but so are the solutions. People with high homocysteine levels typically respond well to supplementation with vitamins such as B6, B12, and folate or folic acid.

The same is true of other disorders that might be related to MTHFR. For example, mutations in MTHFR have been associated with some neural tube defects in babies. But rather than having an unnecessary test for MTHFR gene variations, pregnant women should simply take prenatal vitamins that contain higher folate.

Folate effectively bypasses the problem — and it’s benign at the doses that come in vitamins.
....

 

Here is a common-sense way to improve methylation without relying on expensive genetic tests and interpretations thereof.

http://www.huffingtonpost.com/dr-mark-hyman/nutrition-tips-folic-acid_b_601126.html

Nutrition Tips: Folic Acid: Killer or Cure-All?
Mark Hyman, MD Updated: 11/17/2011
 

....We are all biochemically individual and genetically unique, and about 35 percent of us have a genetic variation in a gene called MTHFR that helps neutralize the folic acid. If this doesn't work well, then more of the folic acid accumulates from the fortified food and supplements we consume. Those who have this gene are at increased risk of colon cancer because they produce more pre-cancerous colon polyps. In fact, high dose folate supplementation in these people reduced their risk of polyps. (iv)

The good news is that you can take the nature-made form of this nutrient -- called methyl folate (and there are a few forms of that too). This is what should be in food and vitamin supplements. Many conscientious companies are now using only this form of the nutrient, but it is more expensive.

Here's what you should do:

Don't eat fortified foods! If it needs to be fortified with folic acid, that is because it has been impoverished and refined in the first place (think white flour, white rice, cereals and processed foods). Just eat real, whole fresh food!

Look at your supplement label! If it says "folic acid" then find another vitamin that has the words "L 5 methyl-tetrahydrofolate" or "5 formyl tetrahydrofolate" on the label.

Now for those who want know a little bit more about the reason why folate and its companions B6 and B12 are the most critical and health promoting hit parades in the nutrient world.
....
Methylation is a key biochemical process that is essential for the proper function of almost all of your body's systems. It occurs billions of times every second; it helps repair your DNA on a daily basis; it controls which genes are turned on or turned off; it controls homocysteine (an unhealthy compound that can damage blood vessels); it helps recycle molecules needed for detoxification; and it helps maintain mood and keep inflammation in check.

To keep methylation running smoothly you need optimal levels of B vitamins. Without enough B vitamins methylation breaks down, and the results can be catastrophic. In these cases we see more birth defects like spina bifida (as with the Chinese babies), more cases of Down's syndrome, and more miscarriage.
A breakdown in methylation also puts you at higher risk for conditions like osteoporosis, diabetes, cervical dysplasia and cancer, colon cancer, lung cancer, depression, pediatric cognitive dysfunction (mood and other behavioral disorders), dementia, and stroke. And like Mr. Roberts and Mr. McNally, you may be at higher risk for cardiovascular disease.

To avoid all of these problems, the key is to optimize methylation. That means avoiding the things that cause your methylation to break down, testing to find out how well your methylation is working and including the things that support proper methylation. Let's look at how to do that.

8 Factors that Affect Your Methylation Process

Eight major factors negatively impact methylation. They are:

1. Genetics. Like an estimated 20-30 percent of us, you could be genetically predisposed to high homocysteine.

2. Poor diet. The word "folate" comes from "foliage." You need to eat plenty of leafy greens, beans, fruit, and whole grains to get adequate levels of vitamins B6 and B12, betaine and folate (all in the right nature made forms). Egg yolks, meat, liver and oily fish are the main dietary sources of vitamin B12 -- so long-term vegan diets can be a problem. Plus, certain compounds can raise levels of homocysteine and deplete the B vitamins. These include excess animal protein, sugar, saturated fat, coffee and alcohol. Irradiation of food depletes nutrients, so foods treated this way may be lower in B vitamins, too.

3. Smoking. The carbon monoxide from cigarette smoke inactivates vitamin B6.

4. Malabsorption. Conditions like digestive diseases, food allergies, and even aging can reduce absorption of nutrients.

5. Decreased stomach acid. Aging and other conditions can reduce stomach acid -- and therefore absorption of vitamin B12.

6. Medications. Drugs like acid blockers, methotrexate (for cancer and arthritis and other autoimmune diseases), oral contraceptives, HCTZ or hydrochlorthiazide (for high blood pressure) and Dilantin (for seizures) can all affect levels of B vitamins.

7. Other conditions. These include hypothyroidism, kidney failure or having only one kidney, cancer and pregnancy.

8. Toxic exposures. Some toxins such as mercury can interfere with vitamin production.

Watch out for these factors and you will go a long way toward protecting your methylation.

Measuring Your Own Methylation Process

To find out if your methylation process is optimal, ask your doctor for the following tests:

1. Complete blood count. ....large red blood cells or anemia can be a sign of poor methylation. Red blood cells with a mean corpuscular volume (MCV) greater than 95 can signal a methylation problem.

2. Homocysteine. This is one of the most important tests you can ask for. The normal level is less than 13, but the ideal level is likely between six and eight.

3. Serum or urinary methylmalonic acid. This is a more specific test for vitamin B12 insufficiency. Your levels may be elevated even if you have a normal serum vitamin B12 or homocysteine level.

4. Specific urinary amino and organic acids. These can be used to look for unusual metabolism disorders involving vitamins B6 or B12 or folate, which may not show up just by checking methylmalonic acid or homocysteine.

12 Tips to Optimize Your Methylation Process

Just as there are many causes of poor methylation, there are lots of things that support its proper functioning. Here's how to optimize methylation and prevent conditions like heart disease, cancer, dementia, depression and more.

1. Eat more dark, leafy greens. You want to eat l cup a day of vegetables like bok choy, escarole, Swiss chard, kale, watercress, spinach, dandelion, mustard, collard or beet greens. These are among the most abundant sources of the nutrients needed for optimal methylation. You can't get too much folate from food.

2. Get more Bs in your diet. Good food sources include sunflower seeds and wheat germ (vitamin B6), fish and eggs (vitamin B6 and B12), cheese (B12), beans and walnuts (vitamin B6 and folate), leafy dark green vegetables, asparagus, almonds, whole grains (folate) and liver (all three).

3. Minimize animal protein, sugar and saturated fat. Animal protein directly increases homocysteine. Sugar and saturated fat deplete your body's vitamin stores.

4. Avoid processed or refined foods and canned foods. These are depleted in vitamins.

5. Avoid caffeine. Excess amounts can deplete your B vitamin levels.

6. Limit alcohol to three drinks a week. More than this can deplete your B vitamin levels.

7. Don't smoke. As noted above, smoking inactivates vitamin B6.

8. Avoid medications that interfere with methylation. See notes on this above.

9. Keep the bacteria in your gut healthy. Take probiotic supplements and use other measures to make sure the bacteria in your gut are healthy so you can properly absorb the vitamins you do get.

10. Improve stomach acid. Use herbal digestives (bitters) or taking supplemental HCl.

11. Take supplements that prevent damage from homocysteine. Antioxidants protect you from homocysteine damage. Also make sure you support methylation with supplements like magnesium and zinc.

12. Supplement to help support proper homocysteine metabolism. Talk to your doctor to determine the best doses and forms for you. Here are a few suggestions:

• Folates Amounts can vary based on individual needs from 200 mcg to one mg. Some people may also need to take preformed folate (folinic acid or five formylTHF, or five methyl folates) to bypass some of the steps in activating folic acid.

• Vitamin B6: Take two to five mg a day. Some people may need up to 250 mg or even special "active" B6 (pyridoxyl-5-phosphate) to achieve the greatest effect. Doses higher than 500 mg may cause nerve injury.

• Vitamin B12: Doses of 500 mcg may be needed to protect against heart disease. Oral vitamin B12 isn't well absorbed; you may need up to 1 or 2 mg daily. Ask your doctor about B12 shots or doses you can take under the tongue.

• Betaine: This amino acid derivative is needed in doses from 500 to 3,000 mg a day, depending on the person.

Please note that B vitamin supplementation may be too activating for people whose nervous systems have been sensitized by withdrawal. Until your nervous system settles down, eat more fresh leafy green vegetables, nuts, and seeds. This will help you get the B vitamins you need.

 

[btdt]

Thanks Alto.  

[btdt]

https://genomind.com/genes-analyzed/

They are talking on this page about serotonin 

 

Serotonin Transporter

(SLC6A4) Protein responsible for reuptake of serotonin from the synapse Inhibition of this protein by SSRIs, 

which may lead to increased risk for non-response/side effects

Use caution with SSRIs; atypical antidepressants or SNRIs may be used if clinically indicated

 

Didn't Alto say this sort of testing was bunk?  Maybe what I am thinking of does not exist..it just seems I am having a lot...too many drug reactions. 

 

At the bottom of the page they do off this

 

Pharmacokinetic GENE PHYSIOLOGICAL ROLE IMPACT OF MUTATION TREATMENT IMPACT CYP450 

(CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5) Enzymes that metabolize medications in the liver Large number of psychiatric medications are metabolized by CYP450s

Dose adjustment (an increase or decrease) may be required

 

But the top part of the page all seems to be brain related.. maybe this is something new... hmm thanks for the heads up I will see what my doctor has to say this time it may be a no go again. 

peace

 

While I do believe Alto in there is not much relationship between genetics and wd.. eat your greens is the cheap way around the mather issue... this came to my attention today kind of related kind of not... 

 

" One pharmacogenetic study has been conducted to assess the relationship between functional variation in the serotonin transporter gene (SLC6A4) and changes in IELT after SSRI treatment [38]. These genetic relationships with increased IELTs for the treatment of LPE may be informative for identifying underlying genetic contributors for anorgasmia or delayed orgasm in males being treated with SSRIs for mood or anxiety disorders."

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

 

I wish they would study female sexual problems post ssri use. 

[downtongirl]

Ok....got some interesting results back from some genetic testing....I already knew from a couple of months ago that I tested positive for the homozygous CY677T and now I have found out through testing that I have some other gene mutations that might affect my metabolism/withdrawal of antidepressants.  Enzymes I have a polymorphism to are....CYP1A1, CYP1B1, CYP2C19 (this one has a lot to do with antidepressants), I am also absent with the COMT Enzyme, I am considered to have a slow metabolizer metabolism polymorphism to NAT@ enzyme, SOD2 enzyme.  Does anyone else have these mutations and if so do you take supplements for them?  It has been suggested to me that I add NAC, L Methylfolate, Vitamins B6, B12.

[btdt]

Ok....got some interesting results back from some genetic testing....I already knew from a couple of months ago that I tested positive for the homozygous CY677T and now I have found out through testing that I have some other gene mutations that might affect my metabolism/withdrawal of antidepressants.  Enzymes I have a polymorphism to are....CYP1A1, CYP1B1, CYP2C19 (this one has a lot to do with antidepressants), I am also absent with the COMT Enzyme, I am considered to have a slow metabolizer metabolism polymorphism to NAT@ enzyme, SOD2 enzyme.  Does anyone else have these mutations and if so do you take supplements for them?  It has been suggested to me that I add NAC, L Methylfolate, Vitamins B6, B12.

 

maybe ask here

 

contact@mthfrsupport.com

[btdt]

GeneSight Psychotropic Report Classifies Medications Based on Gene Interactions

GeneSight Psychotropic now analyzes more than 18,247,680 permutations of an individual’s gene-drug interactions, including four newly added genes, UGT1A4, UGT2B15, HLA-B*1502, and HLA-A*3101, in addition to the genes already included, CYP2D6, CYP2C19, CYP2C9, CYP1A2, CYP2B6, CYP3A4, SLC6A4, and HTR2A.

 

These are the one thought important by this company.

 

GeneSight Psychotropic is one of four pharmacogenomic tests available from Assurex Health, including GeneSight ADHD, GeneSight Analgesic, and GeneSight MTHFR.

 

About Assurex Health

Assurex Health is a commercial-stage, informatics-based precision medicine company providing treatment decision support to healthcare providers for behavioral health and chronic pain conditions. We help people achieve mental wellness with advanced CPGx™, a proprietary combinatorial pharmacogenomics technology providing individualized treatment support for neuropsychiatric conditions.

Assurex Health is the leader in neuropsychiatric combinatorial pharmacogenomics. It was founded in 2006 with licensed, patented technology from Mayo Clinic and Cincinnati Children’s Hospital Medical Center, who continue to be research collaborators. Assurex Health is the only company in the category with multiple peer-reviewed, published studies that demonstrate the clinical validity and clinical utility of its technology, including its substantial healthcare cost savings benefit. The company has grown every quarter, and also has begun to expand internationally through a partnership with Canada’s Centre for Addiction and Mental Health (CAMH).

https://assurexhealth.com/pr-new-genesight/

 

on further looking 

http://mysonhas2brains.blogspot.ca/2014/02/genesight-testing-for-medication.html

My psychiatrist ordered this test for me to determine which antidepressant to use. I was skeptical that DNA could actually do this. My skepticism was confirmed when my doctor handed me a copy of the results of my test. I read through the entire 4 page report. On page 3 in fine print there was a disclaimer that says "The information in this report is provided as a service AND DOES NOT CONSTITUTE MEDICAL ADVICE"! That's right, the company that performs the test admits that the information contained in their test is NOT MEDICAL ADVICE! The purpose of the test is to tell doctors which drugs will work the best. How can Assurex Health sell this test and then claim that they are not giving medical advice? This is a fraudulent test performed by a fraudulent company. I've reported this to my state's medical board as I believe this constitutes insurance fraud

who knows may be its best use is an excuse to never have to try any psych drugs 

[btdt]

Assurex Health Passes Quarter Million Patients Tested with GeneSight

It is bringing in the money... if nothing else.

http://www.prnewswire.com/news-releases/assurex-health-passes-quarter-million-patients-tested-with-genesight-300214569.html

 

GeneSight is the only neuropsychiatric pharmacogenomic test explicitly covered by Medicare and is also available through the U.S. Department of Veterans Affairs.

 

 

https://www.sciencedaily.com/releases/2016/06/160621091040.htm

"The medical community continues to recognize that genetic variation may contribute to disparate patient reactions to drugs," Dr. Frye says. "For example, some may experience adverse side effects, while others respond positively to the same drug." He says the different responses to pharmacotherapy provide a unique opportunity to develop pharmacogenetic guidelines for psychiatry.

[btdt]

Given my new state of being I am searching for a genetic tool that would help me know which surgical meds would be the least problematic.. I would like to know about all drugs to secure a more peaceful future for myself... I just can't seem to find this sort of test perhaps it does not exist. 

 

I don't really care about any psych drug test cause I am NEVER taking another psych drug as long as I live.

 

Whatever the cause I can no longer safely go to the dentist... lidocaine and epi reactions... there has to be an answer mostly I get dentists who think or outright say it is impossible... or get nothing... what the he... am I that much of an anomaly.  Is it all in my head... no .. I could not walk straight for 3 months after a lidocaine reaction... why I react now and never before can't be ascertained.  Is it some post wd thing... would anything show on any of these tests if it is?  

 

Those are my questions I can't find answers to. 

 

if you have any answers or ideas please post them... 

 

wishing you all peace

 

(big answer year post AD was I must have had a coincidental TIA at the precise time I had the lidocaine injection - unrelated)  I am still never having it again.

[compsports]

bdtd,

 

If I remember correctly, Alto wrote a post about the limitations of this type of testing that you might want to search for.

 

Regarding dentists who say the lidocaine and epi reactions are not possible, I would find another dentist.   There are other drugs they can use.

 

Concerning surgical meds, the only drug that gave me a problem after my 2015 septoplasty was an antibiotic given pre operatively that I should have never agreed to.   My surgeon had asked me if I wanted it and I stupidly said yes.

 

But other than that, everything was fine.   I had told the anesthesia resident that I was worried that due to having cognitive issues, I was worried about med side effects.   So she said everything would be minimized and it definitely was.

 

I guess what I am saying is if you are worried about side effects of surgical meds, meet with someone ahead of time so you can make sure they are minimized.

 

Oh and skip the versed that is routinely given for anxiety as a preop measure which is what I did.

 

CS

[rapunzel2]

I have heard people mention a gene test, which shows how fast somebody metabolizes drugs. I tried to find information from the forum with search, but didn't manage. If somebody knows what kind of gene test it is, I'm interested.

 

Also, I know some people have done MTHFR test. What results did you have and how did it impact you later - what actions did you take, did your health improve, etc?

 

My nutritionist mentioned also two other tests:

- APOe - related to Alzheimers https://ghr.nlm.nih.gov/gene/APOE

- ATP7B - related to Wilson's disease https://ghr.nlm.nih.gov/gene/ATP7B. It's related to copper transportation

 

Does anybody know anything about those tests, has anybody done them?

 

Any other genetic tests, that could be helpful? 

[Flowers]

I am thinking of getting the liver enzyme test done to show if I can or can't metabolise Citalopram. I expect it will show up OK and that my symptoms are from WD. Whilst researching this I came across another test  (bloods and urine) offered by the clinic which is looking into nutrition and cerebral function.

 

This involves testing urine which shows the analysis of urinary catabolites of the three principal neurotransmitters and is a peripheral indicator of it's activity. Dopamine, Serotonin and Noradrenaline.

 

Also evaluated are fatty acids Omega 3 and 6.

 

They look at vitamins and minerals such as Ferritin, Folic Acid, B12, Zinc and Selenium and finally Homocysteine B6 B9 and B12.

 

If anyone has undertaken these tests I would be very interested to hear from you?  Or any comments/views appreciated too.

 

Flowers xxx

 

[Hope]

I am just curious.  I recently was tested by my ARNP which showed that I have a genetic anomaly which can cause my brain to not know where to take serotonin.  Hence, I can have all the serotonin my brain needs, but it can't get to the places it needs to get at times.  It's been shown to connect with depression, anxiety, and alcoholism.  I'm just wondering if anyone has heard of the link between this particular genetic variant and SSRI withdrawal and reinstatement success? 

 

-on Paxil for 13 years, with one unsuccessful withdrawal attempt and reinstatement which cleared me completely in an few months

-cross-tapered to zolodt successfully-VERY SLOWLY

-currently crosstapering from zoloft to Viibryd and not doing well at all, considering reinstatement or Zoloft but afraid 

[broadmargin]

I just had the Genesight test done and i got the results yesterday.  It's interesting.

I have the S/S allele for the SLC6A4 gene.  So this means that my serotonin transporters are not so great.  It also means that standard SSRIs don't work well for me (according to the test).

 

It mentioned that i should not take Paxil because i would have more side effects than normal.  This ended up being true.  I had the worst side effects with Paxil. 

It also said that Lexapro would require a smaller dosage to get normal results.  This was also true.  I took 5mg and got results.  10mg was a bit much, and 15mg was way too much.

 

So, the suggestion is Viibryd, but i'm not trying to jump to a new AD.  I'm just trying to get stable so i can start tapering down the road.  I know i can't taper right now.  It's gonna take time for me to get in a good place, and then i can slowly start moving down.

 

Anywho.  The thinking is that the S/S or S/L allele on the SLC6A4 gene implies less tolerance for stress for the individual because of the poor SERT.

[broadmargin]

I should note that my tolerance for stress is very low, and has been all my life.  I have never been diagnosed with MDD, but i have been diagnosed GAD my whole life.  I get stressed out about almost everything there is to stress out about.  So i've been on various drugs to reign in the stress response.

 

I'm now focusing on therapy and meditation to obtain skills for lowering my overall stress levels (which are generally always quite high).  It's an interesting thing knowing that most of your problems root from anxiety and stress.  It's even more interesting to see data that may imply that it is a genetic thing (which could still be overcome with proper stress management)

[MNgal1960]

Hi. I'm curious about who has had genetic resting to determine of they are fast (or slow metabolizers) metabolizers of their med? And has it affected their dosing?

 

In my case. I had the testing done and I got the result that I am a hyper-fast metabolizer of Valium. I dose my V 3 times/day. I thought I needed to do so because of the test results.

 

My new doctor doesn't seem to believe these genetic test results mean anything. He thinks I could dose 2 times/day. Because of the nuisance of carrying the bottle of liquid with me and trying to find a place to discretely drink it in the afternoon, I want to go to twice daily dosing.

 

I wonder if anyone on here has any knowledge or experience with genetic testing and whether it has influenced their dosing schedule.

 

Thanks.

 

MN

[Altostrata]

MNgal, I would not use any genetic test as a guide to dosing. There are many factors in drug reactions. The frequency of your Valium dosing depends on your symptom pattern. Please discuss in the benzo forum.