From Dr. Trescott’s lecture given to the Physician Partners of America: “Your Genes, Your Pain Drugs and You Or “Why Every Pain Physician Should be Testing Your Genes“
When the patient says, “This doesn’t work,” or, “I’ve been too sensitive,” or, “My mother had a terrible time with medicine X and I’ve had a terrible time with medicine X”, that should really tell you there’s likely to be a genetic problem there. Trescott
Dr. Trescott is past President of the American Society of Interventional Pain Physicians. (Image from the Pain and Headache Center website).
We know that many people with fibromyalgia and chronic fatigue syndrome respond very differently to drugs. A drug that works great for one person might have no effect in another person or even make another ill.
Why such variability? I’ve long assumed this meant that many people diagnosed with ME/CFS and FM actually have a different illness, but a recent lecture presented by the Physician Partners of America suggested that’s not necessarily true. It’s possible that underlying genetics or epigenetic changes which affect how our metabolism breaks down substances could play a role.
The Genes
How you respond to a drug partly comes down to your genes. The human race is very variable genetically. A lot of that variability lies in small genetic variations called gene polymorphisms which can alter how effectively that gene works. These polymorphisms can have no effect or cause the gene to work less or more effectively.
Most people are normal – they have two “good” copies of a gene which allows them to metabolize substances properly. A significant number of people, however, have “good” and “bad” copies of a gene which can inhibit their ability to break down drugs. A smaller number of people (poor metabolizers) have two bad copies of a gene – they hardly break down some drugs at all.
Others with multiple copies of good genes (ultra-metabolizers) can find that even normal amounts of a drug can make them sick as they metabolize the drug into substances that cause harm. Rapid metabolizers of oxycodone, for instance, will produce high levels of oxymorphone, which causes nausea, sedation and other symptoms.
The pain field is a perfect place to look for genetic anomalies in drug metabolism because responses to pain drugs are all over the map. In fact, the process of producing a pain sensation is so complex that some despair of ever producing really effective pain drugs. Part of that complexity lies in the genes that produce the enzymes that break down pain drugs.
The lecturer, Andrea Trescott, MD, a well known pain researcher and doctor, provided a dramatic personal example of the effects a gene polymorphism can have. Her first clue that she might have some hidden genetic vulnerabilities came during a surgical procedure as she was giving birth when she was given Percocet. It had absolutely no effect on her pain.
That process repeated itself during an emergency dental procedure when she was given Percocet, once, twice, three times – and received no relief at all (nor experienced any side effects). She might as well have been eating sugar cubes.
A week later, she went back for another procedure and asked to be given Darvocet which knocked her pain levels out. Subsequently, she found out that genetic polymorphisms in her CYPD26 (or 2D6) gene left her unable to metabolize Percocet. (Ten percent of Caucasians are 2D6 deficient).
Years later, her son, who was also 2D6 deficient, was scheduled to have his wisdom teeth removed. Requesting that hydrocodone, which his genetic status suggested that he metabolized poorly, not be used, didn’t work. Stating that, “of course, he (the surgeon) blew me off”, her son got little relief from the hydrocodone, went back to the surgeon complaining of pain, and was labeled a drug seeker.
Take codeine. Codeine is inert – by itself it has no effects on pain – and has, like many opioid pain relievers, to be metabolized to morphine by the CYP2D6 enzyme to work. Morphine is then metabolized by another enzyme called UGT2B7 to M6G (morphine-6-glucuronide), which has pain-relieving properties. During that metabolic process, though, two other factors are released which can actually increase pain levels.
If you are not metabolizing codeine, you will get little relief from it. If you’re a super metabolizer taking large amounts of codeine, this could actually make your pain worse. Trescott relayed the story of a child with testicular cancer, in terrible pain on 1,000 mg of morphine, but whose pain was under control on just 30 mg. At 1,000 mg, the child’s system was being flooded with pain-enhancing metabolites. At 30 mg, his system was getting morphine and it was working.
Hydrocodone is similar; by itself, it has very little effect, but when metabolized by CYP2D6 to hydromorphone or Dilaudid, it relieves pain. If you find that hydrocodone doesn’t work for you, but Diluadid – which doesn’t get metabolized by CYPD26 – does, you may be genetically designed not to be able to break down many opioid painkillers.
Tramadol – a weak opioid commonly used in FM – is also metabolized by CYP2D6, but in a twist, the same enzyme also controls tramadol’s excretion. If you’re not so hot at metabolizing tramadol, you may end up with poor pain relief plus lots of side effects due to poor excretion.
Small changes in genes, called polymorphisms, can sometimes alter their functioning.
For the past five years, codeine prescriptions for children have been restricted because of the effects CYPD26 polymorphisms can have on children. The same concerns have lead the FDA to recently release a boxed warning for the use of Tramadol in children. (The problem is probably only relevant for children with a certain genetic makeup, but in them the effects can be severe. Trescott relayed the story of a child with rapid Tramadol metabolism who ended up in a coma in the hospital.)
(Tramadol is metabolized by several enzymes, and because it’s an SNRI, is good for neuropathic pain. The lecturer said it was one of her favorite drugs for pain.)
(Genetic polymorphisms or mutations could even be responsible for the removal of drugs from the market that could have been helpful for many but which harmed people who were unable to metabolize them properly.)
There there’s methadone, which the doctor called her “desert island” drug. At its best, it knocks neuropathic pain out, often causing no side effects at all – a rarity with painkillers. Breaking down methadone is a complicated process, however, and her patients have varying responses to it. When it works, though, it really works.
If your CPYD26 status means you’re not going to get much relief from the “odone’s” (hydrocodone, oxycodone), Tramadol or codeine, there’s still hope. You might do just fine on morphine which is metabolized differently.
Antidepressants
The same process occurring in pain drugs applies to antidepressants and other drugs. The CYP2D6 enzyme metabolizes about a quarter of commonly used drugs including many antidepressants. Genetic polymorphisms have so impacted the response to antidepressant drugs that a 2013 Consortium has produced guidelines for antidepressant drug dosing (amytriptyline and nortriptyline), depending on what genetic variations are present in two genes (CYP2D6; CYP2C19).
Its low cost has made Amytriptyline a popular drug, but Trescott called it a “dirty drug” with a lot of potential side effects, in part because of problems some people have metabolizing it.
Drug Interactions
Drug interactions are another really good way to affect drug metabolism. Trescott relayed the result of a study which found that if you’re taking six pharmaceutical drugs you have a 94% chance of a drug interaction occurring; i.e. one of those drugs is going to impact how at least one other is functioning.
Because Paxil, Prozac and Duloxetine inhibit the CYPD26 enzyme, taking them could make your pain drugs less effective. Taking those drugs together could effectively turn a normal CYP2D6 metabolizer into a poor one. (Celexa and Lexapro, on the other hand, do not inhibit opioid painkiller metabolism).
If you happen to be taking benzodiazepines, tricyclic antidepressants, naloxone or diclofenac — and morphine or its derivatives — watch out because each of these drugs enhances the breakdown of morphine to metabolites which enhance pain levels! (If you’re taking opioids, getting off benzodiazepines might help them work better.)
Note that St. John’s Wort – a herb sometimes used for depression – is a potent CYPD26 inhibitor. If you’re taking St. John’s Wort and your pain, antidepressant or other medications stop working as well, St. John’s Wort may be the reason.
Even something as innocuous as cinnamon can be a problem. Cinnamon can cause oxycodone to metabolize into a substance which doesn’t have strong pain-killing properties.
Some drugs can alter how other drugs are metabolized.
All over-the-counter stomach medications are not cut from the same cloth. Taking methadone and Rantidine together is fine, but if you take Cimetidine and methadone you could end up in the hospital because Cimetidine inhibits the metabolism of an enzyme called 34A which breaks down methadone.
Because cannabinoids are probably significant inhibitors of the CYP2C19 enzyme, which breaks down Valium, Soma and several antidepressants, people taking cannabanoids may notice changes in the effectiveness of those drugs.
COMT, Fibromyalgia and ME/CFS
Dr. Trescott’s last story involved a gene called COMT whose polymporphisms have been associated with an increased risk for fibromyalgia and chronic fatigue syndrome (ME/CFS). The research on COMT and FM is pretty extensive with the latest study coming just this year.
A 48-year-old male with attention deficit disorder, obstructive sleep apnea, polymyalgia, post-traumatic stress disorder, and chronic low back pain stated he was not responding well to his antidepressants or his ADD medication (methylphenidate) which blocks norepinephrine and epinephrine uptake. An SSRI gave him terrible headaches.
Genetic testing revealed he had reduced COMT activity. Because COMT breaks down serotonin, norepinephrine and epinephrine, his high pain levels were understandable.
Testing also revealed that he had reduced activity of the enzyme that converts methylenetetrahydrofolate to folate, and reduced folate levels, it turns out, are associated with reduced responses to antidepressants and pain medications.
Giving him a folate booster (leucovorin 10 mgs/ morning) and zinc sulfate resulted in a rapid decrease in his pain scores from 9-10 to 2-3 in a week. Plus, his depression and ADD improved.
Hypersensitivity Reactions in ME/CFS
Other scenarios in which genetic testing may be useful include patients who have shown a poor response to medications in the past, those with a family history of drug sensitivity…Argarwal et. Al.
One wonders if the hypersensitivity to drugs and strange drug reactions that some ME/CFS patients experience could be due to a genetic issue or to an epigenetically induced alteration of D26 or other metabolizing genes which occurred when the patient fell ill.
I, for instance, have become extremely sensitive to caffeine. Just a few sips of coffee or tea can send me flying. That didn’t happen prior to ME/CFS. Polymorphisms in two genes (CYP1A2, N-acetyltransferase 2) mainly regulate caffeine metabolism. Could an epigenetic shift have turned me into a super caffeine metabolizer?
Testing
Pharmacogenetics is a relatively new field which uses genetic tests to assess a patient’s risk of having an adverse reaction to a drug or their likelihood of responding very well to it. It’s too new for most primary care doctors to be aware of pharmacogenetics, but a primer was recently published that could help guide their use of opioid painkillers. It’s been estimated that over 25% of common drugs have some sort of genetic information which could prove useful.
Genetic testing can provide some answers, but unfortunately is usually not covered by insurance – a mistake, Dr. Trescott thinks, given the 2.2 million adverse drug reactions in the US that cause 100,000 deaths and cost the medical system billions of dollars every year. A variety of genetic panels (CYP2C9, CYP2C19, CYP2D6, and VKOR1, OPRM1, COMT, and ABCB1, as well as dopamine receptors and transporters, serotonin receptors and transporters) are available, however, and more are on their way. Trescott mentioned that Generex [SP] has a program which combines genetic test results with drug intake to determine which drugs are more likely to help.
A group of largely U.S. researchers has created a “Genetic Addiction Risk Score (GARS)”, which uses variations (polymorphisms/mutations) in ten genes to determine one’s risk of having pain problems and/or increased drug or alcohol use. They’ve warned about commercial enterprises which offer bogus gene testing, claiming to be able to predict addiction. See the strange case of Proove Biosciences.
As costs of genetic testing continue to decline, genetic tests at a reasonable price should become more available.
Bottom Line – Doctors Should Listen to Their Patients!
“When they say they’re not getting relief from their medicine, they’re not getting relief from their medicine. Okay?”
The bottom line for Dr. Trescott is that doctors should listen to their patients. If a patient is not responding well to pain or other drugs – if they feel they need more drug to get relief (low metabolizers), they’re not necessarily drug seekers. Or if they’re getting lots of side effects (rapid metabolizers), they are not necessarily complainers or hypochrondriacs.
Pharmacogenetics is being used in cardiovascular disease, and extensively in cancer, but not so much in pain yet. As the research proceeds, though, and the data builds up, it will play a key role in the personalized type of medicine that our medical system is slowly moving to.
I had a horrific experience with Prozac when a Dr prescribed it as a possible “help” for my Fibromyalgia. The most horrible physical feelings of depression started to increase over the first few days, a “black hole” down in my stomach and loins. At first I thought this was real “depression” but when I took the next dose of Prozac a little early “to see if it helped”, it quickly became clear to me that the Prozac was the CAUSE.
Mere depression is nothing on my experience that night. It was like the black hole in my lower parts had grown outwards to become a huge black hole suffocating me from outside. Lying on my back in bed, it felt like I was being crushed from above, more of a hallucination than actual pressure, and yet it seemed as real as anything physical. I writhed around, got up and moved around, trying to lose it, but it came with me.
I fully understand why there is a hypothesis that Prozac causes suicide in some. The urge that was pushing itself on me, was to throw myself straight out through a glass window two stories up in desperation to escape the sensations. The idea of slamming myself hard into the ground, or at least a wall, had a certain perverse attraction.
There is an interesting medical term for this experience – “Akathisia”.
“…extreme restlessness and an inability to sit still. The discomfort can be so great that suicide becomes a welcome alternative to feeling this type of agitation. Sometimes akathisia is misdiagnosed as worsening depression, so medication dosage is increased, causing the restlessness to persist…”
http://www.drugwatch.com/ssri/suicide/
“Restlessness” is far too mild a term, but the point about suicide makes it clear.
I am thankful for the strength of faith that brought me through that night. I ceased the Prozac immediately and the “depression” relieved. Since then I have not been bothered by any “normal” depression symptoms because they are nothing to what I experienced that night.
I emailed a number of family members about my experience, and an elderly aunt replied: “SSRI’s do NOT suit us Haywards, every one of us who has been prescribed them has suffered something like that”.
I had this too. After only 36 hours on what I was told was a low dose I felt completely insane. Extreme agitation and dreadful physical sensations. I felt like I was jumping out of my own skin. I can remember looking out of an open window and getting impulses to jump. Thankfully I realised and I stopped the drug. I have never felt like it before or since. I have heard of these drugs causing suicide and being responsible for men murdering their wives. Awful dangerous stuff – much more needs to be known before prescribing.
I also over react to coffee b vitamins ubiqunol. Am very sick with codeine and general anaesthetic.
Most doctors would rather guess and prescribe a med “to see if it works.” There are genetic tests available that will quickly identify which med(s) is(are) a correct fit for their patients, but I found out that “Come back and let’s see how it works” visits are lucrative for doctors and don’t want to use these tests.
I found out because I was a rep for a genetic test company, (I won’t name company because I don’t want to dilute my point) and I could not get ONE doctor interested. Also, pharm companies pay well for drs. to default to their products as a first choice.
Side note: I was so geeked when I first learned of these tests; I thought they were the new modern day marvel! Big Pharma (including drug stores) is alive and well. You may have already heard, CVS bought Aetna-not the other way, folks, the drug store acquired the insurance company!
Cort I am so grateful and thankful you have written about these enzymes. Since I have become ill with ME/CFS, I have noticed that I have become very sensitive to medications, medications that once I could take a normal dose now I only need 1/4 to have the same effect. I have also developed MCS, multiple chemical sensitivity, and have severe reaction to many chemicals that I did not have before developing ME/CFS. I have discovered through testing that I have a gene variant of the CYP2D6. In my research I have found that the series CYP450 enzymes are not only responsible for metabolizing drugs, but also responsible for eliminating chemicals and other toxins (biological). I was exposed to toxic mold that gave off mycotoxins. If grapefruit juice and St. John’s Wort can affect the CYP450 enzymes, could the mycotoxins do the same? Could the toxins given off from bacteria and viruses also impair enzymes? Is it possible that toxins from infections like EBV or HHV6 be causing the enzymes to be impaired or a result of impaired enzymes? Also, I found out these enzymes are in the liver and small intestine. Are you aware of any test for the liver or intestines enzyme function? Could our toxic elimination system be broken? Thanks again for all that you do!
Good questions. It does remind me of this thing I read about painkiller paracetamol and glutathione deficiency: when glutathione is depleted, paracetamol (still a main painkiller for FM over here despite it being far too weak for us) can become very toxic. As many FM/ME patients have glutathione deficiency (due to too high oxidative stress IMO) I avoid paracetamol since then as the plague just to be sure. No need for additional toxic effects on my liver.
So I searched “CYP2D6 glutathione” and found that this gene has a strong effect on glutathione S-transferases. Glutathione S-transferases is important in recycling glutathione, the bodies strongest anti-oxidant. That leaves some implications:
* CYP2D6 gene malfunctions may cause oxidative stress over- or under-expression. As FM/ME are believed to involve high oxidative stress levels this gene malfunctioning may be overrepresented in FM/ME.
* Using medication that requires this gene’s enzymes may compete with glutathione / oxidative stress handling. So using these (or 25% of all medications) could help impair oxidative stress response. It’s unknown if oxidative stress would be more of a cause or a consequence, but further depleting glutathione unlikely is a good idea. Mapping FM/ME patients gene for this CYP2D6 problem and generally map which medications interact with it *might* therefore in itself be of good help for us if medication could be replaced with non-interacting variants. As money is tight with many of us, maybe they should be tried first if a test is too expensive.
* A disease with high levels of oxidative stress should consume high amounts of enzymes produced by this gene, leaving less for medication depending on it. So even if this gene worked normally it could affect 25% of medications in FM/ME patients. That’s why I favored trying “non-CYP2D6” medications in FM/ME patients in previous point. When a patient has this gene defective it could be a double hit.
* As both this gene as well as glutathione deficiency both interact and affect detoxification of a wide class of chemicals ranging from heavy metals over pesticides http://journals.sagepub.com/doi/abs/10.1177/0891988714522698?journalCode=jgpb to drugs, it should be normal for FM/ME patients to have decreased detoxification rates and increased chemical sensitivities.
See also https://www.ncbi.nlm.nih.gov/pubmed/24584466 : CYP2D6 mutations affect chance for Alzheimer disease. Somewhat surprisingly: “The significant low level of magnesium (OR = 0.151, 95% CI = 0.047-0.489) even appears to have a protective role against AD”. That may be quite important for us. Alzheimer disease is believed to be an oxidative stress disease. As I wrote elsewhere, magnesium is a good uric acid remover if local concentration gets too high (local, not measured blood values that can be simultaneously low). But uric acid is the biggest source of anti-oxidant in our body. It’s less effective then glutathione, but available in far higher numbers. So while magnesium helps many patients (maybe by removing too high local uric acid concentrations IMO), it helps lower uric acid in blood and hence anti-oxidant concentrations. With combined low glutathione levels the picture may become troubled.
As to paracetamol: it’s effected too by CYP2D6 http://www.mcppnet.org/publications/issue06-6.pdf.
A last interesting note: “The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids.” (note on naming in paper: CYP2D6 is cytochrome P450 family 2 subfamily D member 6) from https://www.ncbi.nlm.nih.gov/gene/1565
What’s important about that? Many FM/ME patients claim to have low cholesterol levels. That surprised me as mine is quite high without meds. (And I am very “good” at making huge amounts of triglycerides (“other lipids”) too). But it could be related once more to this CYP2D6 gene. It also encodes steroids, like testosterone. Testosterone is mentioned to be effective in MS (likely another partially oxidative stress disease), maybe in ME and testosterone is believed to reduce oxidative stress levels.
I did not find improvement in testosterone supplementing (it’s effect may have been overcast as I was prescribed 3 other hormones as well). I however have too high cholesterol/triglycerides levels so I may be a quick metabolizer. Wouldn’t be surprised as I do often well on very low doses of meds (with few side-effects as long as doses are low) and I have *very* quick response to some meds, close too “it is psychosocial, these meds do not work so fast type of doctors comment”. I also happen to have very few known chemical sensitivities or allergies (none worth mentioning).
I also happen to have very high pain tolerance as opposed to decreased pain tolerance as most FM patients are *believed* to have. Maybe this gene also activates/deactivates the “body-own” painkillers? If that would be true, it could again point to very high rates of CYP2D6 malfunctions in FM/ME patients.
Thanks, Cort something I have wondered about for a long time. Particularly since being diagnosed with ME/CFS 15 years ago. I am very sensitive to certain medications, foods, additives & chemicals.
This article has given me further insight into these issues, thanks again for your good work keeping us all up to date.
^^^^^^^^^
What Dee said 🙂
Cort. Once again your work is wonderful and I have suspected this low vs high metabolism being hard wired into us for several years. Where is reliable genetic testing for this? Again thank you so much for the information!
Like you Cort, I also do not tolerate coffee or tea, (even decaffeinated coffee and tea). I read that if you have a slow COMT (Catechol-O-methyltransferase) gene / enzyme, that it doesn’t process catechols very well, which are in tea and coffee, and when I looked up other foods that also contain catechols, there were 2 others that I do not tolerate very well, being chocolate (I was eating pure cocoa mass drops with no other added ingredients) and prunes, both of which are high in polyphenol antioxidants and I love – and so thought would be good for me!
Dr Ben Lynch is a ND (naturopathic doctor), whose recently published book ‘Dirty Genes’ looks at seven common genes, including the COMT gene, and how one can help shift them back to a more ‘helpful / normal’ expression with diet, and you don’t have to have had a gene test to do this. From reading his book it seems that I may have a slow COMT gene, so it was very interesting to read that an MD (medical doctor) also suggests that the COMT gene is associated with ME/FM. Dr Lynch has a useful starter video to help understand genetics / epigenetics / nutrigenomics on youtube here; https://www.youtube.com/watch?v=6OCqDvoplOQ.
I recommend reading his book ‘Dirty Genes’ with a copy of his ‘Pathway Planner’. It shows the biochemical pathways of how a gene / nuerotransmitters / hormones can become blocked and what nutrients / cofactors are needed to facilitate the pathway to work efficiently. However I do not recommend looking at the poster without reading the book, as he stresses that lifestyle factors are a big component in making genes work for or against you. The Pathway Planner poster is for Doctors and costs $199, but you can google image it, or find it on Pinterest, I printed an A4 copy from here; https://www.pinterest.co.uk/offsite/?token=869-449&url=https%3A%2F%2Fi.pinimg.com%2Foriginals%2F2f%2Fff%2F99%2F2fff997a06af120e2f5f55deaf2cea60.jpg&pin=1407443609145432&client_tracking_params=CwABAAAADDI2Nzk3ODc3NTMxMQA
Pharmacogenomics. I can’t wait for the day when we have individualized medicine. Way to forge the way, start the conversations, bring the science and patients to the same table. Thank you.
🙂 The sooner it gets to FM and ME/CFS the better 🙂
I am in agony. Been there a very long time. Whenever I assertively ask for help with pain, doctors give me that look. You know the look – it’s the one that winds up in their notes regarding drug seeking patient. Finally things reached the point where I had to pretend to be an addict to get pain relieving opiates. And subsequently to the present suffering madly on suboxone while tremendous relief comes with pregabalin & lower dose suboxone. Problem is doc won’t give me enough pregabalin and amount that works for me is roughly 3x max allowable.
After reading this I backtracked to a few people and ME orgs on social media so maybe there is hope. Thank you.
Interesting; I stopped being able to tolerate caffeine lately, too. Even tea.
I don’t respond to morphine but do to Dilautid (I know this from ER). I knew about polymorphisms but forgot and thought it was because the other was stronger.
Thanks for the good article.
I have exactly these types of problems with opioids. Most make me extremely sick and don’t relieve any pain. Only one didn’t make me sick, but it still had zero effect on my pain. Doctors were shocked that I didn’t even get sleepy, with that particular drug. I’ve lived in fear of needing another surgery, knowing I’d have no pain relief. Too many doctors pushed opioids even though I told them of these problems. Fortunately, tramadol does work for me, but I can’t tolerate it frequently, due to other side effects. Also, it’s not strong enough for surgical pain.
I also had a unbearable headache with one antidepressant that was prescribed for my fibro.
Thank you, Cort for another invaluable article. Please consider passing along any further info you find on this subject.
This is really interesting. I’ve suffered for many years with unusual reactions to many medications but no one I’ve spoken to can quite understand it.
Does anyone have a link to any research that has been done? It would be much appreciated and I’d like to be able to provide information to GP’s etc.
Your article mentions the “Strange case of Prove Biosciences” I was one of the ones that was strongly recommend to participate in this research study by my pain management doctor. In fact after the initial mouth swab, I was drug tested and asked a series of questions monthly for several months. I questioned this testing and was in fact very hesitant about having to participate in this, especially after being told the test would be able to tell if we were “genetically predisposed to being addicted to drugs and alcohol”. I was not given much choice about participating in the testing. I later learned that not all patients were required to participate in this testing, it depended on what type of health insurance you had, as Proove proceeded to bill my health insurance for more than $20,000 the last time I bothered to add it up. I was extremely upset when I learned that they were charging my insurance company for what was supposed to be a research study, I course when I addressed it with the doctors office and my insurance company, neither party seemed as upset about as I was, so I ended up letting it go. I don’t find it at all shocking to hear that the results have been found to be bogus. I think they should face criminal charges for this type of stuff. I cannot imagine the amount of money they made putting false “levels of addiction” on innocent people.
Fantastic article Cort! Answers alot of questions for me. However, I’m confused about taking CBD’s; will this make my Soma and Xanax work better or worse?
Also, does anyone know the pricing of these “at-home” genetic tests? Sounds worth it..
Hi. Should have a CBD oil (is that the question?) I don’t know about the interactions but CBD oil can really help. Hopefully a blog will be up in the near future..
Your reaction depends on your genetic makeup, ie whether or not you have a polymorphism and which ones. At this time I don’t think there are any reputable at home tests available. Some insurances do cover it. You have to ask, and sometimes you have to fight as they only cover it under certain circumstances. The two most common are ADHD and to prove you’re not drug seeking.
After I had been through 4 stimulants in 5 months to treat a sleep disorder, with no affect at the highest dosage, the pulmonologists nurse took pity on me when I called in tears and referred me to a doctor she knew at a counseling center that specializes in such issues. He convinced my insurance to pay to prove I wasn’t drug seeking. The testing isn’t perfect because it’s still a limited number of genes that are tested, but it’s a far underused tool that can be used to narrow things down, and in some cases fully explain a med issue. It was immediately obvious why I do not process any of the commonly prescribed stimulants. That then allowed me to make a case for a brand new one that is processed differently that my insurance does not normally cover. If your insurance won’t pay or your doctor isn’t affiliated with the testing, a website called drugbank.ca has thousands of drugs with tons of info incl the targets and enzymes, which is the pharmacological info. You might be able to identify a potential issue with a bit of research. By looking up the targets and enzymes of meds you’ve taken in the past, you may identify a pattern you could then discuss with your doctor.
Thank you so much for publishing this article. The more this information is presented to the public and discussed, the faster we can get doctors and insurance companies to accept and support it. I was lucky that my insurance company covered it to disprove drug seeking. When we got the results, it was obvious why I was not processing the stimulants normally prescribed for sleep disorders.
I also have fibromyalgia, but had not been aware of the COMT connection, so thank you for including that information. Additionally, I have the issue with processing folate and have been very frustrated that insurance will not cover prescriptions except for pregnant women, even with the genetic testing that showed that I actually do need the prescription formula. Here again, the more we make this information publicly available, the more likely we are to get the help we need.
I will be sharing this article to Facebook and to PatientsLikeMe, an online website where patients can enter information, track symptoms, make private notes, and participate in a community forum for support. I am a huge advocate for this kind of testing becoming as common as CBC Blood tests. So many improvements could be made in the field of medical treatment with the advancement of this testing.
Fibromyalgia attacked my mother body more than 3 years ago after her knee surgery. She has been in a wheelchair for about six months, and she used a cane for another six months. She did not even know how to walk anymore. We fought the fibromyalgia with a lot of pain pills and tears not until we had to give a try on natural formulas, we purchased a herbal treatment from totalcureherbsfoundation.com which help her a lot and bring her back to normal again, the herbal formula reverse the symptoms grammatically and she’s totally free from the Fibromyalgia that cost her pains for ages .
I find this particularly fascinaating for a couple of reasons: a lifelong history of weird drug reactions (really dire strange reactions, or supposedly “strong” drugs that had no effect whatsoever –anti-anxiety meds do nothing at all, opioids have very variable effects, etc).
I have found that hydrocodone works as well for me for my several sources of chronic pain as any other opioid, & I’ve tried nearly everyone in the last 4+ decades. My doctor announced at my last appointment that no one with fibro should ever, ever, be given any opioids whatsoever. News to me; it helps my several pain issues, & I’ve never actually been diagnosed with fibro. I sorta might have it maybe, & apparently that slight possibility is the new reason I must come off my pain meds at all…despite the fact that I had to go without them for a couple years a few years ago & was basically in so much pain i couldn’t function.
I assume it’s just the Church of Opiophobia’s preachings getting ever more powerful & gaining new zealot converts. I can’t begin to afford genetic testing, tho I wish I could.
Dear Dr. Trescott: I am an ultrarapid metabolizer – one normal allele and 1 abnormal duplicating allele. NO opioids have ever worked for me. I went through a c-section, 4 wisdom teeth being pulled, ulnar surgery, breast reduction – many surgeries – with no pain relief. I tell my doctors that I have awoken in the middle of every single surgery I have ever had, and NOBODY believes me. They automatically assume that I just want more medicine. Until, of course, I wake up in agony in the middle of the surgery panicking the surgeon and anesthesiologist. Again though, I am the one that suffers.
Now that I know why, and what two genetic research scientists have explained to me, as well as multitudes of research I have done myself (35 yrs medical trial paralegal) and, which is completely logical to me, opioid medications go through an ultrarapid metabolizer SO FAST there is no time for analgesic relief, no time to build up in the body, no time to cause side effects, etc.
This has certainly been the case for me since I was 10. (I am a DES daughter and have had multiple, continuing, painful issues up to and including this very day. Severe post-menopausal endometriosis and now an endometrioma, yet I have no pain relief whatsoever because I can’t find a doctor who even knows what an ultrarapid metabolizer is, let alone what it means and how it affects prescribing.
I am suffering because of the ignorance of doctors who do not keep up with medical advances. And just want to label you. I can’t tell you how many times I have been told, “yeah, RIGHT. Come see me when you get your MD!” This, even after I show them my pharmacogenetic test results and explanations, I am still labeled a “drug seeker.” And if they do, by some miracle, undertake even a modicum of research, running across an article like yours just makes the situation worse. Are there no papers, no seminars, no urgent advice to pain management doctors and anesthesiologists that would update and EXPLAIN this new, state of the art, precision prescribing? I can’t find medical treatment, I can’t get any pain medication. NO doctor here gets it.
Part of the problem is articles like yours. For every 100 articles and opinions that say an ultrarapid metabolizer, i.e., FAST, doesn’t metabolize opioids, all they need to do is run across one article like yours, that gives them room for doubt and that’s it. Confirms their doubt. You say that an ultrarapid (FAST) metabolizer has buildup of drugs that cause serious, even fatal symptoms. This is the description of a POOR metabolizer I believe. Medication is metabolized so SLOWLY, it collects to a potentially lethal level, creating side effects. My test results say I am an ultrarapid metabolizer. Opioids just fly through my body and there is no time for analgesic relief.
Opioids are not activated by CYP2D6. I’m sure you know that. My life experience reflects that. Yet I suffer daily, DAILY, even as I sit here right NOW. In severe pain.
I broke my back in 5 places in 2011. I broke 8 ribs in a fall in 2012. I have two torn rotator cuffs. I have painful scoliosis. I have knee replacement that the doctor botched. Doctors say, “you need long term pain management.” Easier said than done. In fact, impossible. All they will give you is Norco, Tramadol (???), Vicodin, etc. Over and over. Sugar pills.
I cannot find ANY pain doctor within 200 miles of my home that will even SEE me because the four or five medications that WILL work for me are morphine derivatives and I when tell them I was on the Duragesic 75 mg patch for the last 11 years with no side effects whatsoever, just blessed pain relief, they have actually said that I was the most creative drug abuser they had “seen yet.” And after YEARS of trial and error we FINALLY found a drug that worked for me, with total pain relief, but now I’m a drug seeker.
I refuse to have pills in my house. I am terrified about becoming addicted. I was raised right. I have never smoked, drank or abused drugs. But I am being treated as a pariah. A drug addict. People like you are perpetuating this misperception and people like me are SUFFERING. Personally, I am at the end of my rope. If I can’t find a pain doctor that will accept this precision prescribing evolution, it’s just going to kill me.
You know, if you could correct this and possibly write SOMETHING to my doctors explaining this in very SIMPLE medical terminology, maybe, just MAYBE, we could educate some pain doctors who should know better and I could get some pain relief, back on the medication that has worked or 11 years, the Duragesic patch. They are all so afraid because of the CDC GUIDANCE,
An afterthought: I don’t suppose you treat people virtually and mail rx’s? I’m desperate here… Kathleen Lawler 239-689-0282
Respectfully submitted,
Kathleen Lawler