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The Carlat Psychiatry Podcast
"donner becker" Discussed on The Carlat Psychiatry Podcast
"The human genome was mapped in two thousand and three and with. It came the hope that we could one day taylor. Treatment to a patient's genetic fingerprint. The white was not long. In two thousand and five the first pharmacopoeia. Genetic tests were released for the metabolic enzymes. Cyp two d six and cyp to see one nine. Those tests were approved by the fda but most of the commercial genetic panel said of cropped up since then are not approved and that difference is important to understand when we talk about genetic testing. We often talk in. Black and white terms like is genetic testing useful or not. That's a bit like asking is laboratory testing and psychiatry useful or not clearly. The answer depends on the patient and the test involved so while individual tests like cyp tutti six and to see one nine are fda approved most commercial genetic panels like the ones that draw promotional literature. Your office are not approved and not generally recommended by experts. One of the most prominent of these is gene site which was released in two thousand nine gene site with developed by people from male and then it was commercialized through it. Sure acts and then assure acts was sold to marry a genetic which is a huge corporation. So now it's certainly commercial but it was developed by academic investigators and there's a paradox with genetic testing. Well individual tests might be sound when you pile bunch of those together in a pharmacogenetics panel. Not so much in the carlisle report. We've covered half a dozen studies that tested these genetic panels out in real world populations usually impatience with depression. Who failed to respond to an antidepressant. Now you would think that was an enriched design that if you're going to see a strong signal with pharmacogenetics testing it's in people who didn't respond well to anti-depressants that these tests automatic difference the time and again they full show it. We covered one of those failures. Some in a large trial of the gene sipped test. So what is going on. If some of these individual tests are valid. Why do the genetic panels failed to work well. They don't exactly fail to work. When you stack all those failures up you do see a small signal pointing towards successful outcomes with genetic tests. The meta analyses of pharmacokinetic genetic tests are actually looking pretty favorable recently. Not the ones on the snl lille of the serotonin transporter which have been more or less negative than the ones on the cyp enzymes particularly to six and to nineteen are looking pretty good at at this point and i participated in one of them a few years ago and i was impressed with the care that they took and designing the protocol and i think it was good study this month. We interviewed john. Nuernberger about which of the dozen or so genes in these pharmacogenetics panels are useful and which ones to take with a grain of salt their genes. That would be most important would be cyp to six and to see nineteen little bit. You know. three four sometimes gets thrown in. But mostly you're looking at tuten six and to see nineteen grants the presence and and so when i look at the report. That's what i'm mainly paying attention to. And i'm i'm also paying attention to the broad recommendations of go which medications particularly avoid you take with a grain of salt. But there's you can see where the evidence i'm from and i'm particularly interested in than saying that evidence for two d six to see nineteen dot number recommended. Cyp two d six and to see one nine and those are the same tests that were the first gain fda approval in two thousand and six. Those are the top two an online interview. He delves into other genetic tests that deserve a place at the table but whether the test is useful or not depends a lot on the patient. Here's what datta nuremberger thinks. Genetic testing has the most utility. I think it is worthwhile centering. Genetic testing for individuals that have a failed couple of antidepressant trials or individuals where. There's other reasons to think they may be having very unusual responses to to medication. And sometimes it's it's very useful for the patient to get that kind of information and feel as though there's a reason for them to understand their their experiences with medications. I don't follow the directions rigorously. But i think the evidence suggests that if you have a test that gives you like a green light yellow light and a red light for the medications. It's probably wise to avoid those that are in the red light category. You can use the others with some adjustment of dotes and just being careful with them with the dosing in the interview. Donner becker discusses the relative merits of ordering individual genetic tests sticking only to the most high yield ones versus ordering a whole genetic panel these days many patients coming to their first appointment with the results of one of those genetic panels already in hand. So let's unpack. What is inside these tests. These tests fall into two board categories pharmacokinetic tests these. Tell us something about the blood levels of medication whether they are likely to go to high to low around. Twenty percent to thirty percent of people have genetic variations in their metabolic enzymes and these can lead to abnormally high. Paul metabolisers olo rapid metabolisers levels of psychiatric medications most pharmacokinetic tests focus on the genes. That code for these enzymes those tests look at the enzymes in the liver and there's a whole nother type of pharmacokinetic test that looks at the blood brain barrier just as deliver determines the serem level of many medications. There's a pump at the blood brain barrier called. Pete like oh protein transporter that determines the level that medication will reach in the brain peed like oh protein. Regulates the transfer of medications across the blood brain barrier and some medications are more susceptible to variations at this transporter than others. Only a few commercial tests. Look at this gene but it is one of the more practical ones.