Antidepressants Get Personal, So Be Happy
Katherine Mangu-Ward | June 19, 2007, 11:02am
"Within a few years," says The New York Times, personalized depression drugs will be the norm. A recent study published in Science suggests that certain identifiable genetic mutations may predict reactions to common antidepressants. "Nearly all drugs are metabolized by a group of enzymes that vary greatly in activity from person to person. If patients have a genetic mutation that results in either deficient enzyme activity or none, they would be likely to have serious side effects if exposed to the drug that is metabolized by the enzyme."
This is particularly heartening in light of recent stories about a greater suicide threat for some teens on Prozac. This is exactly the sort of pharmacological incompatibility that may be solved in the near future:
Instead of the hit-or-miss approach...it will soon be possible for a psychiatrist to biologically personalize treatments. With a simple blood test, the doctor will be able to characterize a patient’s unique genetic profile, determining what biological type of depression the patient has and which antidepressant is likely to work best.
More on psychoactive substances from reason here and here.
Bronwyn | June 19, 2007, 12:37pm | #
If I may use a Fark cliche, I am a geneticist working in a pharmacogenetics lab and I'm really getting a kick out of your replies.
No, really. I am and I do...
In fact I am at this very moment optimizing a protocol to test for a variant in the promoter of the serotonin transporter gene. If I may expound for a couple of minutes, I will tell you how this works.
The gene has a length variation, called a polymorphism. Some people have a long version, others have a shorter version - the difference is only 44 base pairs long, but it makes a 2-fold difference in gene expression.
This is where the layperson's eyes tend to glaze over, but it would be really great if everyone could understand this so please bear with me.
Folks with the Long version express the gene more than the Short folks. This means that Longs have more efficient serotonin reuptake than Shorts.
Antidepressants like Prozac and Lexapro and so on inhibit serotonin reuptake (SSRI stands selective serotonin reuptake inhibitor).
Put this together... Longs are sucking up the serotonin like a Hoover, so there's lots of room for improvement. Therefore, Longs on SSRIs tend to show greater improvement in their depression scores than do Shorts. It so happens that, although both Longs and Shorts can be depressed or have PTSD, the Longs tend to have worse symptom scores in certain categories than Shorts. The scoring for these things is mind-bogglingly complex and it often sounds like gibberish to me, but that's because I'm a molecular biologist, not a psychologist - so let's just leave it at that.
So. Longs may suffer more from certain symptoms, but they have plenty of room to improve, so the drugs work.
The Shorts are the opposite. They've got plenty of serotonin floating freely already, so there's little room for improvement with SSRI treatment. They may be depressed, but because their depression isn't due to a lack of serotonin, an SSRI is useless.
Now here's the scary part. SSRIs can have lots of bad side effects and Shorts are far more susceptible to these side effects than Longs. Therefore, it's really unwise to treat a Short with an SSRI - they're less likely to see a benefit and more likely to see a lot of side effects.
The metabolism genes, which determine whether and to what degree a drug will build up in your body or pass right through, understandably will also have a significant effect on whether a drug will help or hurt you.
We can put together profiles of these genes and get a pretty good picture of what will work for you, whether you'll suffer side effects and how bad they'll be and so on.
This is what the company I work for is all about. The roadblocks are many, but the two biggest ones are: (1) physicians aren't trained very well in genetics and they're eyes glaze over almost as quickly as any layman's so they are slow to accept these concepts, much less agree to adopt them into practice and (2) drug companies spend billions of dollars creating and marketing drugs - they have little interest in finding out that their drug will only work for x number of people or that it might kill y number of people.
Celebrex is a great example. It works and it works very very well, but a small percentage of people have a certain genetic variation and celebrex tends to kill them. The drug was yanked from the shelves because of these people and because pharmacogenetics has not yet been adopted into standard practice.
Yet. The FDA is finally figuring this stuff out and Barack Obama, for all his faults, has introduced legislation to encourage more study in pharmacogenetics.
I'll shut up now but will happily expound further if anyone would like to hear more.
Bronwyn | June 19, 2007, 2:12pm | #
poco - excellent - that's precisely what I'm looking at. As it happens, l/l and l/s are typically put together in the same category, as (L)ong carriers versus (S)hort carriers because the long appears to have the dominant effect.
I've been seeing more articles on the topic too, and I'm glad to know people are paying attention. People can be skittish about their genes, particularly when it comes to using genetics to indicate disease risk. No one wants their insurance company or employer to know that they carry a gene variant that makes them more likely to have some chronic and expensive disease.
We tread a fine line with this. Researchers can play all they want with linking genes to disease risks (obesity, heart disease, cancer...) but few others will touch it with a ten-foot pole.
Reinmoose- I've had my troll moments, believe me, but when it's a topic so close to my heart, I try to be good :)
It pisses me off to see headlines like "personalized drugs" because it's absolutely inaccurate and misleading. This isn't about personalizing drugs at all, it's about personalizing treatment. A physician shouldn't just whip out their PDA and rubberstamp prescriptions any more. There's no excuse for it.
And you're right, politics can and will hold us back, but not entirely.
Now if you want to see me foam at the mouth, we can talk about the genetics and politics of pain management and how, if only pigs could fly and asshats didn't run the government, people like Richard Paey could be exonerated on the basis of their genes.
We are *thisclose* to having a test panel that would show which patients actually NEED those massive doses of opiates, which ones are going to become dependent... we can prove that dependency and addiction are categorically separate. It just kills me to know that the Karen Tandy's of the world will ignore and discount these facts, no matter how hard the evidence.
As soon as we've got the pain management test up and running, I'm going to put out a call for people to hook me up with Richard Paey and other patients and physicians who've been persecuted by the FDA.
