The CYP2D6 gene...Read this one!!! Seriously. It could mean all the difference!

Okay, for all you folks on antidepressant meds, prick up your ears! CYP2D6 is a gene. In short: it regulates how neuroleptic (sp?) meds are communicating and traveling to the brain...my definition may be a little sophomoric, but here's the short and the long: Have it tested. If you are on ANY type of antidepressant, have it tested. If you are considering going on antidepressants, have it tested. I'll say it once more: have it tested. I was/am med-resistant...to EVERYTHING. Oh, the side-effects were there, but no discernable dent had been made in my depression (misdiagnosed as bi-polar type 2; which is beside the point here). And I had no idea why, and the medical professionals could offer no answers...Until the day I heard that odd string of letters and numbers: CYP2D6.

CYP2D6…here's the skinny made simple [with a little help from my wife who is a Biochemical Geneticist, and the one who figured this out…with no help from my doctor, I might add]: the CYP2D6 gene has two alleles, like two little hands that send medication to the brain. If one of the “hands” is malfunctioning (as is one of mine), then you are considered an "intermediate metabolizer." This can have serious repercussions...first, there isn't enough medication getting to your brain. Most of the time, a patient will simply report this as, "The drug isn't working." So the doctor will increase the dosage. Bad news. Here's why: you can have a serious backup of the medication in your bloodstream or liver, leading to harsh interactions with other meds, higher instances of negative side-effects, and, in my case, a near-lethal prescription dose (can you say four day coma? I couldn't...I was in a coma).

What makes increasing the dosage even worse (insult to injury, more salt in the wound) is the drug STILL won't get to your brain. The hose (the remaining, functioning allele) simply isn't large enough to let enough medication through. Again, I'm shying away from clinical descriptions of how this all works on a genetics or neural-chemical level because it's really dull to read (so don't flame me). For me (and I admit I'm probably an extreme example), the result was four years on EVERY class of drug (SSRIs, MAOIs, tricyclics...and even talk of ECT!!!), and nothing to show for it but six suicide attempts. Also, I was led down that circular pharmaceutical path where you take one drug, have side effects, so another drug is prescribed to take care of that, but then there are new side effects, and yet another drug is prescribed to take care of those! It was an endless spiral, and, at the height of it, I was taking 6 different meds at once, several times a day!!!...Each one trying to dampen the undesirable effects of the last. Nightmarish doesn't even begin to describe it.

Sooooooo, eight months ago (after being genotyped and diagnosed as an "intermediate metabolizer"), I made the decision (under doctor's care and supervision--VERY IMPORTANT) to stop all of my meds (except xanax, for anxiety, which works differently from the other meds). I suffered the worst withdrawals imaginable. Several abstracts I've read on PubMed have likened antidepressant withdrawal on par with that of heroin or cocaine. Fun. But I'm here to tell you, I'm better for stopping the meds. The drugged "haze" has lifted. My energy is SLOWLY returning. And people around me have been saying more and more, "You seem like the old you." Which they mean as a good thing. I'm even going back to work (interviewed last week...now I have to make my decision of where). That's not to say that my depression isn't still with me. It is. It's like a shadow. But without all the crappy side-effects and other problems the medications were causing, it feels more manageable (at least during the day...nighttime is a different chapter altogether).

So, back to CYP2D6. There is a very good chance that your doctor isn't even aware of this kind of genotyping, of CYP2D6 (called "sip"2d6, for short), or there's even a test available. There is a lot of literature going around right now about this...check it out on the web. www.PubMed.gov is a good place to start (try a search like "cyp2d6 and antidepressants" and see what comes up). The major consensus is: anyone who is (or is considering) taking antidepressants, should have this test done. It will give your doctor a better idea of a base starting point (how MUCH medication you should have), or if you should even try antidepressants at all. Here is a quote from one of the studies: "The therapeutic drug monitoring and the genotyping findings resulted in recommendations to physicians to alter the medication strategy of 146 (64%) patients." The doctors altered the medication strategy of over HALF the patients in the study after they were genotyped. Simply, they needed an adjustment to their dosage. Pretty important information, I think.

(Here's the link to that abstract: http://www.ncbi.nlm.nih.gov/entrez/query.fcgidb=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17050797&query_hl=4&itool=pubmed_docsum)

Getting tested is simple (nothing exotic), just a blood test, and with a prescription should be covered by insurance. For my part, my body has this little malfunction, and it won't allow me the luxury (if it can be called that) of benefiting from antidepressant medication. It was a long road that felt straight and steeply inclined, but (turns out) it was only a frustrating circle. So, if you're in early stages of antidepressants, get the test. If you seem resistant to the meds, as I was, this test is VERY important. It was the silver-bullet that told me the most important piece of information: why. And if you've been on meds a long time and they seem to be working, you may not think you need this...but, then again, it's never a bad idea to have all the facts. Again, it's a simple blood test. You can have it done the next time you go in to have your blood levels checked. Also, I don't want any of this to sound alarmist. My case was peculiar and harsh...but not all are. The important thing I'm trying to express to you is this: you may not be getting the right thereputic dose of medication you need to help your illness...or, in my case, your medication may be causing you to get worse. Being genotyped can be a huge leap in understanding how your body is dealing with the meds.

And, of UTMOST importance, if your doctor does not know about this test, demand he/she find out. Don't ask, don't gently urge, DEMAND IT!!! They're YOUR doctor. This is YOUR treatment. You have the RIGHT to know all the facts, and you have the right to ask ANY question. I cannot stress this enough. Your doctor is just a doctor...just a person with a job (and a huge student loan). He/she may not be up on the latest literature (although, they should be). And if you're not getting the right type of feedback, the right kind of give-take, then find another doctor. You are allowed to fire them (in fact, say that. Say, "Doc, you're fired." It feels pretty good). You are allowed to go elsewhere for treatment. That's what I had to do.

So...good luck, out there. I hope this helps and enlightens. My thoughts are with each of you...every day.

-Steven

Post Edited (thirdmonster) : 11/1/2006 12:06:57 PM (GMT-7)

Good question...it's a tough battle now. I still go to therapy, although that seems to be like chasing cars (somewhat pointless). And I have setbacks, like this past weekend, when my emotional burdens are simply crippling. Xanax will sometimes "talk me down," calm my nerves, although I try and keep the dependency in check (xanax is horribly addictive) and only take when I absolutely have to...as a side note: my wife helps with this by being my dispensary. She is my check/balance system. I suggest this to all others who fear dependencies of their medications (if you don't have a significant other to help, but see a therapist each week, you can easily entrust them to dispense only enough for one week at a time). But if I'm having an off day, I try and get my mind on something else. The iPod is my new best friend. Audiobooks rock! But even there, I have to watch out for what I'm listening to...play the wrong song, trigger a painful memory, and your whole day can spiral out of control.

I think going back to work will help. Heck, just putting my resume together bumped me up a level, made me feel like part of the "real world" again. I'm a visual effects artist and (aside from the artistic aspect) it's a lot of problem solving...keeps my mind busy. Sometimes I feel the most damaging part of the last four years was staying home, or in the hospital, with nothing but time to stew inside my own head. So, back to work with me. But that leaves nighttime: the most difficult piece of the day, right when I'm trying to fall asleep. Not sure what to do there. Ambien is available, but, again, can only be used for a finite period of time, and is also addictive. I'm still trying to puzzle it together, I guess. This is my new great experiment...living a "normal life" with depression as my shadow, without a pharmaceutical safety net (which I suspect is sometimes a crutch). And I'm frightened. Very frightened. There are so many new unknowns to deal with now. But I'll keep posting here. We'll see. Maybe I should start a new thread, day by day, week by week accounts of what's going on, how I'm dealing. Maybe...

-Steven

P.S. You know what this site needs? Blogs!

P.P.S. And monkeys. Lots of monkeys!

Post Edited (thirdmonster) : 10/31/2006 2:51:54 PM (GMT-7)

Thanks for saying hello and welcoming me into the fold. Yes, the genetics portion of treatment is something new (well, within the past five or so years). But I'm glad it's happening. Understanding the mechanics of how a medication is working in your body is going to be (I think) an important advance in treatment. And I hope I didn't give the impression that my case is somehow typical, and everyone should be suspicious of meds or their docs. I'm certainly not saying you should act as your own doctor and come up with your own treatment. No. Not by any stretch should this be done. But being armed with information and taking an active roll in your treatment is always a good thing.

As you pointed out, everyone is different. And that's my point about getting genotyped...it will give your doctor (a psychiatrist) a better understanding of how the medication will work, or is working, inside ***your*** body. Up 'til now, that has been determined by either how you're feeling (which is always subjective), how you're acting (an outside, objective opinion), or by the numbers in your blood work. But blood work can be misleading, since it can look like you have the therapeutic dose in your bloodstream, but your body may not be metabolizing it correctly. Again, being genotyped will help assess this. And going to a primary care doc, as you've said, should only be used in extreme cases. They are not the experts on this sort of thing. I only mention them because if you're out there for the first time looking for help, they may be the only people available on short notice...many psychiatric doctors (at least in Los Angeles) have lengthy wait-times before your first visit. And, often, insurance companies require you to be seen by primary care before you can see a psychiatrist. But (here's a good tip) you can have your regular doctor order specific tests in advance of seeing a psychiatric professional. Things like thyroid, hormones, CYP2D6, etc. Those types of test can help you rule out physiological factors that may be altering your mood...and you can have those tests back and ready when you do get to see your psychiatrist for the first time. And your regular doc may decide to put you on a low dose of antidepressant to help you get through the waiting period.

I have to say, though, that I feel very lucky to have had a plethora of information at my fingertips. My wife is a lab director, an expert geneticist, and she works with a lot of other doctors and experts whom were like an encyclopedia. It was like having an M.D./PhD. dream-team working on my case. And we're still working on it, trying to find other routes to the brain, help bump my mood and energy levels up...but this is still under the supervision of a psychiatrist. I will stress that point. He is not secondary. Anyway, I've rambled on too long now, so I'll sign off.

Take care everyone.

-Steven

Click on his name at the left side of the post. It will take you to his profile. He may have an email address there. That would be the best I would know...