Drugology (part 2)

The other drugology fact that seems to be entirely absent from general medical awareness is, I think, a serious oversight. I don't take Ritalin, myself, but I do take medication every day to treat my ADD, and none of the four or five medical professionals involved with my medication over the years ever came close to getting the dosing schedule right. This same issue is relevant to just about anybody who takes some kind of medication on a daily basis, especially if, like me, you don't want it to be doing its thing 24/7. I'm going to go back to methylphenidate for my example of the Big Mistake that appears to be endemic to the medical community.

While every individual is, well, individual, kids and adults treated for ADD and taking Ritalin often have similar time tables for medication. Take one tablet in the morning (say, around 8am), and a second one around noon. Adults in particular might take a third one at around 4, and possibly a fourth one around 8pm, although usually we want the effects to start wearing off before bedtime. A pretty common dose would be a 10mg tablet.

The problem is, this schedule completely fails to include "blood serum half-life," the rate at which a drug is cleared from your bloodstream by your liver and kidneys. At noon, there's not enough methylphenidate left to have the desired effect, but that doesn't mean that it's suddenly gone from your system. There's a lot left, just not enough to get the job done. Taking another full dose means, well, let me draw you a picture...

The scale is rather arbitrary, since it's hard to relate how much medicine goes down your throat with how much ends up in the bloodstream. But let's say that "5" is the amount required to produce the desired effect. Sure enough, the total medicine is dropping below 5 right around noon. Time for another pill. Add the red line to the blue and you get, gosh, way too much!

Nevertheless, it is still dropping below the effective point shortly before dinner, so a grownup who needs to stay focused and productive through dinner time (and get those bills paid afterwards) might well take one more around 4pm. See Chart 2.

Good grief. During dinner, our archetypical person has twice the amount of methylphenidate required to be effective in their bloodstream. Now, like most stimulants, methylphenidate is actually extremely safe. Aspirin could only wish it were as harmless as Ritalin. (You might think Adderall is an exception, since that's the brand-name for prescription methamphetamine. However, keep in mind that somebody "on speed" will usually administer a dose of meth about equivalent to an entire month's worth of prescription Adderall.)

Safe or not, dumping needlessly huge amounts of medication on your liver and kidneys just doesn't make good medical sense. Also, this same overdosing curve applies to any daily drug. High blood pressure meds, allergy pills, depression, and so on, and many (most!) of those medications are not as safe as methylphenidate.

Did the doctor just push the schedule too close together? Nope, spreading out the doses doesn't work. See chart 3. Now there are big holes in the middle of the day where the medication level is too low to be effective. And the level is too high late at night to be able to fall asleep easily.

The answer, once you draw out the blood serum levels on a graph, should be f****ng obvious. Don't take full doses in the middle of the day! Ritalin comes in 20mg, 10mg and five milligram tablets. So let's just try taking a half dose at noon and in the afternoon, shall we?

Why, yes, that is a huge improvement! You can see the red and yellow lines, representing the individual doses contribution to the overall medicine level, are half the size of the morning dose. Overall levels of medication in the bloodstream are enormously more stable and even. Yes, there's a problem gap between around 3 and 5 pm. That's an easy fix. Let's just move the afternoon dose up about 45 minutes, to 3:15.

So compare Chart 5 to Charts 1 and 2. With the 10/5/5 dose, we're getting a far more even level of medication and taking only 2/3rds as many milligrams as before. It's true that the meds drop out on chart five right around dinner time, whereas on chart 2 they were good until 9 at night. That's an easy fix: five milligrams at 5:30 extend the effective range until about 9:30. Even better would be four milligrams at six, but you can't get Ritalin in 4mg tablets.

A few years ago, I did, in fact, try to get a prescription filled so that I could actually take the right amount of medicine at the right time. "I'm sorry, but two different sizes of pill are considered two different prescriptions, and won't be covered by your insurance." Yes, insurance companies are well known for being institutions of poop-headed-ness. Fortunately, as with my example here, the solution was to have the prescription written for four 5mg tablets per day, and I just took two of them in the morning.

It's really stupid that the insurance companies don't grok the idea that maybe I need the same medicine at different dosages during the day, but it's still just one condition and one prescription. But then again, obviously doctors aren't ever prescribing serum-aware medication, so there's not really any reason for the insurance companies to bother changing.

I spent quite a few years trying to figure out when was the best time to take an afternoon dose of my medication before it finally occurred to me that my problem was not "when," but "how much." Being aware of this issue has made a very serious change for the better in my life, and I cannot believe that it isn't vitally important to uncountable thousands of other people on chronic medication. And yet, I have never had any doctor suggest taking half a tablet or some reduced amount during the day, nor have I found any general awareness of this on line.

Is it really just too complicated to bother with? It is complicated. I didn't just construct those serum level curves out of wishful thinking. The key numbers are "time to peak" (how long after swallowing the tablet does the amount in the bloodstream reach its highest point) and the aforementioned blood serum half life. Methylphenidate is particularly uneven, with a time to peak (in children) that ranges from 20 minutes to two hours. I found conflicting opinions on the half-life; one source said "two hours," and another one said "three." Neither one provided a reference, alas. So these graphs are based on researched averages, but any particular individual might have a significantly different response, and thus require a different dosing schedule. The medication I currently take typically has a peak serum time of around 120 minutes, but it's closer to 150 for me. (I haven't actually had blood tests done every 30 minutes for a few hours after taking it, so I don't really know for sure; I'm guessing based upon my response to it.)

I did happen to turn up some interesting evidence that this mis-dosing isn't just in my imagination. There was a study done in 1999 comparing Ritalin and Adderall in treating ADD in kids. As part of the conclusion, the authors said (emphasis is mine) "Time-course results indicated that the afternoon dose of medication seemed to have a larger effect than the morning dose, raising the possibility that afternoon doses of stimulant medication may be able to be reduced relative to the morning dose without a corresponding reduction in efficacy. This practice . . . is almost never used in empirical investigations and no studies have systematically investigated the practice. Our results suggest that systematic studies of a reduced midday dose are indicated."

They almost sound surprised, as if the very idea that some of the first dose is still in the blood stream hadn't even occurred to them. If so, it wouldn't be the first time that some particular idea was totally obvious to me, and completely invisible to everybody around me. But this seems so obvious, so completely non-mysterious, that I'm left scratching my head. It's not rocket science! It's adding one plus one and getting two! Or maybe it's adding 12mg and 18mg, but it's still just basic arithmetic.

It's generally not too hard to find out the half-life of a drug, if you know you're looking for the information. Quite often, it's just listed in the side bar on Wikipedia. Wellbutrin, for example, has a half-life between 22 and 30 hours! That means if you take it once a day, it will be at least five days before the amount in your bloodstream levels out, and it'll be about 25% lower in the evening than it is in the morning after you take it. Zoloft has a 26 hour half life. Prozac is especially tricky. Regular use causes it to inhibit its own metabolism, so the half-life starts at around 2 days, but becomes 4-6 with ongoing use. Modafinil has a half-life of 12-15 hours, and, according to Wikipedia, is sometimes prescribes in two doses, one in the morning and one at midday. I rather doubt that patients are being advised to make the midday dose only 50mg, while taking 100mg in the morning. If not, then, as illustrated, the afternoon dose is causing a needlessly huge spike.

If you, Dear Reader, are taking some regular medication, please feel free to print out this essay, or perhaps just some of the charts, and discuss this with your doctor the next time you see them. I would be most interested to learn of the results.