Getting the goods on titration

August 23, 2007 2:58 AM

When I see the word "titration," I think of pipettes, bunsen burners, and that stoner dude in high school chem class. Why is "titration" so ubiquitous in online discussions about certain kinds of meds these days? What's the best way of coming up with an effective titration schedule for a med?

I've recently started on a new course of migraine meds, and the online materials for my medicine--topamax--recommend "titrating" to a particular level. Color me confused!

First, what's all of this business about titrating, anyway? Is it necessary to avoid the tolerance effect that sets in with certain types of meds? Or is there another scientific principle involved? Also, why does it appear that there's much more attention on titrating in online literature now than, say, a few years back? Am I imagining things?

Second, when it comes to meds, I'm old school. I'd prefer to take whatever dose works. If 25 mgs once a day works (as it does right now), fine. I'm cool! Leave it alone! No need to screw around! That's my current way of thinking.

Should I dump this way of thinking, and follow a more disciplined titration schedule? If so, what's the best way of formulating one? I know I can get a titration schedule from a neurologist or online, but I think it might be better to customize titration to fit the day-to-day results I'm getting from the meds. What's your take on this?

I know you're not a doc or my doc, and that I should be consulting with docs and specialists. Please send me your thoughts and experiences and advice.

posted by Gordion Knott to health & fitness (6 comments total)

If you don't want to talk to a physician, you can talk to a pharmacist. Not only will you get better advice than from random people off the internet, but it will be free!
posted by grouse at 3:56 AM on August 23, 2007

Firstly, "titrating" has been a long standing medical practice with respect to medication dosing so I think you may well be imagining things. That said, with many of the newer agents that have neuropsychiatric effects, titrating would seem ever more important (though we've been doing it with blood pressure medications for decades).

Generally speaking if a dose of something works (and one has to define 'works' depending on the circumstances of course), I'm not sure why any physician would want to continue increasing the dose. Most folks aim for the lowest effective dose of anything. That said, consider the use of a medication to prevent against seizures. A patient may think it 'works' at a low dose because they happen not to have a seizure for a few weeks at that dose, but past experience may suggest that in the long-term a certain higher goal dose is much more effective, and the short sampling time in this case may cause a bias on the part of the patient. Again one has to consider the paticular circumstances. In your case, I'm going to guess that the medical literature on migraine prophylaxis probably suggests a certain typical dose for effective treatment with Topamax in most patients. But as migraines aren't necessarily life threatening, it would seem reasonable to take a more conservative approach and essentially see how you do at lower doses before blindly increasing the dose. If I'm not mistaken, they've compared dosages in studies and found that at 50mg there is some modest reduction in migraines relative to placebo, but this was not statistically significant. More robust results which were also statistically significant were noted at 100mg with minimal additional benefit going up to 200mg. But these are studies of large groups of people, so on a person-to-person basis there will be some variation in what dose works. The best thing to do is talk to doctor and see what their reasoning is.

The most common reason medications are titrated is probably related to their side effects. In many cases for example, medications may be oversedating or upset the stomach with initial use at a higher dose (I suspect this is probably the case with Topamax, though I'm not a neurologist), but with time patients habituate to these side effects when the dose is slowly titrated.

Here is one example of the medical literature that has prompted such titration schedules for Topamax in the setting of seizure prevention. A good bit of info can also be found here, particularly under the heading of "Migraine."

Personally I think it'd be reasonable to go slow on titrating the dosage if you're noticing dramatic benefits already at a lower dosage. With migraines, you are the best judge of if something is working or not -- the data from studies should only serve as a rough guide. Also, I'd recommend keeping good track of your migraines with a log book so you can really get a sense of how things are going.
posted by drpynchon at 4:07 AM on August 23, 2007

Drpynchon has a good answer; I just want to add that another variable to consider when titrating drugs is how long it takes to reach a steady state concentration in the blood; I won't go into a detailed pharmacokinetic explanation unless you ask me to, but for topamax it takes 4-5 days, which means that you should wait at least that long between changing doses when assessing side effects, clinical efficiency, and so on. This agrees well with the standard regimen of changing the dose in weekly increments until the desired dose is reached.

I also second grouse's advice to ask a pharmacist as well as your doctor about this.
posted by TedW at 5:25 AM on August 23, 2007

I don't know about titrating exactly, but I have been on topamax. You have to "build up" to your dosage slowly to avoid the worst of the side effects. This way, your body has a chance to sort of get used to the drug in your system. Topamax has some serious nasty side effects (google or search here, i know there are a couple threads) and trust me, you don't want to go head on into them. Feeling stupid (it's nickname is 'dopamax'), pins and needles, everything tasting like crap, and serious anxiety are the 'minor' effects i can think off hand. Kidney stones and glaucoma are on the more serious side. Obviously, everybody reacts differently. But if it works (i'm assuming your taking it to control migraines?), it really works, and it's worth the trouble.

Didn't your prescribing doctor give you a "titration schedule"? I know when I was on it, I was to spend 5 weeks building up from 25 to 100 mg a day (but i never got that far, due to that fact my eyes started to hurt, and my neuro wasn't taking any chances., given the whole glaucoma thing.)
posted by cgg at 7:30 AM on August 23, 2007

This usage of the word "titrating" annoys me, because it is not even proper jargon - it's just co-opting of a chemistry word and leaving its meaning behind.

It means adjusting the dosage until the desired effect is achieved, nothing else. There's no magic about it, although it is useful to be able to understand the drug's kinetics (half-life, interactions, etc) while doing it.

Some medications induce their own metabolism. That means that the liver, over a period of a couple of weeks, responds to the presence of the medicine by increasing its ability to dispose of the medicine. That means that 25 mg in week 1 is not equivalent to 25 mg in week 4. I find that, despite careful explanation, only maybe 10% of patients are able to comprehend this phenomenon, so I rarely bother to explain it any more.
posted by ikkyu2 at 8:01 AM on August 23, 2007

. . . but you still give them titration schedules, right ikk? When changing meds to control a serious condition it may be necessary to "tail off" the med you know works and "phase in" the one you're less sure about. For example, some seizure meds (in particular some I take) have a truly hideous side effect that occurs in a small portion of the population. It has been found that if you raise the dosage slowly you are less likely to see that side effect. Ikkyu2 probably knows why that is; I don't know why and I don't care, but I sure as hell don't want the rash of death, so I do what my doc says.

Also you have to tail of the other medication slowly, so if the new med is less effective you don't suddenly have the patient (me) flopping around like a fish in the middle of the subway. That process (which for me took months) was called titration by my physician. I never questioned it.
posted by The Bellman at 9:37 AM on August 23, 2007