Transcript
As I alluded to before, occasionally, there are patients who don’t take medicines in the way you prescribe them. Of course, this doesn’t happen to my patients. It’s always someone else’s patients. But that being said, we’re often very poor judges of who is actually taking their medications even when you put people in clinical trials.
So this is a schizophrenia patient who knows that here she is in a study. And often, they do these studies with what’s called a MEMS cap. MEMS cap is a cap which has an electronic chip embedded in it. Every time the person opens the pill bottle, it registers the date and the time. It’s a good proxy for adherence. The assumption is if they’re going through the trouble of opening the pill bottle, maybe they’ll actually be taking their pill.
Even when you have people on a study and you say we’re going to consider you adherent if you take your medicines five days out of seven which is about 70%, the actual level of adherence was about 43%. Meaning 57% of people were nonadherent even though they’re on a study and even though they’re being watched.
But of course, if you ask the patient well what proportion of you are actually taking your medicines five days out of seven, 95% said they were adherent. And if you ask the psychiatrist, their estimate of adherence was 93%. And so we often have no idea what actually is going on with the patient. We often assume that the person is taking their medication simply because they show up to their appointments and they refill their prescriptions And the fact that they remained stable just has to do with biological features of their illness. With whatever level of adherence or whatever level of drug exposure they are experiencing, it keeps them together.
So for example, you have somebody on 20 mg at bedtime of aripiprazole. Typically, we get these as 12-hour troughs and you order it. So what result would you expect? Well, I would expect something in the middle range of 200 ng/mL. And so, here we see a mean level of around 230 with a large standard deviation. Again, you have to account for variations there. But certainly if somebody was on 20 mg a day of aripiprazole and their level was 20, you know they’re not taking their medication.
For haloperidol, a good relationship to remember is that 10 mg per day, again given at bedtime, so 10 mg qhs should generate a trough plasma level of around 7.8 ng/mL. We have a few other ones as well here.
For olanzapine, the data are much more solid. You can see for a nonsmoker, your plasma level is about two times your oral dose. So if you had somebody on 10 mg qhs, you would expect a trough plasma level of 20. On the other hand, if they are a smoker, you could see the relationship is diminished somewhat.
And so there are a number of drugs which both inhibit and induce this. You can see it actually has a significant interaction with strong 3A4 inhibitors which increase the area under the curve ninefold. And you cannot use it with strong inhibitors.
You can use it with moderate inhibitors where it increases it only twofold.
Conversely, strong inducers reduce the plasma levels by 80% and you’re just wasting your time if you try to combine lurasidone with let’s say carbamazepine or phenytoin. There’s also a food effect as well.
Then I say we’ve published data on people who tolerate levels up to 30 and there are people who tolerate even higher levels. So the best way to use laboratory ranges for antipsychotics is to look at the lowest number, meaning the threshold for response. That is probably pretty good data. The upper numbers are usually based on just some idiosyncratic reading of the literature.
What should I do?
The most important thing is to document that the patient is tolerating this particular level and then recheck it. Occasionally, there are lab errors. But if it comes back 1000 again on a repeated basis, you can say, all right, this is what this person needs to be stable and they’re showing no adverse effects.
But rapid reduction of doses is most likely going to destabilize your patient and more likely than not the patient may need that level for response.
References
- Byerly M, et al. Psychiatric Services 2007; 58:844–847.
- McCutcheon R, et al. Antipsychotic plasma levels in the assessment of poor treatment response in schizophrenia . Acta Psychiatrica Scandinavica 2018; 137:39-46.
- Meyer JM, et al. Psych Clin N Am 2016; 39(4):541-556.
- Potkin SG, et al. CNS Spectrums 2013
- Potkin SG, et al. D2 receptor occupancy following lurasidone treatment in patients with schizophrenia or schizoaffective disorder . CNS Spectrums 2014; 19(2):176-81.
- Meyer JM. Current Psychiatry. 2015; 14(11): 16:19-20 2.
- Eap CB, et al. J Clin Psychopharmacol 2004; 24(2):214-9.
- Remington G, et al. J Clin Psychopharmacol 2013; 33(2): 161-162
- Midha KK, et al. J Psychiatr Neurosci 1994; 19(4): 254-264.
