Transcript: Oxcarbazepine Use, Choosing an Atypical Antipsychotic in Bipolar Treatment

Dr Gregory Mattingly:

"So let's dive into some of the common questions we've had here today. The first question we had, and I think it's a great clinical question [because] it's something we all struggle with every day, is how do you decide between different atypicals for a patient who's never been on an atypical before?

So if this is someone who comes new to your office, they're 22 years old, they're 35 years old, they're struggling with bipolar disorder, but they've never been on an atypical, how do you pick and choose?

Let me start by thinking about the phase of the illness they're in. We have certain atypicals that are very approved for bipolar mania, but they have limited data for bipolar depression. And having been an investigator in many of those trials, many of the medicines that work for bipolar mania have failed in bipolar depression. Think about which phase of the illness they're in.

If somebody's in a pure manic phase, use one of those medicines that does have a bipolar manic indication. Remember that as people come out of that manic episode, you may need to change the medicine you're taking. Quite often during a very manic episode, we'll use them more sedating, atypical antipsychotic, olanzapine, quetiapine. But remember at first, sedation can be your friend in mania, but long-term sedation winds up being your enemy. So, trying to transition people off of those medicines that have a high sedating burden as they go through the transitions.

Where it gets a little trickier, where we have less options is when we get to bipolar depression and bipolar with mixed symptoms. There, we have a much smaller list of atypicals. And remember, the ones that don't have indications, many of them have tried to get indications and they failed. They just did not work consistently for patients. They may have worked for one patient here and there, but they didn't consistently move the needle.

We have 5 atypicals that are approved for bipolar depression. If someone's having depression, I think that's where your money is, that's where you're going to go. Now, among those 5 atypicals, I've done studies with each of the 5, we know they're significantly different metabolic risk factors. I tend to start with one of the ones that has a lower metabolic risk, less weight gain, less risk of type 2 diabetes, and those would be the ones I would typically start with if somebody came in with bipolar depression within my practice. I think that narrows our realm down to lumateperone, lurasidone, and cariprazine would be the 3 that in general, I think have a lower metabolic burden out of those 5.

Once again, remember the dose that you use may slide up and down. The perfect example would be cariprazine. At a low dose, very effective for bipolar depression. As someone goes into mixed symptoms, you may want to slide that dose. You may want to slide the dose up to capture the patient as they go into a mixed episode. Slide them up to three milligrams, and if they start cycling into more of a manic episode, the brain's more hot for dopamine, I need more medicine in the system to pull tone down, then slide that dose up to three to six milligrams. So in my clinical practice, it's not uncommon that my maintenance dose for one of those during a depressed phase may be a little bit lower. And as someone starts cycling, I'll slide the dose up, I'll capture them, and then I'll pull that dose back down.

So, my clinical tips and tricks would be think about the phase of the illness somebody's in. If it's mania, think about the ones that have anti-manic indications. If it's depression or depression with mixed symptoms, think about the 5 that have bipolar depression indications. Then, think about the metabolic burden of each of those, trying to use ones that are more metabolically friendly whenever possible. And if you have started with the medicine, that's highly sedating because somebody's agitated, try to decrease that sedation load as they start improving.

The next question dives outside of the world of atypicals. How about the world of carbamazepine and oxcarbazepine? And so we have 2 different people that submitted questions here. First of all, is there a place for oxcarbazepine in the treatment of bipolar disorder? So I would rank oxcarbazepine, it's probably like a step 3-level medicine. It's a medicine that does have some open-label data. It's a medicine we probably all use clinically on and off within our practice for people that have bipolarity or bipolar spectrum illness. But, it does not have an FDA indication for bipolar disorder.

With oxcarbazepine, I think we think about, okay, it's a place where off-label, I may use it, maybe a little gentler, maybe a little friendlier than some of the other versions of carbamazepine. But you like to stick with medicines that have indications. Long-acting carbamazepine does have indications for bipolar prevention. It's not a treatment for acute mania, it's not a treatment for acute depression. But it does have data about prevention of cycling, which is where the other mood-stabilizing anti-epileptics tend to have indications as well. I would lump it in that group with valproate, with lamotrigine. Those are medicines that they take a while to get into your system. So they have not been shown to work for acute bipolar depression. They probably take too long to take an effect. Their indication is for the prevention of cycling, so relapse prevention.

A couple of warnings that I would give you about each of those with valproate, valproate, there was a large study that just came out of Europe. It was the largest study to date, it came out of the Nordic countries, where they looked at women who had gotten pregnant while taking any of the anti-epileptic medicines. Some of those women were taking it for seizure control, and some of them were taking it for bipolar and mood prevention.

[Researchers] looked at developmental disabilities in the offspring over the next handful of years. By far and away of all of the mood stabilizing anti-epileptics, the one that had the biggest developmental burden on the young offspring, higher rates of autism, higher rates of developmental disabilities, higher rates of neurocognitive issues was valproate. Valproate was head and shoulders above all of the other medicines in that anti-epileptic class that we use for mood stabilization. I think a take home there is during pregnancy, valproate, that's kind of a no-no. We stay away from valproate during pregnancy, and that's what most of our guidelines tell us there.

The second medicine that would be an off-label treatment for it, but it's a treatment we do use in psychiatry that actually showed the next biggest burden for developmental risk was topiramate. Topiramate during pregnancy, I would say valproate, a definite no-no. Topiramate, this data looked not very reassuring there. All of the rest came in at about the same level of risk, slightly higher than baseline, but not significant as far as having to say an absolute contraindication. I would place our other mood-stabilizing anti-epileptics in that category.

One of the things I would keep in mind always when using carbamazepine, which was one of the questions, remember, carbamazepine speeds up metabolism of everything. It speeds up metabolism itself, so it auto induces and drops its own blood levels. It'll speed up metabolism of many of our psychotropic medications. And here in St. Louis, I have a good colleague who unfortunately, had a negative outcome where he had a young woman who got pregnant while taking carbamazepine and he forgot to warn her that it would speed up metabolism of birth control pills. I don't tend to use the carbamazepine molecule in women of childbearing years, who are using oral contraceptives.