Comparing VMAT-2 Inhibitor Options for Tardive Dyskinesia Treatment

Amber Hoberg, MSN, APRN, PMHNP-BC, discusses the key clinical differences between the 2 FDA-approved treatment options for tardive dyskinesia: deutetrabenazine and valbenazine. Nurse Hoberg provides details on their mechanisms of action, contraindications, and side effects—all important considerations when helping patients find the best medication option for their treatment.

For more expert insights on the disorder, visit the Tardive Dyskinesia Excellence Forum.

Read the Transcript

Amber Hoberg, MSN, APRN, PMHNP-BC: Hi, I'm Amber Hoberg. I'm a psychiatric mental health nurse practitioner in San Antonio, Texas. I have my practice, Morningstar Family Medicine, as well as I work for the Baptist Health System.

Psych Congress Network: What are the practical differences between the novel VMAT-2 inhibitors approved for tardive dyskinesia treatment? How can healthcare providers choose the most suitable therapy or individual patients based on these differences?

Nurse Hoberg: Let's talk about the two VMAT-2 inhibitor options that we have. First disclaimer is that there are no head-to-head trials comparing the two VMAT-2 inhibitors together showing one to be superior over the others. So what I'm going to actually talk about is just some of the key differences between the 2 medications.

With deutetrabenazine, you do have the twice a day dosing option as well as now you have a new formulation of deutetrabenazine, called deutetrabenazine XR, which is a once a day formulation that you can give to your patients. One of the key differences is that deutetrabenazine goes down the CYP2D6 system. If you have patients that are on strong CYP2D6 inhibitors like fluoxetine or paroxetine or bupropion, you can still use deutetrabenazine--you just can't go over the 36 milligram daily option. Also, if your patients are poor metabolizers of this pathway, again, you can use the medication, you just can't go over the 36 milligram dosing. Deutetrabenazine is not metabolized down the 3A4/5 system.

Valbenazine, on the other hand, is metabolized both by CYP2D6 and the 3A4/5 pathway. That's one thing to be mindful of is when you are looking at patients' medications, they're not just on VMAT-2 inhibitors, they're on other medications as well. So you do have to know how those medications are metabolized so that you can make the best choice for the patient. With valbenazine, if you have patients that are on strong CYP2D6 inhibitors or they're poor metabolizers at the pathway, you can't be on more than 40 milligrams of valbenazine. If they're on CYP2D6 inhibitors, you can still use valbenazine again, not being able to go over 40 milligram dosing. But if your patient is on inducers, then it's really not recommended to use this medication with those particular types of medications. The goal of treatment is always to maximize dosing, to be able to improve patient's functioning as well as improve patient's movements. So whatever VMAT-2 inhibitor you can do that with, that's where I would start.

Also, when it comes to just the isomer profile, both of them are very different. Valbenazine, when you look at its isomer, it's only got the plus alpha isomer. So, when you actually look at its binding affinity, it only binds to that plus alpha. It doesn't bind to any other off-target receptors, whereas deutetrabenazine binds to all 4 isomers: plus alpha, plus beta, minus alpha, minus beta, and it also has some off-target receptor activity. It really depends on what you're looking for there as well.

One of the other key differences is valbenazine comes in a capsule formulation and there actually have been studies done where you can actually open valbenazine capsules and sprinkle it on food or in drinks to be able to administer to those patients that can't swallow or maybe on PEG tube feedings, whereas deutetrabenazine cannot be crushed or chewed.

Also, contraindications are a little bit different. If you're using deutetrabenazine for tardive dyskinesia, they can't have liver impairment, it's actually contraindicated for any kind of liver impairment for those particular patients. Also, if they're on reserpine, it's a 20-day washout off of that medication before they could start deutetrabenazine as well as MAOIs. It's 14 days off of MAOIs before you could actually initiate deutetrabenazine. Whereas with valbenazine, its only contraindication is if they have an allergic reaction to that medication or any of its active components, then you wouldn't want to give that to the patient. But they actually do have data that specifies that if your patient has moderate or severe hepatic impairment, you can still use 40 milligram dosing of valbenazine as well as renal impairment. Valbenazine is not metabolized on the renal pathway. So you can use all 3 dosing strengths to be able to treat your patients with tardive dyskinesia.

Let's talk about one last key difference between the 2 VMAT-2 inhibitors, which is their side effect profile. Deutetrabenazine in the TD trials, they actually only had 2 that separated out from placebo, which was nasopharyngitis and insomnia. In valbenazine, when it comes to their side effect profile, what separated from placebo was somnolence, anticholinergic effect, balance disorder, falls, headaches, akathisia or what we call restlessness, vomiting, nausea, and arthralgia, are the ones that separated out from placebo in this particular medication. So that's another key difference to keep in mind when you're talking to your patients to try to determine what VMAT-2 inhibitor to use.

Amber Hoberg, MSN, APRN, PMHNP-BC, is a board-certified psychiatric mental health nurse practitioner from University of Texas Health Science Center San Antonio. She has been working for the past 12 years with the adult and geriatric populations, treating all types of psychiatric conditions. Her background, as a Psychiatric Advanced Practice Nurse, includes outpatient, inpatient, group home, and nursing home/ALF settings. She currently works for Baptist Health System and Morning Star Family Medicine PLLC treating the chronically mentally ill in both inpatient and outpatient settings.