The FDA approved the 2 VMAT-2 drugs for the treatment of tardive dyskinesia in 2017.
The use of US Food and Drug Administration (FDA)-approved valbenazine and deutetrabenazine for tardive dyskinesia treatment can be valuable for patients with moderate to severe forms of the disease, according to a new report.
Investigators from South Carolina and Virginia reviewed the use of valbenazine and deutetrabenazine for tardive dyskinesia patients in order to discuss the efficacy, tolerability, dosing, drug interactions, and precautions associated with the treatment. In their analysis, the investigators studied existing literature.
Before the FDA approved valbenazine and deutetrabenazine for the treatment of tardive dyskinesia, the American Academy of Neurology recommended amantadine, gingko biloba, and clonazepam as treatment, the study authors said. VMAT-2 inhibitors were used off label for the treatment of tardive dyskinesia, but with FDA approval of valbenazine and deutetrabenazine, VMAT-2s are being used for their designated purposes.
Valbenazine and deutetrabenazine were evaluated in several trials, in which patients ranged in age from 18 to 85 years. The KINECT study’s first phase examining valbenazine measured the changes in patients from baseline to 6 weeks on the Abnormal Involuntary Movement Scale (AIMS). There were 3 treatment arms: placebo for 6 weeks; valbenazine 50 mg for 6 weeks; or valbenazine 100 mg daily for 2 weeks followed by 4 weeks of valbenazine 50 mg. The treatment groups saw a change of -3.3 on the AIMS scale while the placebo group change was -2.5 on the scale. Therefore, the investigators reported no significant change between the groups.
A subsequent study examined 80 subjects who received 50 mg valbenazine daily. Those patients saw an AIMS change of -.58, and nearly two-thirds of the patients were evaluated as “much improved” or “very much improved,” according to the study authors.
In KINECT 2, patients received 25 mg daily, which could be increased every 2 weeks up to 75 mg if the clinician deemed it appropriate in terms of efficacy and tolerability. Again, two-thirds of the patients were evaluated as “much improved” or “very much improved” and the AIMS change was -2.4.
KINECT 3 participants received either 40 or 80 mg daily valbenazine, although tolerability measures were not available from the investigators at the time the study authors went to print. AIMS score changes were significant, though: -3.0 in the 40 mg group and -4.8 in the 80 mg group.
The ARM-TD study looked at deutetrabenazine doses escalating from 12 mg to 48 mg daily across a six-week period. There was not much of a difference on the AIMS scale between placebo and treatment groups, but a perception of expectations of improvement may have played a factor, the study authors said.
A similar study, called AIM-TD, saw 4 groups of patients receive either 12, 24, 36, or 48 mg daily deutetrabenazine for 4 weeks. The middle groups saw significant reductions in AIMS scores, and nearly half of patients in those groups were rated “much improved” or “very much improved.” Again, there was a placebo effect of expectations of improvement, but the investigators suspected underlying psychological disorders may have prohibited the patients from assessing their own improvement.
The valbenazine KINECT studies did not have any significant adverse effects, treatment-related serious adverse events or suicidal ideation. The most common side effects were fatigue and headache in phase 2. The most common side effects from deutetrabenazine treatment included fatigue, insomnia, headache, diarrhea, somnolence, and akathisia.
The study authors noted there are no contraindications for valbenazine, but with deutetrabenazine, there is a boxed warning for increased risk for depression and suicidality in Huntington’s disease patients. The investigators also stated that caution is key for patients with prior suicide attempts or ideation, and it is important to monitor for emerging or worsening symptoms of depression and the like.
The paper, titled “Valbenazine and Deutetrabenazine for Tardive Dyskinesia,” was published in Innovations in Clinical Neuroscience.