Randomized controlled trial of deutetrabenazine for tardive dyskinesia

Abstract

Objective:To determine the efficacy and safety of deutetrabenazine as a treatment for tardive dyskinesia (TD).Methods:One hundred seventeen patients with moderate to severe TD received deutetrabenazine or placebo in this randomized, double-blind, multicenter trial. Eligibility criteria included an Abnormal Involuntary Movement Scale (AIMS) score of ≥6 assessed by blinded central video rating, stable psychiatric illness, and stable psychoactive medication treatment. Primary endpoint was the change in AIMS score from baseline to week 12. Secondary endpoints included treatment success at week 12 on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change.Results:For the primary endpoint, deutetrabenazine significantly reduced AIMS scores from baseline to week 12 vs placebo (least-squares mean [standard error] −3.0 [0.45] vs −1.6 [0.46], p = 0.019). Treatment success on CGIC (48.2% vs 40.4%) favored deutetrabenazine but was not significant. Deutetrabenazine and placebo groups showed low rates of psychiatric adverse events: anxiety (3.4% vs 6.8%), depressed mood/depression (1.7% vs 1.7%), and suicidal ideation (0% vs 1.7%, respectively). In addition, no worsening in parkinsonism, as measured by the Unified Parkinson's Disease Rating Scale motor subscale, was noted from baseline to week 12 in either group.Conclusions:In patients with TD, deutetrabenazine was well tolerated and significantly reduced abnormal movements.Classification of evidence:This study provides Class I evidence that in patients with TD, deutetrabenazine reduces AIMS scores.

Treatment of tardive dyskinesia with tetrabenazine or valbenazine: a systematic review

“…No studies are yet available that directly compare the effects of valbenazine and tetrabenazine in patients with TD. Another future science group www.futuremedicine.com VMAT2 inhibitor, deutetrabenazine, has been approved for the treatment of chorea in Huntington's disease, and more recently for TD, based on the results of two clinical trials (NCT02195700, NCT02291861) [45,46]. With publication of these controlled clinical studies for deutetrabenazine, a future meta-analysis of VMAT2 inhibitors specific for the treatment of TD may be possible.…”

Revisiting the Abnormal Involuntary Movement Scale

“…This potential for individual bias and less than optimal interrater variability may be minimized in studies that use central (offsite) video raters. For example, in the multicenter trials of valbenazine and deutetrabenazine, [29][30][31][32] each subject's AIMS examination was video recorded in a standardized manner at all study visits. Central raters who viewed these videos were blinded to treatment.…”

“…More discussion is needed between researchers and clinicians to ascertain if there are mutually acceptable standards of clinical relevance that could be used to interpret AIMS results across different clinical trials. With the recent publication of large and well-controlled clinical trials that showed substantial and statistically significant AIMS improvements with valbenazine and deutetrabenazine, [29][30][31][32] one line of inquiry would be to assess whether research diagnostic criteria such as Schooler-Kane 24 are adequately sensitive. In addition, TD researchers and clinicians may need to start thinking about optimal ways to adopt new technologies, such as wearable sensors, computerized video-based ratings, and smartphone-based monitoring of abnormal movements and other symptoms.…”

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“…Common side effects reported were sedation (13.8%), headache (6.9%), psychosis (1.7%), and suicidal ideation (1.7%). Deutetrabenazine is an effective and safe treatment option for those suffering from involuntary movement disorders [14].…”

“…In clinical studies of valbenazine, tetrabenazine and deutetrabenazine, the most common side effects were sedation, and akathisia [11][12][13][14]. Warnings and precautions for VMAT2 inhibitors include somnolence, QTc prolongation, and akathisia ( …”