EHDN international guideline: first-line treatment of chorea

“Drug treatment should be considered if chorea causes the patient distress or discomfort.” (opens the source at this quote in a new tab)
“Tetrabenazine is one of the first-line treatments for this symptom (Grade A)” (opens the source at this quote in a new tab)
“unless the patient suffers from not well-managed depression or suicidal thoughts.” (opens the source at this quote in a new tab)
“Deutetrabenazine may indeed be proposed as an alternative to tetrabenazine for the treatment of chorea in countries where the marketing authorization is already obtained, like in the USA.” (opens the source at this quote in a new tab)

AAN evidence-based guideline on chorea (retired 2022): recommendation

“If HD chorea requires treatment, clinicians should prescribe tetrabenazine (up to 100 mg/day), amantadine (300-400 mg/day), or riluzole (200 mg/day) (Level B) for varying degrees of expected benefit. Occurrence of adverse events should be discussed and monitored, particularly depression/suicidality and parkinsonism with tetrabenazine and elevated liver enzymes with riluzole.” (opens the source at this quote in a new tab)

AAN guideline status

“This guideline is retired.” (opens the source at this quote in a new tab)
“Retired on July 16, 2022.” (opens the source at this quote in a new tab)

German Neurological Society guideline: evidence for VMAT2 inhibitors and use of tetrabenazine

“The quality of data from RCTs is currently best for VMAT2 inhibitors” (opens the source at this quote in a new tab)
“The use of tetrabenazine (in combination or as monotherapy) is recommended if treatment with tiapride is either not tolerated or not efficacious.” (opens the source at this quote in a new tab)

MDS evidence-based review of treatments for Huntington's disease

“These data supported a likely effect of deutetrabenazine on motor impairment, chorea, and dystonia and of tetrabenazine on chorea.” (opens the source at this quote in a new tab)
“Data for therapeutic interventions in HD are limited and support only the use of VMAT2 inhibitors for specific motor symptoms.” (opens the source at this quote in a new tab)

Cochrane review of symptomatic treatments

“22 trials (1254 participants) were included.” (opens the source at this quote in a new tab)
“Only tetrabenazine showed a clear efficacy for the control of chorea. The remaining pharmacological interventions revealed no clear effectiveness.” (opens the source at this quote in a new tab)

HSG expert consensus: classes used for chorea in North American practice

“Despite the negative impact chorea can have on many aspects of day-to-day life, pharmacologic treatment remains underutilized in clinical practice.” (opens the source at this quote in a new tab)
“The two most common medication classes used to suppress chorea are vesicular monoamine transporter 2 (VMAT2) inhibitors and antipsychotics.” (opens the source at this quote in a new tab)

Tetrabenazine: FDA-approved indication and boxed warning

“XENAZINE is indicated for the treatment of chorea associated with Huntington’s disease.” (opens the source at this quote in a new tab)
“XENAZINE can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington's disease. Anyone considering the use of XENAZINE must balance the risks of depression and suicidality with the clinical need for control of chorea.” (opens the source at this quote in a new tab)

Tetrabenazine: label efficacy and functional outcomes in Study 1

“As shown in Figure 1, Total Chorea Scores for patients in the drug group declined by an estimated 5.0 units during maintenance therapy (average of Week 9 and Week 12 scores versus baseline), compared to an estimated 1.5 units in the placebo group. The treatment effect of 3.5 units was statistically significant. At the Week 13 follow-up in Study 1 (1 week after discontinuation of the study medication), the Total Chorea Scores of patients receiving XENAZINE returned to baseline.” (opens the source at this quote in a new tab)
“In general, measures of functional capacity and cognition showed no difference between XENAZINE and placebo.” (opens the source at this quote in a new tab)

Tetrabenazine: depression and sedation in the placebo-controlled trial

“In a 12-week, double-blind, placebo-controlled study in patients with chorea associated with Huntington’s disease, 10 of 54 patients (19%) treated with XENAZINE were reported to have an adverse event of depression or worsening depression compared to none of the 30 placebo-treated patients.” (opens the source at this quote in a new tab)
“Sedation is the most common dose-limiting adverse reaction of XENAZINE.” (opens the source at this quote in a new tab)

Tetrabenazine: TETRA-HD randomized trial

“The authors randomized 84 ambulatory patients with HD to receive TBZ (n = 54) or placebo (n = 30) for 12 weeks.” (opens the source at this quote in a new tab)
“There were five study withdrawals in the TBZ group and five serious adverse events (SAEs) in four subjects (drowning suicide, complicated fall, restlessness/suicidal ideation, and breast cancer) compared with one withdrawal and no SAEs in the placebo group.” (opens the source at this quote in a new tab)

Deutetrabenazine: FDA boxed warning and label efficacy

“AUSTEDO XR and AUSTEDO can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington’s disease.” (opens the source at this quote in a new tab)
“Total Maximal Chorea Scores for patients receiving AUSTEDO improved by approximately 4.4 units from baseline to the maintenance period (average of Week 9 and Week 12), compared to approximately 1.9 units in the placebo group. The treatment effect of -2.5 units was statistically significant (p<0.0001).” (opens the source at this quote in a new tab)

Deutetrabenazine: First-HD randomized trial

“Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002).” (opens the source at this quote in a new tab)
“Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety.” (opens the source at this quote in a new tab)

Valbenazine: FDA boxed warning and label efficacy

“VMAT2 inhibitors, including INGREZZA and INGREZZA SPRINKLE, can increase the risk of depression and suicidal thoughts and behavior in patients with Huntington’s disease.” (opens the source at this quote in a new tab)
“The mean change in Total Maximal Chorea scores for patients receiving INGREZZA improved by 4.6 units (LS mean) from baseline to the end of the treatment period (average of Week 10 and Week 12), compared to 1.4 units in the placebo group. The treatment effect of -3.2 units was statistically significant (p<0.0001)” (opens the source at this quote in a new tab)

Valbenazine: parkinsonism in Huntington's disease

“Drug-induced parkinsonism has the potential to cause more functional disability than untreated chorea for some patients with Huntington’s disease.” (opens the source at this quote in a new tab)

Valbenazine: KINECT-HD randomized trial

“Of 128 randomly assigned participants, 125 were included in the full-analysis set (64 assigned to valbenazine, 61 assigned to placebo) and 127 were included in the safety-analysis set (64 assigned to valbenazine, 63 assigned to placebo).” (opens the source at this quote in a new tab)
“No suicidal behaviour or worsening of suicidal ideation was reported in participants treated with valbenazine.” (opens the source at this quote in a new tab)

HDSA physician's guide: indications for pharmacologic treatment of chorea

“Symptoms that indicate the need for possible pharmacologic management of chorea include muscle pain, frequent dropping of items, repetitive injuries, falls associated with chorea of the trunk and limbs, poor sleep, and weight loss.” (opens the source at this quote in a new tab)