From the FDA Drug Label
AUSTEDO XR and AUSTEDO may cause a worsening in mood, cognition, rigidity, and functional capacity AUSTEDO XR and AUSTEDO should be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias 5. 4 Neuroleptic Malignant Syndrome (NMS) A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with drugs that reduce dopaminergic transmission. 5. 5 Akathisia, Agitation, and Restlessness AUSTEDO XR and AUSTEDO may increase the risk of akathisia, agitation, and restlessness in patients with Huntington’s disease and tardive dyskinesia 5. 6 Parkinsonism AUSTEDO XR and AUSTEDO may cause parkinsonism in patients with Huntington’s disease or tardive dyskinesia.
The main concerns of Extrapyramidal Symptoms (EPS) with deutetrabenazine are:
- Parkinsonism: deutetrabenazine may cause parkinsonism in patients with Huntington’s disease or tardive dyskinesia
- Akathisia, Agitation, and Restlessness: deutetrabenazine may increase the risk of akathisia, agitation, and restlessness in patients with Huntington’s disease and tardive dyskinesia
- Neuroleptic Malignant Syndrome (NMS): a potentially fatal symptom complex that has been reported in association with drugs that reduce dopaminergic transmission, including deutetrabenazine 1
From the Research
Deutetrabenazine carries a risk of extrapyramidal symptoms (EPS) as a significant concern during treatment, and clinicians should monitor patients regularly for EPS, especially during dose adjustments and early treatment. These symptoms include akathisia (restlessness), parkinsonism (tremor, rigidity, bradykinesia), dystonia (sustained muscle contractions), and tardive dyskinesia (involuntary, repetitive movements) 2. The risk of EPS occurs because deutetrabenazine works by inhibiting vesicular monoamine transporter 2 (VMAT2), which reduces dopamine levels in the brain. This dopamine reduction, while therapeutic for conditions like Huntington's chorea and tardive dyskinesia, can disrupt the balance of neurotransmitters in the basal ganglia, leading to movement disorders. Patients with pre-existing movement disorders or those taking other dopamine-blocking medications are at higher risk. Some key points to consider when treating with deutetrabenazine include:
- Starting with low doses and titrating slowly can help minimize the risks of EPS 3
- Deutetrabenazine has a longer half-life and more consistent pharmacokinetics than its predecessor tetrabenazine, which may reduce the severity of EPS, but vigilance remains essential throughout treatment 2
- If EPS develops, dose reduction or discontinuation may be necessary 4
- The most common adverse reactions associated with deutetrabenazine include nasopharyngitis and insomnia, with number needed to harm (NNH) values of 50 and 34, respectively 2
- Clinicians should be aware of the potential for drug-drug interactions, particularly with inhibitors and inducers of cytochrome P450 (CYP) 2D6, and adjust dosing accordingly 5