Q&A: Study supports use of VMAT2 inhibitors to treat tardive dyskinesia

Researchers recently found that the pharmacokinetic properties of vesicular monoamine transporter 2 inhibitors may play a role in the treatment of tardive dyskinesia.

Healio Neurology spoke with Eiry W. Roberts, MD, Neurocrine Biosciences chief medical officer, about tardive dyskinesia and options for managing it.

Healio: Please briefly describe tardive dyskinesia.

Eiry W. Roberts

Roberts: Tardive dyskinesia (TD) is an involuntary movement disorder that is characterized by uncontrollable, abnormal and repetitive movements of the face, torso and other body parts. TD is associated with prolonged use of certain mental health medications (antipsychotics) that are used to treat bipolar disorder, depression, schizophrenia and schizoaffective disorder. Other prescription medicines used to treat upset stomach, nausea and vomiting may also cause TD.

Healio: What kind of treatments are available for this?

Roberts: There are two FDA-approved treatment options for TD. These treatments are called vesicular monoamine transporter2 (VMAT2) inhibitors, which are thought to reduce extra dopamine signaling in the brain. Ingrezza (valbenazine, Neurocrine) [available in capsule form] is a novel VMAT2 inhibitor that selectively targets VMAT2. It was approved in 2017 and is the only once-daily treatment option for adults with TD.

Healio: Are there different types of approaches for treating this condition?

Roberts: The American Psychiatric Association Practice 2020 Guidelines recommend that patients who have moderate to severe or disabling TD associated with antipsychotics be treated with VMAT2 inhibitors.

To determine optimal treatment, it’s necessary for clinicians to assess the possible presence and severity of TD, in addition to assessing the patient’s awareness of and perspective on the impact of symptoms. It’s important to note that anticholinergic medicines, such as benztropine, are approved to treat other movement disorders, but they are not approved to treat TD.

Healio: Is one preferred over the other? Why?

Roberts: Valbenazine and deutetrabenazine have both been shown in well-controlled trials to be safe and effective for the treatment of TD. However, a recent Clinical Pharmacology in Drug Development study found that the differences in their metabolic and pharmacodynamic profiles may have important clinical implications.

In particular, valbenazine has a unique pharmacological profile and is metabolized to a single active HTBZ [dihydrotetrabenazine] metabolite that is a selective inhibitor of VMAT2 with no observed off-target activity.

Healio: Is there anything else that is important to note?

Roberts: Even mild movements from TD could have emotional and social consequences for patients, so it’s critical that patients are screened by a health care professional and a treatment plan is discussed for those diagnosed.

Reference:

Brar S, et al. Clin Pharmacol Drug Dev. 2023;doi:10.1002/cpdd.1205.