• The effectiveness of Ingrezza improves with time, with maximal effectiveness reported at around 32 weeks.
• Effectiveness is usually determined by a significant change from baseline in either the Abnormal Involuntary Movement Scale (AIMS) or the Clinical Global Impression–Tardive Dyskinesia (CGI-TD) scale.
• Trials consistently report over 61% of participants as “much improved” or “very much improved” after 4 to 6 weeks treatment with Ingrezza 50mg to 80mg according to their CGI-TD score. Changes in baseline with AIMS range from -2.4 to -5.8.
• Symptoms of tardive dyskinesia return within four weeks of discontinuing Ingrezza.

Ingrezza (valbenazine) is an oral medication that may be used to treat symptoms of tardive dyskinesia (TD) in adults. Ingrezza will not cure TD.

Ingrezza belongs to a class of medicines called vesicular monoamine transporter 2 (VMAT2) inhibitors.

Some improvement in TD symptoms may be noticed in as little as 2 weeks; however, it usually takes at least 6 to 8 weeks for significant effects to be seen. Maximal benefits were experienced 32 weeks into treatment. Symptoms of TD returned to baseline levels within four weeks of discontinuing Ingrezza.

Results from trials investigating the effectiveness of Ingrezza (valbenazine) using either tools such as the Abnormal Involuntary Movement Scale (AIMS) or the Clinical Global Impression–Tardive Dyskinesia (CGI-TD) scale were:

• KINECT study: Although the change in symptoms from baseline with valbenazine were not significantly different than placebo after 4 weeks treatment, 61% of participants who continued with valbenazine 50mg were assessed to be “much improved” or “very much improved” according to their CGI-TD score (-5.8 change from baseline with AIMS)
• KINECT 2 study: 67% of patients were assessed as very much improved or much improved according to CGI-TD score after 6 weeks of treatment with valbenazine (25mg to75mg). The AIMS change from baseline was statistically significant at -2.4
• KINECT 3 study: participants received either a placebo, valbenazine 40mg daily or valbenazine 80mg daily for six weeks. Although symptoms of TD reduced in both treatment groups only the 80mg treatment group was statistically significant (change in AIMS scores of valbenazine vs. placebo: -3.2 vs. -0.1). There were no statistically significant differences among groups according to the CGI-TD score. Those who continued treatment for a further 42 weeks reported statistically significant reductions in their mean AIMS score (-3.0 in the 40mg group and -4.8 in the 80mg group) as well as reductions in the CGI-TD.

The most common adverse events of Ingrezza were fatigue, sleepiness, constipation, dry mouth, headache, nausea, and vomiting.

The AIMS test is used to detect TD and to follow the severity of a patient's TD over time. The CGI-TD takes into account all available information, such as a patient's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the patient's ability to function.

How does Ingrezza work?

Experts aren’t sure how Ingrezza works but suspect it blocks a protein transporter called vesicular monoamine transporter 2 (VMAT2), that is responsible for regulating the uptake of monoamine neurotransmitters such as dopamine, noradrenaline, and serotonin from the cytoplasm of the cell into the synaptic vessels.

Synaptic vessels store neurotransmitters for release into the synapse (the space between two nerves). These neurotransmitters have various functions within the body but dopamine in particular plays a role in movement as well as pleasure, motivation, and learning. Abnormal functioning of dopamine is thought to be a cause of TD.

By blocking VMAT2, Ingrezza reduces the uptake of monamines, such as dopamine, causing a decrease in symptoms of TD.

What is tardive dyskinesia (TD)?

TD is a term used to describe a cluster of abnormal, involuntary movements, especially of the lower face, that develop after exposure to antipsychotics or other medications that block dopamine receptors, such as metoclopramide.

The abnormal movements include tongue thrusting, repetitive chewing, jaw swinging, lip-smacking, and/or facial grimacing. Older generation (typical) antipsychotic medications, such as haloperidol, trifluoperazine, or fluphenazine are the most common causative agents.

The condition may be reversible if recognized in the earliest stages, by stopping the causative agent, but may be permanent. On occasion, if the anti-psychotics are stopped after the tardive dyskinesia has been present for a long period, the condition may become significantly worse.