番茄社区

VANCOUVER -- Individuals experiencing movement disorders of the face and limbs caused by antipsychotic drugs got substantial relief from the investigational agent valbenazine, researchers reported here.

In a phase III, randomized clinical trial, patients on an 80-mg dose of valbenazine achieved a 3.2-point reduction in the Abnormal Involuntary Movement Scale (AIMS) compared with a 0.1-point reduction in the scale which measures tremors among patients who were assigned assigned to placebo (P<0.0001), said , of the University of South Florida Morsani College of Medicine.

At the annual meeting of the American Academy of Neurology, Hauser reported that patients on a 40-mg dose also achieved a statistically significant reduction in AIMS scores -- 1.9 points (P=0.0021). The mean baseline score on the AIMS scale was 10.

For a secondary endpoint, the Clinicians Global Index of Change-Tardive Dyskinesia (CGI-TD), patients on treatment with the higher dose showed a trend to improvement (P=0.0560) as did patients on the lower dose of the drug (P=0.0742).

"Once-daily valbenazine improved tardive dyskinesia severity," Hauser told 番茄社区. "Treatment with valbenazine was well tolerated, with no notable safety issues."

About 1% of the population experiences schizophrenia-related disorders, requiring treatment with antipsychotics, but chronic dopamine receptor blocking agents can cause disturbing involuntary movements of the jaw, tongue, lips, face, trunk, and limbs which can cause patients to withdraw socially.

"Tardive dyskinesia can persist even after drug discontinuation," Hauser said. To combat these movement disorders which can in some cases lead to drug discontinuation and thus to psychotic relapses, researchers developed valbenazine, a highly selective inhibitor of vesicular monoamine transporter-2 or VMAT2.

In the KINECT 3 study, 78 patients were assigned to placebo; 76 were assigned to valbenazine 40 mg and 80 patients were assigned to 80 mg once-daily valbenazine. After the 6-week randomized phase of the trial, patients on placebo and those on valbenazine were invited to continue open-label treatment through 48 weeks, followed by a 4-week follow-up period.

"Tardive dyskinesia is not one of the conditions that we talk about a lot," , vice chair of the AAN scientific committee and associate professor of neurology at Massachusetts General Hospital/Harvard Medical School, Boston, told 番茄社区. "This is a behind-the-scenes aftermath of the treatment -- in a large sense it is iatrogenic.

"If we can help patients become compliant with their medications it would be a globally huge event," she said. "If you have these persistent, intrusive, uncontrollable movements of your lips and tongue, it may be just as disruptive to your lifestyle as if you were having problems with your arm or hand. So whatever points we can knock off of the AIMS scale, I would want that.

"These movements can be embarrassing, and even if they are still employable, they may not be able to face the public. These movements also interfere with nutrition, in feeding oneself and in other social activities," she said.

Trialists at 64 sites enrolled patients, about 66% who were diagnosed with schizophrenia; the rest had other conditions often treated with antipsychotics such as bipolar disorder and severe depression. About 86% of patients were currently receiving stable doses of concomitant antipsychotic medications. About 77% of medications were in the so-called atypical class.

Hauser reported that adverse events were similar at both doses and with placebo. The most commonly reported adverse event was somnolence, reported by 5% of the patients on the 80-mg dose of valbenazine, 4% of the patients on the 40-mg dose, and 4% of patient who had been assigned to placebo. He said 3% of subjects discontinued due to treatment-emergent adverse events in the 40-mg group and in placebo patients; 4% discontinued in the 80-mg arm.