Pilot Study to Evaluate Pimavanserin for the Treatment of Motor and Behavioral Symptoms of Tourette Syndrome

Abstract

BackgroundBackground: Pimavanserin is a serotonin 2A receptor inverse agonist and antagonist used for the treatment of hallucinations and delusions in Parkinson's disease psychosis. Numerous studies support a modulatory role of serotonin in Tourette syndrome (TS). Objectives Objectives: To determine whether or not pimavanserin affects TS symptoms. Methods Methods: In this open-label study of TS adult patients, pimavanserin was titrated to 34 mg/day over 1 week and continued for an additional 7 weeks followed by a 2-week washout. Tic severity, the primary outcome measure, was assessed by the Yale Global Tic Severity Scale Total Tic Severity score (YGTSS-TTS). Secondary outcome measures included changes in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Tourette Syndrome Clinical Global Impression of Change (TS-CGIC), the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII), and the Gilles de la Tourette Syndrome -Quality of Life scale (GTS-QOL). ResultsResults: We enrolled 12 patients, but 2 dropped out after week 2 due to non-serious side effects. In the 10 patients, mean (standard deviation (SD)) age 34 (12.9) who completed the study the mean (SD) baseline YGTSS-TTS was 34 (9.3). This decreased by 3.6 (4.9) points at week 8, a 12% reduction in tic severity (P = 0.03). This improvement is small and may not be clinically important. Significant improvement was noted in the TS-CGIC, TS-PGII and GTS-QO. No serious adverse events were reported. Conclusions Conclusions:The results of this study suggest that pimavanserin is safe and associated with improvement in motor and non-motor TS symptoms. These findings warrant further study by a larger, placebo-controlled, trial.Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor and phonic tics that frequently cooccur with a variety of behavioral and psychiatric problems including obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). [1][2][3] Over the years the results of numerous drug trials, neurophysiological studies, imaging analyses, and examination of human samples (eg, blood, urine, cerebrospinal fluid, brain tissue) have led to several hypotheses regarding the neurochemical abnormalities in TS. 4 The most widely accepted theory suggests dopaminergic dysfunction, however, imbalances in serotonergic, GABAergic, noradrenergic, glutamatergic, and cholinergic systems have been also implicated. [5][6][7] Currently pimavanserin, a serotonin 2A receptor inverse agonist and antagonist, is approved by the United States Food and Drug Administration for the treatment hallucinations and delusions associated with Parkinson's disease psychosis. 8 With growing evidence that serotonin may serve a modulatory role in TS and that patients with TS have higher serotonin receptor binding affinity, we sought to determine whether pimavanserin would have an effect on motor and behavioral aspects of TS. MethodsThis was an open label, proof-of-principle, pilot study to evaluate pimavanserin in the treatment ...

Tourette syndrome research highlights from 2021

“…Here too, larger, placebo-controlled trials are warranted. 96 Neurosurgery Several important papers have been published in 2021, which provide interesting insights for clinical management of these patients and also for the better understanding of the neural bases and brain targets involved in deep brain stimulation (DBS) effects.…”