Tardive Dyskinesia

The primary objective of this study is to evaluate the efficacy of NBI-1065890 compared with placebo for the treatment of tardive dyskinesia (TD) in adult participants.

This study will evaluate the efficacy of valbenazine on clinician- and patient-reported outcomes in participants with TD while receiving or after stopping a VMAT2 inhibitor.

The primary goal of this study is to investigate the efficacy of deutetrabenazine treatment of TD in this previously untreated patient population. Compare movement disorder deutetrabenazine treatment response in persons with IDD to response seen in patients without IDD treated with deutetrabenazine in other treatment settings (per literature review). Compare global deutetrabenazine treatment response with validated instruments. In addition, we plan to: * Assess the safety of deutetrabenazine in the treatment of TD in persons with IDD. * Assess change in Activities of Daily Living (ADLs) in persons with IDD and TD treated with deutetrabenazine, utilizing a validated ADL instrument. * Assess change in Quality of Life (QOL) in persons with IDD and TD treated with deutetrabenazine, utilizing a validated QOL instrument. * Assess caregiver burden with a validated caregiver burden instrument. In this study, 25 participants with IDD and TD will undergo Deutetrabenazine treatment for 24 weeks. The participants will be seen for a total of 5 visits: at baseline, and at follow up visits at 3 weeks, 6 weeks, 12 weeks, and 24 weeks. This study does not include a comparison group. Therefore, researchers will compare the response of the study participants to deutetrabenazine treatment with those from a previous reported work that resulted in the FDA approval of this medication. This will be an open-label, Phase 4 study.

\# Brief Summary (English Version) Tardive Dyskinesia (TD) is a hyperkinetic movement disorder induced by long-term use of dopamine receptor blockers and related drugs. Characterized by involuntary spasms or choreiform movements involving the tongue, lower face, jaw, and limbs (persisting for at least several weeks), TD causes irreversible neurological damage that persists even after discontinuing the causative drugs, significantly impairing patients' functional outcomes. rTMS is a non-invasive neuromodulation technique: time-varying currents in a coil generate magnetic fields that penetrate the scalp and skull to act on brain neurons, inducing depolarization, neural network activation, neurotransmitter release, metabolic changes, and gene expression, thereby producing physiological effects \[9\]. In recent years, rTMS has gained attention for treating movement disorders (e.g., Parkinson's disease, motor neuron disease, dystonia, essential tremor, Huntington's disease) due to its non-invasiveness, high safety, and repeatability. Studies have reported that rTMS can significantly improve motor symptoms in TD patients \[10, 11\]; however, existing research is limited by small sample sizes, conventional treatment parameters, large inter-individual variability, and unclear long-term efficacy. rTMS efficacy in TD is strongly influenced by parameters including stimulation targets, localization methods, sequences, and cycles. Optical navigation (using personalized MRI) is the most accurate and yields the best therapeutic effects, compared to manual localization or positioning caps . Regarding stimulation sequences, 1Hz and 20Hz rTMS have shown efficacy but with short-lived effects. Continuous theta-Burst Stimulation (cTBS)-a specialized rTMS mode that delivers rapid pulse trains mimicking endogenous theta-wave bursts-provides higher therapeutic doses in less time, enabling more durable efficacy and effectively reducing motor cortex excitability . Therefore, this study aims to investigate the effect of cTBS (under precise localization) on improving motor symptoms in patients with TD.

The statistical analysis of the collected data aims to reveal the many factors that influence patient involvement in clinical trials. Findings will be disseminated through conferences and scholarly papers to benefit all parties participating in clinical trials. These findings will help to shape the design of future clinical trials for people with tardive dyskinesia, as well as enhance recruiting techniques and retention rates.

To test the feasibility of studying effects of smoking cessation with varenicline on antipsychotic drug-induced neurological side effects, we propose a 12 week pilot study of smoking cessation treatment with varenicline in 10 schizophrenia or schizoaffective disorder patients who are actively smoking and have pre-existing TD while receiving stable doses of antipsychotics. Subjects will be followed after a 2 week baseline period to assess changes in smoking status and neurological symptoms using standardized rating scales. The aim is to examine clinically significant effects on antipsychotic-induced neurological side effects that may warrant further investigation.